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Immuno PPT Flashcards Unit 1 Too many leukocytes is called Too few leukocytes is called About how many percent of all leukocytes are basophils? What color dye does the cytoplasm of basofils absorb? These granules of the basophils secrete What is the role of histamines? What interfere with the function of basophils? What is a Mast Cell? About how many percent of all leukocytes are eosinohils? What color dye does the cytoplasm of eosinofils absorb? Eosinophils cells play roles in: The most numerous WBCs are the What color dye does the cytoplasm of neutrofils absorb? Which WBCs respond first to infection? What is the main role of the netrophils? The nucleus of the neutrophils has how many lobes? How do neutrophils contribute to immunity? How is a process of engulfing bacteria and foreign bodies called? What do the lysosomes do to the invaders? When a bacterium has a capsule, it makes it hard to phagocytize, so the neutrophil requires what? What do some bacteria have evolved as a defense against phagocytosis? Can the neutrophil or macrophage engulf bacterias with a capsule around them? How can neutrophil phagocytize encapsulated bacteria? The process of facilitation of phagocytosis is called When an invading bacteria has the antibody leukophilia leukopenia 0.5% The basic pH dye, which is blue, so they are called basophils (“basic dye lovers”). histamines Causing vasodilation; more WBCs can get to the infection site Antihistamines A type of basophil that is in the tissues. 1-4% Granules in cytoplasm absorb the pink dye called eosin, so they are called eosinophils (“eosin dye lovers”). Ending allergic reactions, parasitic infections Neutrophils Granules in cytoplasm do not absorb either the basic or the eosin dye, so they are called neutrophils. Neutrophils Phagocytize and destroy bacteria; Also destroy bacterial toxins in body fluids 2-6 mainly by engulfing bacteria and foreign bodies (thorns, dirt, etc) phagocytosis They release the contents of their lysosomes onto the invader, dissolving it. opsonization by antibodies a slippery capsule around them No When an antibody attaches to this type of bacteria, the neutrophil can now grab onto the antibody like a handle, enabling it to phagocytize the bacteria opsonization antigen-antibody complex 1 Immuno PPT Flashcards Unit 1 attached to its cell membrane, the entire structure is called If a bacterium does not have a capsule, how can the neutrophil destroy it? How can the antibody destroy the bacterium by itself? The neutrophil and antibody work best together when About how many percent of all leukocytes are monocytes? What are the monocytes do? What is the difference between monocytes and neutrophils? Monocytes use what for opsonization? When monocytes leave the bloodstream and enter the tissues, they are called What characterize the dendritic cells? What is the purpose of saving a piece of the bacterium to present to a T-Cell? Why are the basophils, eosinophils, neutrophils, and dendritic cells classified as granulocytes? Why are the monocytes not granulocytes? Except for dendritic cells, they are all descendants from the same precursor cell called All of these WBCs are called The lymphocytes and dendritic cells are descended from a different precursor, so they are called How are the lymphoid cells classified? Which WBCs are the most numerous in the bloodstream? Which WBCs are the most numerous in the tissues? How long do neutrophils live? How long do Monocytes/Macrophages live? How long do lymphocytes live? What’s the Difference between Neutrophils and Monocytes/Macrophages? without opsonization by popping the cell membrane a capsule is present about 5% Like neutrophils, they phagocytize (eat) bacteria, old cells, and foreign bodies. Monocytes have more types of lysosome enzymes than neutrophils so they are better at killing difficult pathogens. antibodies Macrophages Dendritic cells save a piece of the bacterium to present to a T-Cell. To activate a humoral response. They have granules in their cytoplasm. The monocytes do not have granules in their cytoplasm a myeloid cell myeloid cells lymphoid cells T-Cells (three types; Helpers, Killers, and Suppressers) B-cells (three age groups; virgins, plasma cells, memory cells) Dendritic Cells (these are also granulocytes) There are 10x more neutrophils in the bloodstream than monocytes/Macrophages There are more macrophages in the tissues of the body. They are everywhere! only a few days few months Lymphocytes live for years Monocytes/Macrophages are larger and slower than neutrophils, but they can phagocytize 2 Immuno PPT Flashcards Unit 1 What’s the Difference between Neutrophils and Monocytes/Macrophages and Dendritic cells? Neutrophils , macrophages, and dendritic cells mainly function by Lymphocytes are mostly needed to kill off what? All WBC’s secrete chemicals to do what? Unlike neutrophils, macrophages have what? What are the surface receptors? How do the macrophages kill the bacteria? What are the dendritic cells do? What are the dendritic cells do with the pieces of the bacteria’s cell membrane? Dendritic cells present these pieces to T cell will present these pieces to When the B lymphocyte feels the shape of the bacteria pieces is called About how many percent of all leukocytes are lymphocytes? The most important cells of the immune system are How many types of lymphocytes are there? What is the function of the two types of lymphocytes? Both types of lymphocytes can only act against What are two main classes of lymphocyte? B cells originate in the When it has not been presented to, it is called a After presentation, it will mature into What is a mature plasma cell do? After the war is over, the plasma cell will mature into a T cells originate in the What are the T-cells do? larger organisms and more of them Neutrophils and macrophages just phagocytize bacteria until they die. Dendritic cells phagocytize and then take pieces of the dead bacteria and present them to lymphocytes so a larger immune response can occur phagocytizing bacteria (not viruses) body cells infected by viruses To recruit more white blood cells to the site. surface receptors "recognize" the surface of the pathogen’s cell membrane Macrophages phagocytize the bacteria, pop their lysosomes onto it, and dissolve it Dendritic cells also do phagocytize the bacteria, pop their lysosomes onto it, and dissolve it, except they save some pieces of the bacteria’s cell membrane They places these pieces of bacteria on its own cell membrane, and finds a lymphocyte to present it to T cell lymphocytes B cell lymphocytes “antigen presentation” 20–45% Lymphocytes 2 one makes antibodies and the other engages in direct combat with viruses and can also kill our body cells infected with viruses a specific foreign molecule (antigen) B cells and T cells bone marrow virgin B cell plasma cells fights infection by producing antibodies “queen” , called a Memory Cell thymus gland They attack foreign cells directly (including 3 Immuno PPT Flashcards Unit 1 B cells – start as Plasma cells secrete What kills the attacking cell? In which three ways antibodies attack? organ transplants!). They can also kill viruses by killing the infected host cell. virgin cells antibodies the plasma cell’s antibodies -They attach to bacteria and pop the cell membrane -They attach to encapsulated bacteria to help neutrophils and macrophages to phagocytize them. -They agglutinate (clump all over the bacteria, binding their receptor sites so they cannot cause harm) Mononucleosis When Epstein Barr virus attacks B lymphocytes, the disease is called How is mononucleosis characterized? inflammation of lymph vessels (lymphangitis) In mononucleosis, how do infected lymphocytes Infected lymphocytes have a characteristic appear under the microscope? scalloped edge where they touch RBC’s T cells – coordinate the immune response by recruiting other white blood cells How can T-cells destroy bacteria? They can directly destroy bacteria by popping their cell membrane T cells can also directly destroy foreign cells by organ transplants popping the cell membrane, so who are at risk? T-cells can also kill a host body cell that has become infected with viruses Do the T-cells need to phagocytize the invading No, they do not cell? After the T-cells kill the cell, what will happen the macrophages dissolve the debris with the debris? Do the T-cells need the assistance of No, they do not antibodies? Which cells attack organ transplants? T cells Immunosuppression drugs are designed to inhibit the action of T cells T cells are attacked by the HIV (AIDS) virus The thymus gland secrets certain hormones The hormones secreted by the thymus gland T cells to become immunocompetent (makes cause the cells mature and start to work) What are the main types of T cells? Natural Killer cells, Helper T cells, Suppressor T cells What is the role of the Natural Killer cells? Go out and directly kill bacteria or infected host cells What is the role of the Helper T cells? Release chemicals called “cytokines” to call in 4 Immuno PPT Flashcards Unit 1 What is the role of the Suppressor T cells? They can react to the same pathogen faster, the next time it invades because The study of the reactions of a host when foreign substances are introduced into the body is defined as A foreign substance that induces such an immune response in a host is The condition in a host of being resistant to infection is defined as Edward Jenner found what? The procedure of injecting powdered scabs from someone with cowpox lesions was known as What is the Latin terminology for “vacca” ? The phenomenon in which closure to one agent produces protection against another agent is known as Who was Louis Pasture? What is attenuation? An attenuated substance is Louis Pasteur applied this same principle of attenuation to the prevention of Metchnikoff, a Russian scientist, observed that The process where white blood cells attempt to destroy foreign objects by eating them is Cellular immunity involves more white blood cells of all types to join in the war. They also present the macrophage’s antigen to a B cell, which causes it to produce antibodies against that particular bacteria. Stop the immune process when it is over, and also "tell" some plasma cells to "remember" how to destroy that specific pathogen. Memory B-cells already have the proper antibodies stored up for that pathogen. Immunology An antigen Immunity that milkmaids who were exposed to cowpox had immunity to smallpox vaccination “cow”. cross-immunity He worked with the bacteria that cause chicken cholera. He accidentally found that old cultures would not cause disease in chickens. Subsequent injections of more virulent organisms had no of effect on the chickens that had been previously exposed to older cultures. In this manner, the first attenuated vaccine was discovered. Change; may occur through heat, aging, or chemicals one that has been weakened, and it does not cause disease. Rabies foreign objects introduced into transparent starfish larvae became surrounded by white blood cells that attempted to destroy the foreign objects by eating them. phagocytosis direct cell-to-cell interaction 5 Immuno PPT Flashcards Unit 1 Humoral (“blood”) immunity involves Who linked the two theories by showing that the immune response involved both cellular and humoral elements? What did Wright observe? The humoral, or circulating, factors are called These serum factors include specific proteins known as These serum factors included also non-specific factors called The ability of the host to resist infection by means of normally present body functions is called Is prior exposure required for innate immunity? Does the response change with subsequent exposures? Innate immunity is the same as calling it Characterized by specificity for each individual pathogen, or microbial agent, and the ability to remember a prior exposure, which results in an increased immune response is This refers to the action of the Adaptive immunity is the same as calling it Which immune responses are required for a healthy host? The two types of Adaptive Immunity are Both types of immunities are acquired how? The natural defense system can be considered as being composed of which two parts? Which system attempts to prevent entry of pathogens? What are the structural barriers that prevent most infectious agents from entering the body? Other external defenses include (This includes monocytes/macrophages, neutrophils, and Killer T-lymphocytes. It can include eosinophils and basophils as well) Antibodies (This refers to the action of B-lymphocytes) An English physician named Wright that certain humoral, or circulating, factors acted to coat bacteria so that they became more susceptible to ingestion by phagocytic cells opsonins antibodies acute-phase reactants Innate immunity No, they are nonspecific and are the same for all pathogens or foreign substances to which one is exposed. The response does not change; the phagocytes and Killer T cells are just doing their jobs by identifying and eliminating pathogens that might cause infection. cellular immunity Adaptive immunity B-lymphocytes humoral immunity Both innate and adaptive Active and Passive Immunity Naturally and artificially the external defense system and the internal defense system External system unbroken skin and the mucosal membrane surfaces Lactic acid in sweat and fatty acids from sebaceous glands to keep skin acidic and inhibit 6 Immuno PPT Flashcards Unit 1 What clear away 90% of the deposited material in the respiratory tract? What helps to remove many pathogens in the renal system? What plays role in preventing invasion of pathogens in the female genital tract? What halts bacterial growth in the digestive tract? Lysozyme is an enzyme found in tears and saliva and it attacks the cell walls of bacteria, especially Gram…? Why is normal flora present on the body? bacteria from growing. mucous secretions and cilia The flushing action of the urine, plus its slight acidity Lactic acid keeps the vagina acidic, preventing invasion of pathogens acidity of the stomach -positive to keep pathogens from establishing themselves Which defense system deals with pathogens that The Internal defense system gain entry? What play essential parts in the internal defense Both cells and soluble factors system? The internal defense system is designed to recognize molecules that are unique to infectious organisms. This typically involves recognizing what? a carbohydrate such as mannose that is found in bacteria and not on human cells In internal defense system WBSs seek out and destroy the invading cells Phagocytosis is enhanced by soluble factors acute-face reactants called Both internal and external defense systems phagocytosis promote what? Acute phase reactants are produced primarily by hepatocytes (liver cells) within 12-24 hours in response to cytokines Chemicals that call other white blood cells to Cytokines the area of infection are called Cytokines are produced by monocytes and macrophages during the inflammatory response Cytokines are released, not only from infection, injury to the tissues but also by The main cytokines are: Interleukin 1 beta (IL-1b), Interleukin -6 (IL-6) and Tumor necrosis Factor – alpha (TNF-a) Acute phase reactants include C-reactive protein Serum amyloid A The complement system Mannose-binding protein Alpha-1 antitrypsin Haptoglobin Fibrinogen 7 Immuno PPT Flashcards Unit 1 A substance found in small amounts in the serum, thought to be an antibody to the polysaccharide capsule of pneumococcal bacteria is When is CRP increases rapidly? Within 48 hours after infection, the levels of CRP can increase with how much? How will the levels decline? Elevated CRP levels are found in CRP acts like an antibody and is capable of CRP binds to specific receptors on Because the levels of CRP rise and then decline so rapidly, it is the most widely used indicator of CRP is a nonspecific indicator of disease or trauma, but it can be used to CRP is also used to monitor what? How can CRP used to monitor malignancy and organ transplantation rejection? An increased level of CRP is also a significant risk factor for Another major protein whose concentration can rise 1000 fold is Where can Serum amyloid A found? What is the role of Serum amyloid A? By removing cholesterol from macrophages at the site tissue injury, serum amyloid A contributes to the Serum amyloid A levels increases in what types of infections? A series of serum proteins that are normally present and whose function is mediation of inflammation refers to How many complement proteins are there? Complements are activated by Ceruloplasmin C-reactive protein (CRP) after infection, surgery, or trauma Levels can rise to 1000 fold The levels decline rapidly when the stimulus stops bacterial infections, rheumatic fever, viral infections, malignant diseases, tuberculosis, and after a heart attack optimization, agglutination, precipitation, and activation of complement monocytes, macrophages and neutrophils, which promotes phagocytosis acute inflammation follow a disease process and observe the response to treatment of inflammation and infection malignancy and organ transplantation rejection A rise in its level may mean a return of malignancy, or beginning of organ rejection myocardial infarction and ischemic stroke in people who have no previous history of cardiovascular disease Serum amyloid A It is made in the liver and circulates in the plasma it is associated with HDL cholesterol, and is thought to play a role in metabolism of cholesterol cleaning up of the area more in bacterial infection than in viral infections Complement 9 antibodies 8 Immuno PPT Flashcards Unit 1 When are the complement proteins activated by antibodies? Several additional proteins are involved in the The alternate pathway is triggered by The major functions of complement are Which protein is able to recognize foreign carbohydrates such as mannose which are found on bacteria, yeast, viruses, and parasites? How does MBP acts? Where can MBP found? What happens when MBP binds to the sugar? in an event called classical complement cascade alternate pathway microorganisms opsinization, chemotaxis, and lysis of cells Mannose-binding protein (MBP) MBP acts as an opsonin MBP is widely distributed on mucosal surfaces throughout the body It activates the complement cascade and helps to promote phagocytosis recurrent yeast infections Alpha-1 antitrypsin (AAT) Lack of MBP is associated with A general Plasma inhibitor of proteases released from leukocytes, especially elastase, which is an enzyme that degrades elastin and collagen is called Because of its activity in chronic pulmonary Lung tissue disease, what is damaged? During an inflammatory response, what does It counteracts the effects of neutrophil invasion AAT do? AAT also regulates what? Expression of cytokines such as TNF-a, IL-b, and IL-6. AAT deficiency can result in premature emphysema in smokers since uninhibited proteases remain in the lower respiratory tract, leading to destruction of cells in the lungs AAT can also react with any serine protease, such as those generated by the complement cascade Once bound to AAT, what happens to the the protease is completely inactivated protease? Haptoglobin’s job it to bind to what that is free hemoglobin released when RBCs are lysed i Once haptoglobin is bound, the complex is Kupffer cells in the liver ingested rapidly by Why are the Kupffer cells ingest the complex? Once bound, the complex is ingested rapidly by Kupffer cells in the liver so the kidneys are not damaged by trying to filter out that large protein What do the Kupfer cells prevent? the loss of iron Where is the complex sent? it can be sent to the bone marrow to be recycled Haptoglobin also protects against oxidative damage that the free hemoglobin would cause The rise of haptoglobin in the plasma is due to liver making too much the What does the rise of haptoglobin indicates? inflammation, stress, or tissue necrosis 9 Immuno PPT Flashcards Unit 1 Early on in the inflammatory response, haptoglobin levels may drop because of What levels must be evaluated along with the other acute phase reactants? Which one is the most abundant of the coagulation factors in plasma? What does fibrinogen do? Why is the formation of fibrin blood clot important? Fibrinogen also serves to promote Increased levels of the fibrinogen contribute to The main copper-transporting protein in human plasma is How is Ceruloplasmin oxidizes iron? Fe3+ releases iron from ferritin, so it can bind to what? What happen to RBC’s that are old? After the RBC’s are trapped, what happen to them? Hemoglobin is made from These three segments of hemoglobin are The globin chains (proteins) are broken down into Amino acids are used for In the hemoglobin what are the globins? The heme units are the What is essential to nearly all cells but also is quite toxic? Iron is essential for its role in intravascular hemolysis; consequently masking the protein’s behaviour as an acute phase reactant Plasma levels Fibrinogen it forms the fibrin blood clot A clot stops bleeding and also creates a barrier that helps prevent the spread of microorganisms further into the body aggregation of RBCs an increased risk for developing coronary artery disease, especially in women Ceruloplasmin from Fe2+ to Fe3+, which releases iron from ferritin transferrin their cell membranes become irregular and they become trapped in the reticular fibers in the spleen A macrophage engulfs it, and breaks down the hemoglobin heme (a porphyrrin ring with iron in the center), and globin chains detached from each other and liberated amino acids (the building blocks of proteins) synthesis of any other proteins wherever they are needed The alpha and beta chains the porphyrin rings Iron oxidation-reduction reactions needed for metabolism Where is iron’s toxicity comes from? from its propensity to form oxygen radicals that damage cells. What happen when hemoglobin is broken the iron (Fe+2) is released into plasma down? (ceruloplasmin is needed for that). Which protein binds to iron? apoferrin After apoferrin binds to the iron, the apoferrin is transferrin called What does transferring do? takes the iron into cells that can use or store it 10 Immuno PPT Flashcards Unit 1 The iron is stored in most body cells as A depletion of ceruloplasmin is found in what disease? Wilson’s disease, which is characterized by Copper accumulates where in the body? Normally, the circulating copper is found where? Cellular defense mechanisms include which 6 main types of WBCs? About how many percent of all WBCs are basophils? How big are the basophils when comparing them to the other granulocytes? The granules of the basophils contain What are histamine, heparin, and eosinophilic chemotactic factor-A do? Histamine causes what? Vasodilation of the blood vessels allows What is Heparin? Which immunoglobin is formed in allergic reactions? What is the role of IgE? What happens when IgE binds to basophil cell membranes? What is a Mast Cell? What is the difference between the mast cells and basophils? Mast cells live how long comparing to basophils? The enzyme of the Mast cells’ granules contain What is the function of mast cells? About how many percent of all WBCs are eosinophils? When is the number of eosinophils increased? ferritin (Fe+3) or as hemosiderin in white blood cells. Wilson’s disease massive increase of copper in the tissues in the brain, cornea, kidneys, and bones It is absorbed by the liver and combined with ceruloplasmin and returned to the plasma Basophils (in blood vessels) and Mast Cells (in tissues) Eosinophils Neutrophils Dendritic Cells Monocytes Natural Killer Cells Less than 1% They are the smallest of the granulocytes histamine, heparin, and eosinophilic chemotactic factor-A induce immediate hypersensitivity reactions vasodilation of the blood vessels white blood cells to migrate to the tissues faster, but also allows the plasma to leak out, which causes stuffiness and discomfort an anticoagulant IgE IgE binds to basophil cell membranes causing the granules to release when they contact an antigen A mast cell is similar to a basophil, but exists in the tissues The mast cells are larger and have more granules than basophils They live 9-18 months, whereas basophils only live a few days. acid phosphatase, alkaline phosphatase, and protease It functions the same as a basophil, by playing a role in hypersensitivity reactions by binding IgE 1-3% during an allergic reaction or in response to a 11 Immuno PPT Flashcards Unit 1 The eosinophil’s granules contain The eosinophil-specific granules contain What are the eosinophils capable of? How efficient the eosinophils are? The most important role of the eosinophils is Another name for Neutrophils are also called? Why are neutrophils sometime called “segs”? How many granules does a neutrophils contain? What color is primary granules contain? What defensive properties does primary granules contain? What does secondary granules have? What does tertiary granules contain? Acid hydrolases are called what, which are found in separate compartments? About what percentage of neutrophils are found in the blood vessels? Neutrophil circulate in the blood for how long? When WBC enter blood vessel tissue by a process called what? What the name of the receptor that make neutrophils become stick y like Velcro against the inside wall of the blood vessel? Diapedesis occurs when neutrophil sense a what? When neutrophils move toward or away from a chemical is called what? What the chemical messengers that cause cells to migrate in a particular direction? Some of the factor that effect chemotactic for neurtophils included? What the life span of a neutrophil once in the tissue? Named because they care covered with long membranous extensions that make them parasitic infection acid phosphatase several different proteins including peroxidase and neurotoxin They are capable of phagocytosis not efficient because they lack digestive enzymes neutralizing basophil and mast cell products and killing certain parasites Polymorphonuclear Neutrophils (PMN’s) Because of their segmented nucleus 3 types of granules -Primary granules -Secondary granules -Tertiary granules Blue Antibacterial proteins -collagenase, lactoferrin, lysozyme, NADPH, and protein found in cell membranes. Gelatinase and plasminogen activator Lysosomes About 50% About 6-10 hours Diapedesis Selectins Cytokine Chemotaxis Chemotaxins -complement components -proteins from coagulation -product of virus and bacteria -platlet activating factor -secretion from mask cells 5 days Dendritic cells 12 Immuno PPT Flashcards Unit 1 resemble nerve cell? What the main function of dentritic cells? Dendritic cells are classified according to their tissue location, true or false? Dendritic cells found on the skin and mucous membranes are called what? Dendritic cells found in the heart, lungs, liver, kidney, GI tracts are called what? In the secondary lymphoid tissue and thymus they are also called what? After dendritic cells capture an antigen by phagocytosis or endocytosis, where do they migrate? Dendritic cells are the most potent phagocytic cell in the tissue, true or false? What the name for monocytes when found in the tissue What he larges blood cells? What the shape of the monocyte? What the appearance of the monocytes? Phagocytose antigen and present it to helper T Lymphocytes True Langerhans cells Interstitial dendritic cells Interdigitating dentrici cells To the blood and lymph organs where they present antigen to T-lymphocytes to initiate the adaptive (humoral) immune response of making antibodies True macrophages Monocytes “horseshoe”shaped Grayish blue and has a ground glass appearance due to presence of fine dust-like granules Peroxidase, acid phosphatase, and arylsulfatase One type of monocyte contain similar property to neutrophils such as? Other type of monocyte granules contains what? Glucuronidase, lysozyme, and lipse, but no alkaline phosphatase. What percentage does monocyte make up of About 5-10% circulating WBCs? How long do monocyte stay in circulation? About 3 days After circulation for 3 days where they migrate To the tissue, where they are now called to? macrophages Once monocytes enter the tissue, it is now Macrophage, becomes larger and lose its called what? peroxidase Lung macrophages are called what? Alveolar macrophages In the liver they are called what? Kupffer cells In the brain they are called what? Microglial cells In the connective tissue they are called what? histiocytes When compare to neutrophil, are monocytes Slower, they are not as efficient as neutrophil in faster or slower? phagocytosis When compare to neutrophil do monocytes live Longer, can live for months instead of days longer or shorter? What role do monocyte perform? Help initiating and regulating the immune response, microbial killing, turmoricidal activity, intracellular parasite eradication, secretion of cell mediators, and antigen 13 Immuno PPT Flashcards Unit 1 Killing activity is enhanced when they become activated by what? What cell are the only lymphocytes that participate in cellular (innate) immunity? What can natural killer cells do? What the mechanism of natural killer cells? Does Natural killer cell participate in phagocytosis? Additional set of mechanism on certain cells are what? What exactly is Toll? Similarity of toll-like receptors are also found where? Higher concentration of toll-like receptors occurs on what WBCs? Each of toll-like receptors recognizes a different microbial product, true or false? How does toll-like receptors function? What kind of immunity does toll-like receptors enhance? How many steps occurs in phagocytosis? What are the 4 main steps? presentation. Contact with microorganism or cytokines which are release by T-lymphocytes Natural killer cells They are able to recognize self from non-self materials They will pop cell membrane of microorganis No Toll-like receptors It is a protein originally discovered in the frut fly Drosophila, where it plays an important role in antifungal immunity in adult Similar molecules are found on human leukocytes and some non-leukocyte cell types Monocytes, macrophages, and neutrophils True Once a receptor binds to its particular substance, or ligand, phagocytosis may be stimulated, or the cell produces cytokins that enhance inflammation and eventual destruction of the microorganism. Innate immunity 4 main steps 1. Physical contact between the white cell and the foreign particle 2. Formation of a phagosome 3. Fusion with cytoplasmic granules to form a phagolysosome 4. Digestion and release of debris to the outside Chemotaxis from chemicals such as bacterial factors, complement components, or CRP Enhanced by opsonins Neutrophils and macrophages migrate by what mechanism? Receptors on the phagocyte come in contact with foreign particle surface and activates what? What are opsonins? They are serum proteins that attach to the foreign substance, such as antibodies, CRP, and complement components. How does phagocytosis work? Phagocyte has receptors that attach to the opsonin, and grab it like a handle so it can ingest the foreign object or bacterium 14 Immuno PPT Flashcards Unit 1 How does opsonin help in phagocytosis? What is opsonization? Opsonization are perform by opsonin serum protein, true or false? What the process of phagocytosis? An increase in oxygen consumption in phagocytosis is termed Once the particle is inside the phagocyte the vacuole is called what? When the cytoplasmic granule fuse to the phagosome, and the entire complex is now called what? The granules release their contents, and digestion occurs, true or false? Any undigested material is excreted by what? The duration of the whole process of phagocytosis take how long? During the respiratory burst or oxidative burst, the bacterial activates what? Superoxide is highly toxic but can be rapidly converted to more lethal products, true or false? By adding hydrogen ions, the enzyme superoxide disumatase converts superoxide to what? Hypochlorite ions help potentiated the effect, true or false? How is this accomplished? New evidence indicates that an enzyme known as what, will depolarize the bacterial cell membrane, allowing hydrogen potassium ions to enter the vacuole? When hydrogen combines with the superoxide, what happen to the pH? Increase or decrease? What does increase in pH activates? The dysfunction of the NADPH oxidase system causes what disease? What the out come of chronic granulomatous Opsonin may act by neutralizing the surface charge on the foreign particle, making it easier for the cells to approach one another Is the process whereby a substance binds to the foreign object to enhance phagocytosis True Once attachment occurs, the phagocytes’ cytoplasm forms pseudopods and engulfs the particle. This cause an increase in oxygen consumption. Respiratory burst or oxidative burst Phagosome Phagolysosomes True Exocytosis About 20 seconds The cell membrane of the phagocytic cell, and a radical known superoxide is formed True To hydrogen peroxide or the hydroxyl racial OH True Action of the enzyme myeloperoxidase in the presence of chloride ions. Hypochlorite ions are powerful oxidizing agents. Enzyme from Electron transport system called NAPDH Increase pH Activates protease (protein digesting enzymes) which contribute to microbe killing Chronic granulomatous disease Patients suffer from recurring, severe bacterial 15 Immuno PPT Flashcards Unit 1 disease? What is termed inflammation? What immunity are involved? What are the four clinical symptoms of inflammations? What are some examples of major events that associated with process of inflammation? When inflammation occurs what chemical mediator are release? What the purpose of histamine? Vasodilation allows what to leaked into the tissues? When vasodilation causes plasma to leaked in to the tissue causes what to happen? What soluble mediators initiate and control the response? Amplification occurs through what formation? As the endothelial cells contract, which WBCs move out of circulation and into the tissue? Neutrophils are attracted by what substance? Neutrophils are mobilized within how many minutes after the injury? How long does neutrophil emigration last? Migratin of macrophates from surrounding tissue and from blood monocytes occurs when? Macrophages attempt to clear the area through what process? When the inflammation process becomes proglonged it is said to be what? What may contribute to the damage? Failure to remove microorganism or injured infections Overall reaction of the body to injury or invasion by an infectious agent. Both cellular and humoral mechanism are involved • Redness (rubor) • Swelling (tumor) • Heat (calor) • Pain (dolor) • Increased blood supply to the infected area • Increased capillary permeability • Migration of white blood cells, mainly neutrophils to the injured area • Migration of macrophages to the injured area Histamine Released from injured mast cells which causes dilation of blood vessels and bring additional blood flow to the affected area, resulting in redness and heat Plasma Produce swelling, and pain from the fluid pressing on nerves Acute-phaase reactants Formation of clots by the coagulation system and then the triggering of the fibrinolytic system Neutrophils Chemotaxis 30-60 minutes 24-48 hours Several hours later and peaked at 16 to 48 hours Phagocytosis Chronic, and tissue damage and loss of function may result Specific immunity with infiltration of lymphocytes Continued tissue damage 16 Immuno PPT Flashcards Unit 1 tissue may results in what? What is the most widely monitored of the acute phase reactants and is the best indicator of acute inflammation? What are of primary importance in the lymphoid system’s immune response? Lymphocytes represent between what percent of the circulating white blood cell? The size of small lymphocyte is typically between what in diameter? Does a lymphocyte have a nucleus? What color does the nucleus stain? What does the lympocyte’s cytoplasm container? What is lymphocytes rise from? Where is hematopoietic stem cell further differentiate in? Where is the primary lymphoid organs in human located? The lymphocytes that go from the bone marrow to the thymus glad differentiate into what? Those that stay in the bone marrow to differentiate are called what? The secondary organs in the lymphoid system includes what? The main contanct with foreign antigens take place in secondary or primary organ? The spleen is part of what lymphoid system? The spleen serve what purpose? What does the lymph nodes do? Mucosal surface are equip with what? The circulation of lymphatic fluid are controlled by what? T lymphocytes are also known as what type of cell that serve a regulatory role? What the main purpose of B lymphocytes Which lymphocytes recirculate continuously from the bloodstream to the secondary lymphoid organs and back, to increase contact with foreign antigens? A third type of lymphocyte, with large granules, plays a role in both the innate and adaptive immune response? C-reactive protein (CRP) Lymphocytes About 20-40% between 7 and 10 μm Yes Deep blue Contains a few organelles with no specific granules, and stains a lighter blue Hematopoietic stem cell in the bone marrow Primary lymphoid organs Bone marrow and the thymus T-cells (T for thymus) B-cell (bone marrow) Spleen, lymph nodes, appendix,tonsils, and other mucosal-associated lymphoid tissue Secondary organs Secondary organ Serves as a filtering mechanism for antigens in the bloodstream Help filter fluid from the tissue Backed with lymphoid tissue as an additional means of contacting foreign antigens as they enter the body cytokines Effector cells Produce antibodies Both T and B lymphocytes NK cells (Natural Killer cell) 17 Immuno PPT Flashcards Unit 1 T,B, and NK cell arise from what common precursor? In the peripheral blood, what percent of all lymphocyte make up B cells? In the peripheral blood, what percent of all lymphocyte make up T cells? In the peripheral blood, what percent of all lymphocyte make up NK cells? What are the two primary lymphoid organs? All lymphocytes arise from what stem cell? Where does pluripotential hematopoietic stem cells found in? The bone marrow assumes this role when the infant is born, true or false? What organ can be considered the largest tissue of the body? Where are bone marrow found? Which bone marrow is the source of the hematopoietic stem cells? What can red bone marrow give rise to? The bone marrow functions as what? T, B, and NK cells arise from what precursor? Lymphocyte leave what organ and migrate to the primary lymphoid organs where they differentiate further? Some of these cells will go to the thymus and develop into what cell? While the other remain in the bone marrow and mature into what? T cells develop their identity characteristic in what organ? Where is the thymus organ located? The thymus gradually atrophies at what age? Most of the virgin T cells are produce during when? The thymus are capable of producing new T cells until what age? Progenitors of T cells appear in the fetus as early as? By the time the infant is born the differentiation of lymphocytes take place during when? There are two different layer of the thymus Common lymphoid precursor (CLP) About 10-20% About 61-89% Up to 22% Bone marrow and Thymus Pluripotential hematopoietic stem cell Yolk sac of developing embryo and are later found in the fetal liver True Bone marrow In the epiphyses of long bones and is also found in flat bones of the body, especially the iliac crest, the vertebral bodies, and the sternum Red bone marrow Erythrocytes, granulocytes, monocytes, platelets, and lymphocytes The center for antigen-independent lymphopoiesis Common lymphoid precursor (CLP) Red bone marrow T cells B cells Thymus Sits on top of the heart After puberty First three years of life Fifth or sixth decade of life Eight weeks in utero Early in fetal development Cortex (outer edge) 18 Immuno PPT Flashcards Unit 1 called? Mature T lymphocytes are released from what area of the thymus? Once differentiation occurs, mature T lymphocytes are released from what organ? Once differentiation occurs, mature B lymphocytes are released from what organ? After differentiation is complete where do lymphocytes migrate to? Secondary lymphoid organs consist of what tissue? The lymphocytes travel through the tissue and return to the bloodstream by what body part? Each lymphocytes spend most of its life in what kind of tissue? Lymphocytes go from one secondary organ to another via what route? Recirculation increase the likelihood of a lymphocyte to come in contact with what? Lymphopoiesis occurs in what tissue? The reproduction of lymphocytes is termed what? Most naïve or resting lymphocytes die with in how many days? Within a few days most lymphocyte will die if they are not activated by the presence of what? It is this second process that gives rise to the long-lived? What is the largest secondary lymphoid organ? Where is the spleen located? What the purpose of the spleen? The spllen has two type of tissue known as what? What percentage does the red pulp make up? What is the function of red pulp? Blood flow into the red pulp via what? Blood flow from the arterioles into the red pulp but exits through what vein? What percentage does the white pulp make up? The sheath within the white pulp contain what cells? Medulla (inner area) Medulla (inner area) Thymus Bone marrow Secondary lymphoid organs and become part of the the recirculating pool Spleen,lymph nodes, tonsils, appendix, peyer’s patches in the intestines, and other mucosalassociated lymphoid tissue Thoracic duct Solid tissue Circulation Specific antigen Secondary tissue Lymphopoiesis Within a few days Foreign antigen Memory cells Spleen Upper left quadrant of the abdomen just below the diaphragm and surround by a connective tissue capsule Act like a sponge to help remove old and damaged cells and foreign antigens from the blood Red pulp and white pulp More than one-half of the spleen Function to destroy old red blood cells Arterioles Splenic vein About 20% of the spleen T cells 19 Immuno PPT Flashcards Unit 1 Attached to this sheath are primary follicles, which also contain what cell that are not yet stimulated by antigen? Surrouding the PALS (periarteriolar lymphoid sheath) containing what cells? Lymphocytes enter and leave the spleen by mean of many what? Each day blood volume passes through the spleen approximately how many times? At the same time allow what WBCs to constantly survey for infectious agents and other foreign matter? The white pulp composes of approximately what percentage of the total weight of the spleen? White pulp contains what kind of tissue? Where are lymph nodes located? What is the purpose of lymph nodes? Lymph fluid arises from what? Some of the interstitial fluid returns to the bloodstream via what? Lymph nodes are especially numerous near what body part? Filtration is a main function of what tissue? The lymph nodes contains what, which are lined with macrophages? The lymph node is organized into how many parts? The lymph fluid flows slowly through spaces called what? Sinuses are line with what? Macrophages allow what process to take place? Foreign antigens enter the lymph nodes through what vessels? Numerous lymphocytes also enter the nodes from what? The outermost layer of the lymph node is called what ? The cortex of the lymph nodes contains what? Specialized cells called what are also located in the primary follicles? B cells Dendritic cells that trap antigen Capillary branches that connect to the arterioles Approximately 4 times Lymphocytes and macrophages 20% Lymphoid tissue Along lymphatic ducts Serve as central collecting points for lymph fluid from adjacent tissue Passage of fluids and low-molecular-weight solutes out of the blood vessel walls and into the interstitial spaces between cells Venules Joints and where the arm and legs join the body Lymph nodes Sinuses Outer cortex Paracortex Medulla Sinuses Macrophages Phagocytosis Afferent lymphatic vessel Bloodstream by mean of specialized venules called high endothelial venules The cortex Macrophages and aggregations of B cells in primary follicles Follicular dendritic cells 20 Immuno PPT Flashcards Unit 1 Follicular dendritic cells are found only in what? Follicular dendritic cells exhibit large number of what? The secondary follicles consist of what? The interior of a secondary follicle is known as what? What so important about germinal center? What does plasma cell secrete? B-cell memory is a primary function of? Where does T lymphocytes mainly localized? Paracortex is located where? The medulla is more or less dense? Medulla contains what cells? Particulate antigens are removed as the fluid travel across what? The transit time through a lymph node is about how many hours? Fluid and lymphocytes exit by way of what? Lymph nodes eventually connect with the thoracic duct and the venous system to recirculate what? Additional areas of lymphoid tissues includes? MALT is found where? What does Peyer’s patches represent? Another area of lymphoid tissue found in the mucus membrane lining of the oral and pharyngeal cavities Additional location of lymphoid tissue is the what? All of these secondary organ function as what? The cutaneous-associated lymphoid tissue with the epidermis contains what? Within each of these secondary organs, which cells are segregated and perform specialized functions? B cells differentiate into what? Plasma cell and memory cells are responsible Lymphoid follicles and have long cytoplasmic processes that radiate out like tenticles Receptors for antibody and complement and help to capture antigen to present it to T cells and B cells Antigen-stimulated proliferating B cells Germinal center It is where blast transformation of B cells take place Secrete antibody and memory cells Lymph nodes Paracortex Region between the follicles and the medulla Less dense T cells in addition to B cells, macrophages, and numerous plasma cells Lymph node from cortex to medulla 18 hours Efferent lymph vessels Between lymph nodes and blood MALT, tonsils, appendix, and cutaneousassociated lymphoid tissue In the gastrointestinal, respirator, and urogenital tracts Represent a specialized type of MALT and are located at the lower ileum of the intestinal tract tonsils Appendix Potential sites for contact with foreign antigen, and they increase the probability of an immune response. Intraepidermal lymphocytes, where most of these are T cells T and B cells Plasma cells and memory cells Humoral immunity or antibody formation 21 Immuno PPT Flashcards Unit 1 for what immunity? T cells play a role in what immunity? B cells are derived from what precursor? Common lymphoid precursor differentiate into what? Early lymphocyte progenitors can becomes what? What are some example of differentiation of B cell? The earliest B-cell precursor can be recognized by the presence of a surface molecule called? What so important about antigen-independent phase? How does influence of growth factors and cytokines effect the differentiation of B cells? After the rearrangement of genes occurs what is the outcome? When B lymphocytes produce two identical light chains and two identical heavy chains, what is this process called? What are some example of markers that exist on surface of pro-B cells? In order for pro-B cells to differentiate into preB cell successfully what must occur? What cell interact with pro-B cells to secrete cytokines, hormones, chemokines, and adhesion molecules? What does the pre-B stage begins? After pre-B cells is complete which marker surface marker does it lose? Where does Mu chains accumulate? Which combination of chain forms the pre-B cell receptors? The pre-B cell receptor adheres to what part of Cell-mediated immunity and produce sensitized lymphocytes that secrete cytokines Common lymphoid precursor (CLP) B cell progenitor cell T-cell, B-cell NK cells, or dendritic cells • • • • • • • Pro- B cells Pre-B cells Immature B cells Mature B cells Activated B cells Plasma cells Memory cells CD45R Process that prepares them for their role in antibody production and restricts the types of antigen to which the cell can respond. This causes rearrangement of genes to occur and codes for the heavy and light chains of an antibody molecule. B lymphocyte programmed to produce a unique antibody molecule, consisting of two identical light chains and two identical heavy chains. Pro-B cell CD19, CD45R, CD43, CD24, and c-Kit Successful rearrangement of heavy-chains genes. Stromal cells When synthesis of the heavy chain part of the antibody molecule occurs CD43 marker as well as c-Kit and TdT In the cytoplasm Combination of two heavy chains and two surrogate light chains plus two very short (Ig-α and Ig-β) Bone marrow stromal cell membranes and 22 Immuno PPT Flashcards Unit 1 the body? Which cell only express heavy chains in association with surrogate light chain? The next stage after pre-B cells is known as what? Immature B cells have what molecules on the cell surface? Its specificity is determine by what? What other surface protein appears on the immature B cell? The receptor that help breakdown product of the complement component C3, and C3d? Antigen coated with complement fragments during the immune response help trigger what? CD40 and MHC class II are important for which interaction? Many B cells are deleted form the marrow by the process of programmed cell death, termed? Which organs doe immature B cells leave and proceed to? In the spleen, what does immature B cells develop into? Mature B –cells in the spleen is also called what? B cells remain in the spleen to do what? Other immature B cells differentiate into what and where are they found? Besides IgM antibody, which class of antibody are exhibit? How does IgD affect the life span of mature B cells in the periphery Unless contact with antigen occurs, the life span of a mature B cell is typically how many days? What occurs when B cell is stimulated by antigen? The transformation process is known as what? What the half-life of B cells? Where does antigen-dependent activation of B cells take place in? Activated B cells exhibit identify markers including? What is Interleukin- 2? transmits a signal to prevent rearrangement of any heavy-chains genes Pre-B cells Immature B cell IgM molecules Variable regions, which occur on both the light and heavy chains of the antibody molecules CD21, CD40, and MHC class II molecules CD21 Enhances the likelihood of contact between B cells and antigen B cells with T cells Apoptosis Leave bone marrow and proceed to seed the spleen and other secondary lymphoid organs Mature B- cells Marginal zone B cells Respond quickly to any bloodborne pathogens they may come in contact with Become follicular B cells, which are found in the lymph nodes and other secondary organs All mature B cells exhibit IgD on the surface Prolong it Few days It undergoes transformation to a blast stage, which eventually forms memory cells and antibody-secreting plasma cells Antigen-dependent phase of B cell development More than 6 weeks The primary follicles of peripheral lymphoid tissue CD25, which is found on both activated T and B cells and acts as a receptor for Interleukin 2. A growth factor produced by T cells 23 Immuno PPT Flashcards Unit 1 When B cells are activated in this manner, they transform into what? What are the size of plasma cells? Does a plasma cell have abundant cytoplasmic immunoglobulin or abundant surface immunoglobulin Where are plasma cells located? Do plasma cells divide? Plasma cells can differentiate into what type of cells? Where are memory B cells located? How long due memory cells remain activated? What percentage of circulating lymphocytes are T cells? What are lymphocyte precursors called? Where do thymocytes enter and migrate? What is T cell differentiation driven by? What are the early surface markers of T cells? Are distinct surface markers created during specific stages of development How long does T cell differentiation take? What are the thymic stromal cells? What percentage of the cortical cells die intrathymically before maturing completely? Early thymocytes lack which CD markers? Double negative thymocytes proliferate under the influence of which IL? How many chains does CD3 have? The alpha and beta chains have variable regions. What does that mean? When a functional beta chain is seen on the cell surface, what happens? Signaling by the beta chain triggers what response in the thymocyte? Do thymocytesexpress gamma and delta chains? Thymocytes with gamma and delta chains are + or – for CD4 and CD8? Where are negative CD4 and negative CD8 cells located? Cells that are negative for CD4 and negative for CD8 may behave like what other type of cell? When cells express both CD4 and CD8 antigens, what are the cells called? Blast cells that will give rise to both plasma cells and so-called memory cells 10-20um Abundant cytoplasmic immunoglobulin In the germinal centers of peripheral lymphoid organs No Memory B cells Germinal centers Months or years 60-80% Thymocytes They enter the thymus and migrate to the cortex Chemokines CD44 and CD25 Yes 3 weeks Epithelial cells, macrophages, fibroblasts and dendritic cells 97% CD4 and CD8 IL-7 8 It means that those regions recognize specific antigens A signal is sent to suppress further beta chain gene rearrangements Allows thymocyte to become CD4 and CD8 positive Yes Negative Intestinal epithelium and pulmonary epithelium Natural Killer cell Double positive cells 24 Immuno PPT Flashcards Unit 1 Thymocytes that are unable to recognize self antigens die where? Approximately how many double positive thymocytes survive T cell differentiation? Thymocytes that express both CD4 and CD8 antigens are called what? True/False: Survivors of selection exhibit only 1 type of marker, either CD4 or CD8. CD4+ cells are also known by what name? CD8+ cells are also known by what name? What MHC class do CD8+ cells recognize? What lymphoid organ are mature T cells released from? In peripheral organs, how long can resting T cells live? What do TH1 cells produce? Which interleukins do the Th2 cells produce? What is the main role of the TH 2 cell? Which antigens do T-regs possess? What is the main function of T regs? How do T regs suppress the immune response? What are the 3 types of T cells? What CD markers do NK cells have? What CD markers do helper T cells have? Single positive T cells spend how many days in the thymic medulla? What do T regulatory cells prevent? After leaving the thymus, where do T cells migrate? Where must antigens be transported for activation? T lymphocytes transform into what cells when antigen recognition occurs? Activated T lymphocytes express receptors for what IL? What do T lymphoblasts differentiate into? Do memory T cells express a broader or limited array of cytokines? All activities of T cells make up what? Do natural killer cells express the markers of T In the thymus 1-3% Double positive True T-helper or inducer cells T-cytotoxic cells MHC class I Thymus Several years IFN-B and INF-Y IL-4, IL05, IL-10, and IL-13 To help B cells produce antibodies CD4 and CD25 To suppress the immune response to selfantigens They produce interleukins such as IL-10 and transforming growth factor B Helper T cells, Natural killer cells, and suppressor T cells CD8 CD4 12 days They prevent autoimmune reactions with any surviving T cells that can react with self antigens Secondary lymphoid organ T cell zones of the secondary lymphoid tissue Large activated cells IL-2 Functionally active small lymphocytes Broader Cell mediated immunity No/Neither 25 Immuno PPT Flashcards Unit 1 or B cells? What percentage of the circulating lymphoid pool do natural killer cells make up? What is a unique ability of the natural killer cell? True/False: Natural killer cells lack specificity in their response? What cell line do NK cells arise from? NK cells in the bone marrow respond to which IL to become NK cells? NK cells present in the thymus become what cell? What are the 2 CD markers present on NK cells? NK cells high in CD56 and with little CD16 have what function? NK cells high in CD16 but low in CD56 provide what function? Name the 3 cytokines that stimulate NK cells. Healthy self cells have which MHC class proteins on their membrane? What substances do NK cells release to kill cells? What is the function of granzymes? What laboratory method is used to identify T and B lymphocytes? What are the 5 CD markers recognized on T cells? What are the 3 CD markers recognized on B cells? What is an antigen? What 3 factors cause a lack of immune response? Name the 5 factors that influence the nature of the immune response. What 3 populations have decreased immune responses? True/False: The larger the dose of an immunogen one is exposed = greater the immune response What happens if a person receives large doses of an immunogen? Does the amount of immunogen needed to 5-10% To kill target cells without prior exposure to them True Common lymphocyte precursor IL-15 T cells CD 16 and CD 56 Produce cytokines to support antibody production Produce cytokines to support cytotoxic activity Il-12, interferon gamma, and interferon beta MHC I Perforins and granzymes To lyse the cell Flow cytometry CD2, 3, 4, 7, and 8 CD19, 20, and 22 A substance that reacts with an antibody or sensitized T cell, but may not invoke an immune response Nature of the immunogen, genetic coding of MHC molecules, immunogen processing and presentation Age, overall health, dose, route of transmission, and genetic capacity Older people, newborns, and people in poor health True T and B cell tolerance Yes 26 Immuno PPT Flashcards Unit 1 generate an immune response differ with route of inoculation? Name the 4 routes for an immunogen Does genetic predisposition play a role in individual’s response to a particular immunogen? Name the 4 characteristics that influence the ability of an immunogen to stimulate a host What is the minimum molecular weight of an immunogen to be recognized by the immune system? The _______ the molecular weight, the more potent the molecule is an immunogen What are the 2 best immunogens? What are the proteins composed of? If a string of amino acids are in a helix, is that primary, secondary, or tertiary structure? What do proteins contain that stimulate T cells? Are synthetic polymers immunogenic? Since synthetic polymers lack immunogenicity, what are they used to make? Why are carbohydrates less immunogenic than proteins? As immunogens, carbohydrates occur most often in what form? Are the A and B blood antigens glycolipids or glycoproteins? Are the Rh antigens glycolipids or glycoproteins? Substances recognized by the immune system as non-self are immunogenic or nonimmunogenic? What happens to lymphocytes that are capable of reacting with self antigens? What is a better immunogen, a plant or animal protein? True/False: Pure nucleic acids and lipids are immunogenic by themselves Is foreignness a characteristic that all immunogens share? What is antigen processing? For a substance to elicit an immune response, IV, intradermal, subcutaneous, and oral Yes Macromolecular size, chemical composition and molecular complexity, foreignness, ability to be processed and presented with MHC molecules At least 10,000 daltons Greater Proteins and polysaccharides Amino acids Secondary Epitopes No Heart valves, elbow replacements and other medical appliances The units of sugars are more limited than the number of amino acids in proteins Glycolipids and glycoproteins Glycolipids Glycoproteins Immunogenic They are eliminated Plant protein False Yes Enzymatic digestion to create small peptides that are complexed to MHC molecules to present to responsive lymphocytes Yes 27 Immuno PPT Flashcards Unit 1 does it have to undergo antigen processing? True/False: If an antigen cannot be joined with an MHC molecule, it would be a poor immunogen What is the determinant site? What cells recognize epitopes? True/False: Large molecules have few epitopes Are epitopes sequential in nature? What is the molecular weight of an immunogen? What portion of the immunogen is recognized in the immune response? What cells recognize epitopes? What are the shapes of epitopes? The folding of 1 chain or multiple chains bringing certain AAs so they ca be recognize together is which epitope? True/False: Epitopes recognized by B cells may differ from those recognized by T cells Surface antibodies on B cells react with what epitopes? What will trigger B cell activation? If an immunogen is a protein, B cells will recognize which structure? In polysaccharides, do the branch points contribute to recognition? Are T cells able to recognize an epitope without MHC proteins on the surface? What must an antigen presenting call do to process an immunogen? Are T cell epitopes linear or conformational? If some substances are too small for recognition, what can they do? What are haptens? Can a hapten react with antibody when the hapten is not complexed to a carrier molecule? What reaction can occur when haptens crosslink with more than 1 antibody molecule? What hapten does poison ivy contain? What does poison ivy cause on the skin? True/False: Therapeutic drugs and hormones True Part of the immunogen that is actually recognized in the immune response T or B lymphocytes False Yes At least 10,000 Daltons Determinate site or epitope B or T cells Linear and conformational Conformational True Both linear and conformational Anything that will cross-link to immunoglobulin The primary, secondary, tertiary, or quaternary structure Yes No It must degrade the immunogen Linear Bind to larger molecules to stimulate a response Nonimmunogenic materials that, when combined with a carrier, create new antigenic determinants Yes, when antibody production is initiated Precipitation or agglutination reactions Catechol Contact dermatitis True 28 Immuno PPT Flashcards Unit 1 can function as haptens How are antigens categorized? What are autoantigens? Do autoantigens evoke immune responses under normal circumstances? What are alloantigens? What are heteroantigens? What are heterophile antigens? What is an adjuvant? How does an adjuvant function? What is the only adjuvant approved for clinical use in the US? True/False: The hepatitis B vaccine uses an adjuvant What antigens determine organ histocompatibility? Where are MHC molecules found? What is the main function of the MHC molecules? Why are MHC molecules clinically relevant? Genes that control expression of molecules are known as? True/False: The MHC system is polymorphic On what chromosome is the coding for the MHC molecules located? How many classes of the MHC molecule are there? How many locations are class I molecules coded for? Where are class II genes situated? What do class III genes code for? What are class I and II gene products involved in? True/False: Class III proteins are secreted proteins expressed on cell surfaces How many copies of chromosome 6 does a person inherit? Based on relationship to host Antigens that belong to the host No Antigens from other members of the host’s species Antigens from other species, such as other animals, plants, or microorganisms Heteroantigens that exist in unrelated plants or animals that are either identical to or closely related in structure so that antibody will crossreact with antigen of the other A substance administered with an immunogen that increases the immune response It acts by producing a local inflammatory response that attracts a large number of immune system cells to the injection site Aluminum salts True MCH molecules In all nucleated cells To bring antigen to the cell surface for recognition by T cells They are involved in transfusion reactions, graft rejection, and autoimmune diseases Major histocompatibility complex True Chromosome 6 3 3 In the D region Complement proteins and cytokines Antigen recognition False 2 copies 29 Immuno PPT Flashcards Unit 1 True/False: MHC genes are codominant What is a haplotype? What are in each haplotype? Polymorphism of MHC has implications in what? True/False: Class I MHC molecules are expressed on all nucleated cells What cells contain the most class I MHC molecules? In what type of organ transplants is HLA testing not completed? True/False: HLA-C antigens have the lowest expression of HLA antigens What cells have class II MHC molecules? What are the 3 major class II molecules? Which class II molecule is expressed at the highest level? What are the 3 other class II genes? Products of the nonclassical class II genes do what? What is the main role of class I and class II MHC molecules? True/False: T cells can respond to antigens without being combined with MHC molecules What molecules do class I molecules present? True/False: Class I molecules act as watchdogs for viral antigens What cells do class II molecules present? When do class II molecules stimulate CD4 cells? Where are class I and class II molecules synthesized? Where do class I molecules bind peptides? Peptides that associate with class I molecules are how many amino acids in length? What are TAP 1 and TAP 2 proteins responsible for? What chain must bind the peptide, MHC-1 peptide complex to transport to the cell surface? How do class I molecules determine which antigens an individual will respond? True MHC genes that are closely linked and inherited together as a package A, B, C, DR, DP, DQ Organ donation and paternity testing True Lymphocytes Liver transplants True B lymphocytes, monocytes, macrophages, and dendritic cells DP, DQ, and DR DR DM, DN, and DO Play a regulatory role in antigen processing Bind peptides within cells and transport them to the plasma membrane, where T cells can recognize them in the phenomenon known as antigen processing False Peptides True They present antigens to CD 4 cells In bacterial infections Rough endoplasmic reticulum In the rough endoplasmic reticulum 8-10 amino acids Responsible for the ATP- dependent transport from the cytoplasm to the lumen of the endoplasmic reticulum Alpha chain Binding affinities 30 Immuno PPT Flashcards Unit 1 Class I molecules complexed to antigens allow CD 8 positive T cells to continuously do what? Before class II molecules can bind peptides, where must they be transported? Which cells are the most potent activators of T cells? What helps to unfold molecules and uncover functional sites? What enzyme degrades an invariant chain? When the invariant chain is degraded, what fragment is left? What molecule helps to remove the CLIP fragment? Do class I or class II molecules have a closed end? Does hydrogen bonding take place along the length of the peptide in class II molecules? Can class II proteins accommodate amino acid side chains? Once class II protein – peptide complex is stabilized where is it transported? What makes up a trimolecular complex? What results when binding occurs with a T-cell receptor on a CD4-positive T cell and then T helper cell recruits and triggers a B-cell response? Why is testing for MHC antigens typically done? Which test method for MHC antigens is more accurate? What is the major role of MHC molecules? What role do MHC antigens play? True or False: MHC molecules typically have a broad binding capacity and small biochemical differences in these proteins are responsible for differences seen in the ability to react to a specific antigen. True or False: MHC molecules to a particular vaccine such as hepatitis B do not have the genetic capacity to respond. What is an example of the presence of a particular MHC protein conferring additional Check cell surfaces for the presence of non-self antigens To the endosomal compartment Dendritic cells Antigen processing Protease Class II invariant chain peptide HLA-DM Class I molecules Yes Yes To the cell surface Class II molecules are responsible for forming the trimolecular complex that occurs between antigen, the class II molecule, and an appropriate T-cell receptor Antibody formation Both class I and class II molecules can induce a response that leads to graft rejection Molecular method They determine the types of peptides to which an individual can mount an immune response Development of autoimmune disease True True HLA B8 and the increased resistance to HIV infection 31 Immuno PPT Flashcards Unit 1 protection? What is made when B cells are stimulated by antigen? What are antibodies also known as? What does “globin” refer to? Where are immunoglobulins found? Immunoglobulins are composed of about ____ polypeptide and about ____ carbohydrate. What are the 5 classes of immunoglobulins? Immunoglobulins are considered to be the humoral branch of the ____ _____. What is the essential role of immunoglobulins? Are opsonization and complement activation roles of immunoglobulins? (T or F) All immunoglobulin molecules share many common features. What kind of unit are all immunoglobulin molecules made up of? What does the basic four-chain polypeptide unit consist of? How are the H chains and L chains held together? When subjected to electrophoresis at 8.6, immunoglobulins appear primarily in the ___ band. When was the structure of antibodies first discovered? What was used to cleave IgG into 3 pieces of about equal size, each having a sedimentation coefficient of 3.5 Svedberg units (S) and representing a molecular weight of approximately 45,000 to 50,000 Daltons (d)? What separated the material into two types of fragments, on which spontaneously crystallized a 4°C? What fragment had no antigen-binding ability and is known to represent the carboxy-terminal halves of two H chains that are held together by S-S bonding? What do antibodies consist of? What is important in effector functions of immunoglobulin molecules, which include opsonization and complement fixation? Antibodies Immunoglobulins Globular shape of protein Serum portion of blood 85%; 10% IgG, IgM, IgA, IgD, IgE Immune response Antigen recognition and biological activities related to immune response Yes True Four-chain polypeptide unit 2 heavy (H) chains and 2 light (L) chains Non-covalent forces and disulfide interchain bridges Gamma 1960’s Proteolytic enzyme papain Carboxymethyl cellulose ion exchange chromatography FC fragment (“fragment crystallizable) Light and heavy chains that form an FC fragment, Fab fragment, and a hyervariable region FC fragment 32 Immuno PPT Flashcards Unit 1 What are the remaining 2 identical fragments called? Because precipitation would not occur if Fab fragments were allowed to react with antigen, what was gu100,essed that each fragment represented? What does each Fab fragment consist of? How is each Fab fragment held together? What was found to cleave IgG at the carboxyterminal side of the interchain disulfide bonds, yielding one single fragment with molecular weight of 100,000 d and all the antigen-binding ability, known as F(ab)2? What additional fragment was similar to FC except that it disintegrated into several smaller pieces? What is found in the urine of patients with multiple myeloma? What type of chains were being secreted by malignant cells in patients with multiple myeloma? Who discovered Bence Jones proteins in 1845? When heated to 60°C, Bence Jones proteins ____ from urine, but on further heating to 80°C, they ____. What were the two main types of L chains in Bence Jones proteins? How much amino acid is contained in each L chain? What was the region called from positions number 111 and one where each type had essentially the same sequence? What was the amino-terminal end called? What is the difference between the κ and λ chains? (T or F) Both κ and λ L chains are found in all 5 classes of immunoglobulins, but only one type is present in a given molecule. What demonstrated the presence of domains similar to those in the L chains- that is, variable and constant regions? What is the first approximately 110 amino acids at the amino-terminal end? What are the remaining amino acids typically divided up into? Constant regions of the _____ are unique to Fab fragments (fragment antigen-binding) One antigen-binding site and that 2 such fragments were present in an intact antibody molecule One L chain and one-half of a H chain Disulfide bonding Proteolytic enzyme pepsin FC’ Bence Jones porteins L chains Dr. Henry Bence Jones precipitated; redissolved Kappa (κ) and lambda (λ) Between 200-220 amino acids Constant region Variable region Amino acid substitutions at a few locations along the chain True H chain sequencing Variable domain 3 or more constant regions with similar sequences (CH1. CH2, CH3) H chain 33 Immuno PPT Flashcards Unit 1 each class and give each immunoglobulin type its name. What chain does IgG have? What chain does IgM have? What chain does IgA have? What chain does IgD have? What chain does IgE have? What is an unique amino acid sequence that is common to all immunoglobulin molecules of a given class in a given species? What are minor variations of amino acid sequences that are present in some individuals but not others? What do the variable portions of each chain that are unique to a specific antibody molecule constitute? What is essential to the formation of the antigen-binding site? What is the segment of H chain located between the CH1 and CH2 regions? What does the hinge region have a high content of? What does the high proline content allow for? What does the ability to bend in the hinge region allow for? What is an example of an effector function? What chains have a hinge region? What chains do not have a hinge region? (T or F) The CH2 domains of the latter two chains are paired in such a way as to confer flexibility to the Fab arms. What do all types of immunoglobulins contain? Where is the carbohydrate portion located? What are the functions of the carbohydrate portion? (T or F) The basic four-chain structure of all immunoglobulin molecules does not exist as a straight “Y” shape. Is the basic four-chain structure of the Ig folded into compact globular subunits? What is the basic four-chain structure of Ig based on? What type of bonds stabilize the globular regions? γH chain μ chain α chain δ chain ε chain Isotype Allotypes Idiotype The aminoterminal ends of both L and H chains contain these variable regions Hinge region Proline and hydrophobic residues Flexibility Two antigen-binding sites to operate independently Initiation of the complement cascade Gamma, delta, alpha Mu and epsilon True Four polypeptide chains and a carbohydrate portion Between the CH2 domains of the two H chains Increasing the solubility of Ig, providing protection against degradation, and enhancing functional activity of the FC domains. True Yes The formation of balloon-shaped loops at each of the domains Intrachain disulfide bonds 34 Immuno PPT Flashcards Unit 1 Within each of the regions or domains, what is formed when the polypeptide chain is folded back and forth on itself? What cylindrical structure is produced when the folded domains of the H chains line up with those of the L chains? What is captured within the barrel by binding to a small number of amino acids at strategic locations on each chain (hypervariable regions)? What is the predominant immunoglobulin in humans? What is the percentage of total IgG in humans? (T or F) IgG has the longest half-life of any Ig class? How long is the IgG half-life? What are the four major subclasses of IgG? Beta-pleated sheet Immunoglobulin fold or barrel Antigen IgG 75-80% True 23-25 days IgG1 (67%), IgG2 (22%), IgG3 (7%), IgG4 (40%) How do the four major subclasses of IgG differ? In the number and position of the disulfide bridges between the chains Which type of immunoglobulin has the largest IgG3 hinge region and the largest number of interchain disulfide bonds, and is the most efficient at binding complement? Which type of immunoglobulins have shorter IgG2 and IgG4 hinge segments and tend to make poor mediators of complement activation? What are the major functions of IgG? Providing immunity for the newborns because IgG can cross the placenta, fixing complement coating antigen for enhanced phagocytosis (opsonization), neutralizing toxins and viruses, and participating in agglutination and precipitation reactions (T or F) All subclasses of IgG appear to be able True to cross the placenta. What is the least efficient IgG? IgG2 What has FC receptors on their surfaces that are Macrophages, monocytes, and neutrophils specific for the FC region of IgG? What is the function of FC receptors? Enhances contact between antigen and phagocytic cells and increases the efficiency of phagocytosis What does IgG have that allows it to enter High diffusion coefficient extravascular spaces more readily than other Ig types? (T or F) IgG plays a major role in neutralizing True toxins and viruses. IgG is better at ____ reactions than at ____. Precipitation; agglutination 35 Immuno PPT Flashcards Unit 1 What does precipitation involve that are more easily brought together by relatively small IgG molecules? Small soluble particles What is defined as the clumping together of larger particles? Which Ig is much more efficient at agglutination than IgG? What is known as a macroglobulin? What has a sedimentation rate of 19S, which represents a molecular weight of approximately 970,000d? IgM accounts for ____% of all serum. What is the half-life og IgM? (T or F) IgM has a shorter half-life than IgG. What can IgM exist as? What is the difference between the pentamer and monomer form? When a pentamer forms, what holds the five monomeric units together? What is a glycoprotein with several cysteine residues? What do the cysteine residues serve as? Agglutination What is the shape of a IgM configured as a pentamer? How many functional binding sites are on a IgM? How many functionl binding sites are used on a IgM? The ____ valency of IgM antibodies contravenes the fact that they tend to have ____ affinity for antigen. Where is IgM mainly found? Which Ig cannot cross the placenta? What is the primary response antibody? What is the first Ig to appear after antigenic stimulation and the first to appear in the maturing infant? (T or F) IgM is synthesized only as long as antigen remains present. Are there memory cells for IgM? Which Ig is known as the secondary response? What is the primary response characterized by? IgM IgM Macroglobulin 5-10 10 days True Monomer or pentamer Pentamer form is found in secretions; monomer form occurs on the surface of B cells J (joining) chain J chain Linkage points for disulfide bonds between two adjacent monomers Starlike 10 5 High; low In the intravascular pool and not in other body fluids or tissues IgM IgM IgM True No IgG Long lag phase 36 Immuno PPT Flashcards Unit 1 What is the secondary response characterized by? What are the functions of IgM? Shortened lag period and much more rapid increase in antibody titer Complement fixation, agglutination, opsonization, and toxin neutralization What is the most efficient of all immunoglobulins at triggering the classical complement pathway? (T or F) IgM has multiple binding sites. The larger number of binding sites makes IgM more efficient at ____ reactions, especially with multivalent antigens. What does IgM form a potent defense against? Because IgM has a J chain, what can it occasionally acquire like IgA does? What does the IgM’s secretory component allow for? What does IgM serve as? What does the presence of membrane IgM classify lymphocytes as? What percentage of all circulation immunoglobulin is IgA? What is the molecular weight of the H chain? How much amino acids does the H chain consist of? What does IgA appear as? What is the approximate molecular weight of IgA? What are the two subclasses of IgA? How do IgA1 and IgA2 differ? How many amino acids are located in the hinge region and are deleted in IgA2? What makes IgA more resistant to? IgM Where is IgA2 predominately found? Where is IgA1 mainly found? IgA2 is found as a ____ along the respiratory, urogenital, and intestinal mucosa. What does IgA2 appear in? Since mucosal surfaces are a major point of entry for pathogens, what does IgA2 serve? What does the dimer consist of? How are the 2 monomers of the dimer held together? What is the molecular weight of the dimer? True Agglutination Many bacterial diseases Secretory component To traverse epithelial cells and patrol mucous membranes Surface receptor for antigen Mature B cells 10-15% Between 55,000-60,000 472 Monomer 160,000 IgA1 and IgA2 In content by 22 amino acids 13 Some bacterial proteinases that are able to cleave IgA1 In secretions at mucosal surfaces In serum Dimer Milk, saliva, tears, and sweat To keep antigen from penetrating further into the body 2 monomers J chain 15,000 37 Immuno PPT Flashcards Unit 1 Where is secretory IgA synthesized? What form is secretory IgA released in? What is the molecular weight of a secretory component? What is later attached to the FC region around the hinge portion of the alpha chain? How many immunoglobulin-like domains, does the secretory component consist of? Where is the secretory component derived from? What is the molecular weight of the SC precursor? Where is the SC precursor found? What does the SC precursor serve as? Plasma cells that secrete IgA actually home to ____ ____, where IgA ca bind as soon as it is released from the plasma cells. How are epithelial cells traversed? What occurs after trancytosis? What can the secretory component act to facilitate transport of? What does the secretory component make the dimer more resistant to? What is the main function of secretory IgA? How does secretory IgA act as first line defense? What is easily trapped in mucus and then eliminated by the ciliated epithelial cells of the respiratory and intestinal tracts? What does IgA appear not to be capable of? What may trigger the alternate complement pathway? What possess specific receptors for serum and secretory IgA? What triggers a respiratory burst and degranulation of the cell involved? What can both forms of IgA act as? What are opsonins? When was IgD discovered? In plasma cells found mainly in mucosalassociated lymphoid tissue Dimeric About 70,000 Secretory component Five Epithelial cells found in close proximity to the plasma cells 100,000 On the surface of epithelial cells A specific receptor for IgA Subeithelial tissue By transcytosis A small fragment of SC sttached to IgA is cleaved to liberate the IgA dimer with the remaining portion of the SC IgA to mucosal surfaces Enzymatic digestion by masking sites that would be susceptible to protease cleavage To patrol mucosal surfaces and act as a first line of defense Neutralizes toxins produced by microorganisms and helping to prevent bacterial adherence to mucosal surfaces Complexes of IgA and antigen Fixing complement by the classical pathway Aggregation of IgA immune complexes Neutrophils, monocytes, and macrophages Binding to the sites of IgA Opsonins Promoters of phagocytosis 1965 38 Immuno PPT Flashcards Unit 1 IgD was found in a patient with what disease? What is the percentage of IgD in the total serum? What is the molecular weight of IgD? What is the molecular weight of the H chain? What appears to have an extended hinge region consisting of 58 amino acids? Because of the unusually long hinge region, what is IgD more susceptible to? Multiple myeloma Less than 0.001% What is the half-life of IgD? Where are most of the IgD found? 2-3 days On the surface of immunocompetent but unstimulated B lymphocytes IgD What is the second type of immunoglobulin to appear? What may IgD play a role in? What makes IgD an ideal early responder to antigen? What do B lymphocytes bearing only IgM receptors appear incapable of? What are those with both IgM and IgD receptors capable of? (T or F) IgD may play a role in regulationg Bcell maturation and differentiation. In the secreted form in the serum, why doesn’t IgD appear to serve a protection function? Which immunoglobulin is the least abundant in the serum? What is the percentage of IgE in the total serum? What is composed of around 550 amino acids that are distributed over one variable and four constant domains? What cells produce IgE and are located primarily in the lungs and skin? Does IgE participate in typical immunoglobulin reactions such as complement fixation, agglutination, or opsonization? Is IgE incapable of crossing the placenta? What happens to IgE shortly after synthesis? What are the specific surface proteins called? Where are the high-affinity FC RI receptors found? 180,000 62,000 H chain Proteolysis B-cell activation High level of surface expression and its intrinsic flexibility IgG response Responding to T-cell help and switching to synthesis of IgG, IgA, or IgE True It does not bind complement, it does not bind neutrophils, or macrophages, and it does not cross the placenta IgE 0.0005% The H chain Plasma cells No Yes IgE attaches to basophils and tissue mast cells by means of specific surface proteins High- affinity FC RI receptors Basophils and tissue mast cells 39 Immuno PPT Flashcards Unit 1 Where does the IgE molecule bind at? Are the antigen-binding sites free to interact with specific antigen? Where are mast cells mainly found? How many receptors are on each mast cell? What happens when two adjacent IgE molecules on a mast cell bind specific antigen? What is induced when vasoactive amines are released? What is an allergic reaction called? What are examples of typical allergic reactions? What immunoglobulin serves a protective role by triggering an acute inflammatory reaction that recruits neutrophils and eosinophils to the area to help destroy invading antigens that have penetrated IgA defenses? What cells play a major role in the destruction of large antigens, such as parasitic worms, that cannot be easily phagocytized? What is the term for one of the first theories to be formulated in an attempt to explain antibody diversity in the early 1900s by Paul Ehrlich? (T or F) Paul Ehrlich postulated that certain cells had specific surface receptors for antigen that were present before contact with antigen occurred. What happened after an antigen was introduced and it would select the cell with the proper receptors? (T or F) Ehrlich’s side-chain theory laid the foundation for further hypotheses. In the 1950s, what idea did Niels Jerne and Macfarlane Burnet independently support? What is occurring when individual lymphocytes are genetically preprogrammed to produce one type of immunoglobulin and that a specific finds or selects those particular cells capable of responding to it, causing them to proliferate? Where are the surface immunoglobulins IgM and IgD found? What would repeated contact with antigen continually increase? CH3 domain on the FC region Yes In the skin and in the lining of the respiratory and alimentary tracts Several hundred thousand A cascade of cellular events is initiated that results in degranulation of the mast cells with release of vasoactive amines (histamine and heparin) Type 1 immediate hypersensitivity Type 1 immediate hypersensitivity Hay fever, asthma, vomiting and diarrhea, hives, and life-threatening anaphylactic shock IgE Eosinophils Side-chain theory True Combination would take place and then receptors would break off and enter the circulation as antibody molecules True A clonal selection process for antibody formation Clonal selection On immune-competent but unstimulated B lymphocytes A specific lymphocyte pool 40 Immuno PPT Flashcards Unit 1 What explains the kinetics of the immune response? Who proposed a solution to the tissue of the large number of genes required by the clonal selection theory? What did Dryer and Bennett suggest? Clonal selection There could be a small number coding for the ____ region and a larger number coding for the ____ region. What happens within lymphocytes? What controls synthesis of a particular immunoglobulin, and through a random selection process these individual segments are joined to commit that lymphocyte to making antibody of a single specificity? (T or F) B cells are genetically preprogrammed to synthesize very specific antibody. What antibodies are used for diagnostic testing and for therapeutic purposes? Why is the normal response to antigen heterogeneous? In 1975, what did Georges Kohler and Cesar Milstein discover? In Kohler and Milstein’s technique, what is fused with an activated B cell? What is a myeloma cell? (T or F) Plasma cells normally produce antibody. What kind of cell line is chosen for the Kohler and Milstein’s technique? What enzyme is deficient in the cell line that is not capable of producing antibody? What enzyme is incapable of synthesizing nucleotides from hypoxanthine and thymidine, which are needed for DNA synthesis? What cells are harvested after a mouse is immunized with a certain antigen? What cells are combined in the presence of polyethylene glycol (PEG), a surfactant? What is produced when the PEG brings about fusion of plasma cells with myeloma cells? (T or F) In hybridoma production, only a small percentage of cells actually fuse and some of Constant; variable Dryer and Bennett The constant and variable portions of immunoglobulin chains are actually coded by separate genes Genetic rearrangements More than one gene True Monoclonal antibodies A purified antigen has multiple epitopes that stimulate a variety of B-cell clones A technique to produce antibody arising from a single B cell A myeloma cell A cancerous plasma cell True A particular cell line that is not capable of producing antibody Hypoxanthine guanine phosphoribosyl transferase (HGPRT) Hypoxanthine guanine phosphoribosyl transferase (HGPRT) Spleen cells Spleen and myeloma cells Hybridoma True 41 Immuno PPT Flashcards Unit 1 these are two meloma cells or two spleen cells. After fusion and cells are placed in culture, what is contained in the selective medium used? What is the culture in the HAT medium used to separate? What can hybridoma cells synthesize? Why is one pathway, which builds DNA from degradation of old nucleic acids, blocked? The other pathway, which makes DNA from new nucleotides, is blocked by what? In hybridoma production, what cells normally die out? What cells have the ability (acquired from the myeloma cell) to reproduce indefinitely in culture and the ability (acquired from the B cell) to synthesize nucleotides by the HGPRT and thymidine kinase pathway? What antibodies were initially used for in vitro diagnostic testing and in delivering therapeutic agents in a variety of diseases? Define cytokines in two parts. Cytokines are chemical messengers. several different cell types produce them. True or False? Cytokines have activity modulating effects. They affect ___________ and ___________ systems. They act through through activation of cell-bound receptor proteins. Induce means__________________. Cytokines are induced in response to specific stimuli. Clarify some example stimuli. Be Specific. Cytokines can scale to effect: Hypoxanthine, aminopterin, and thymidine (HAT) Hybridoma cells by allowing them to grow selectively Nucleotides in the HAT medium The myeloma cell line employed is deficient in the required enzymes HGPRT and thymidine kinase Presence of aminopterin in the medium Myeloma cells and normal B cells Fused hybridoma cells Monoclonal antibodies Cytokines are small soluble proteins that regulate the immune system’s innate immunity. They are the adaptive response to infection. True Hematopoietic and immune systems to bring about, produce, or cause to stimulate the synthesis of (a protein,especiall y an enzyme) by increasing gene transcription. bacterial lipopolysaccharides (Lipid A), flagellin, and other bacterial products. regulation of growth, differentiation gene expression many different cell types including leukocytes are effected 42 Immuno PPT Flashcards Unit 1 Define autocrine stimulation. Define paracrine stimulation. Do cytokines exert systemic or endocrine activities always? True or False? Elaborate the stages of basic cytokine production by host lymphocytes Cytokines act individually and separately. True or False? What is the result of cytokine expression. Clarify. What is a cytokine cascade What often determines the outcome and the clinical course of infection? Massive overproduction plus deregulation in the immune system creates a cytokine storm. What terminal effects can be expected? The cytokines include major families. What are some major families available for study today. An Interleukin is a _________ cytokine. For the cytokines to be classified as interleukins. What are the three criteria they must satisfy? Interleukins are numbered… IL-1 to IL-32 Cytokines were originally thought to act solely on cells of the immune system. What new discovery was made about them? Pleiotropic means… Can many different cytokines share their properties? Many cytokines share receptors. Illustrate some of the effects or activities. Name two clinical uses of cytokines. What conditions could the two variants of affecting the same cell that secreted it affecting a target cell in close proximity False, only occasionally do they do so the ligation of cell adhesion molecules the recognition of foreign antigens False; they do not act alone, but in concert with many others that are induced during the process of immune activation. A network is formed regulating leukocyte activity. The cytokine cascade produces a spectrum of activities that lead to the rapid generation of innate and adaptive immune responses. the ability or inability to generate certain cytokine patterns shock, multi-organ failure, or even death. tumor necrosis factors (TNF), interferons (IFN), chemokines, transforming growth factors (TGF), and colony-stimulating factors (CSF), interleukins(IL) unrelated They must have had their genes cloned. They must be inducible in leukocytes. Their biological activities in inflammatory processes must be cataloged. IL-1 to IL-32 They may also act on cells outside the immune system. Having many effects ie The nature of cytokine activity relates to: the widespread distribution of cytokine receptors on many cell types, and the ability of cytokines to alter expression of numerous genes. Yes, they activate some of the same pathways and genes. Some may have overlapping effects. Some may alter the activity of many of the same genes. cytokine antagonists cytokine receptor antagonists rheumatoid arthritis, psoriasis, asthma, Crohn's 43 Immuno PPT Flashcards Unit 1 cytokines be usable for? Will there be future demands placed on the labs for cytokine assays. The patterns of cytokine expression can determine… A patient has presented defects in the cytokines or their receptors/signal transduction circuits. What possible illnesses could be a play in the patient’s body? What sort of analyses are recommended for the patient above? Inflammation due to the body’s innate immune response has several criteria. Name four. The innate immune response is___________ but occurs within hours of first contact with microorganisms . What is the main function of the innate immune response? Choose several cytokines involved in innate immune response. IL-1 has 2 subtypes plus 1 antagonist. IL-1α facts IL-1β facts IL-1 facts disease, transplantation, and cancer treatments Defenitely whether the host will be able to mount an effective defense against and survive certain infections. Numerous immunodeficiency syndromes and leukemias are theoretically possible. Genetic and Proteomics. Assess treatment modalities, effectiveness, and potential gene replacement therapies fever, swelling, pain, and cellular infiltrates into damaged tissues. nonspecific To recruit effector cells to area. interleukin-1, tumor necrosis factor-α, interleukin-6 chemokines, transforming growth factor-β, and interferons, both α and β. IL-1α, IL-1β, and IL-1RA (IL-1 receptor antagonist) Proinflammatory monocytes and macrophages requires the presence of microbial pathogens, bacterial lipopolysaccharide's, or other cytokines. Intracellular can be released after cell death can help attract inflammatory cells to areas where cells and tissues are being killed or damaged. is responsible for most of the systemic activity fever activation of phagocytes production of acute phase proteins is secreted by monocytes endogenous pyrogen induces fever(acute phase response) acts on the hypothalamus(thermostat) hypothalamus resets body temp to higher level bacterial and viral growth is inhibited 44 Immuno PPT Flashcards Unit 1 IL-1 facts part 2 lymphocyte activity is increased induces the production of vascular celladhesion molecules chemokines and IL-6 production are increased Also induces the production of colony stimulating factors in the bone marrow, thereby increasing the available number of phagocytic cells that can respond to the damaged tissues Define diapedesis a process, Chemokines and cell-adhesion molecules attract and assist leukocytes to enter the inflamed area. IL-1RA facts produced by monocytes and macrophages acts as an antagonist to IL-1 blocks the IL-1 receptor limits the availability of the receptor for IL-1 turns off the response to IL-1 when no longer needed Tumor necrosis factor-α (TNF-α) fact sheet first isolated from tumor cells induce lysis in tumor cells the most prominent member of the TNF superfamily at least 19 different peptides that have diverse biological functions. both membrane-bound and soluble forms causes vasodilation increased vasopermeability lipopolysaccharide is the main trigger from gram-negative bacteria secreted by activated monocytes and macrophages activate T cells through its ability to induce expression of MHC class II molecules enhances antigen presentation activates T cells secreted at high levels, TNF can have deleterious systemic effects septic shock can result large amounts of TNF secreted in response to gram-negative bacterial infections, causing a decrease in blood pressure, reduced tissue perfusion, and disseminated intravascular Tumor necrosis factor-α (TNF-α) fact sheet II Tumor necrosis factor-α (TNF-α) fact sheet III major drawbacks 45 Immuno PPT Flashcards Unit 1 Where can TNF-α be found? TNF-α has a major role in inflammatory illnesses. Name 2. IL-6 fact sheet Where is IL-6 produced? Chemokines fact sheet coagulation. uncontrolled bleeding present in rheumatoid synovial fluids and synovial membranes Crohn’s disease, with rheumatoid arthritis (RA) a single protein triggered by lipopolysaccharide a pleiotropic cytokine Affects the inflammation, acute phase reactions, immunoglobulin synthesis, and the activation states of B cells and T cells. Stimulates B cells to proliferate and differentiate into plasma cells. Induces CD4+ T cells to produce greater quantities of both pro- and anti-inflammatory cytokines. Chemokines facilitate the extravasation of leukocytes into the tissues in areas of inflammation. facilitate the migration of leukocytes into the tissues activate integrins Allow for the co--localization of multiple cell types to the damaged tissue Help to broaden the response to tissue damage. Enable the leukocytes to migrate between the endothelial cells. The gradient of concentration is important to leukocytes that chemokines can make. abnormal receptors have some protection from the HIV virus lymphoid and nonlymphoid cells, including a variety of normal and transformed cells: T cells, B cells, monocytes and macrophages, fibroblasts, hepatocytes, keratinocytes, astrocytes, vascular endothelial cells, and various tumor cells. family of cytokines that enhance motility Are classified into four families based on the position of N-terminal cysteine residues. 40 known chemokines 46 Immuno PPT Flashcards Unit 1 Define chemotaxis? A process that promotes migration of many types of white blood cells toward the source of the chemokine. Chemokines regulate leukocyte activities include the response to infectious diseases, autoimmune inflammation, cancer, and the homing of lymphocytes to all the lymphoid tissues. Identify the four chemokine groups and state the alpha, or CXC, chemokines—contains a single differences. amino acid between the first and second cysteines. beta, or CC, chemokines—has adjacent cysteine residues. C chemokines—lacks one of the cysteines. CX3C—has three amino acids between the cysteines. What are chemokines’ key roles in numerous disease processes? Initiation, development of inflammatory processes. Chemokine drawbacks. Chemokine receptors are utilized by the HIV virus to gain access to the cell. composed of three isoforms: TGF-β1, β2, and β3 Induced growth arrest in tumor cells in early studies. Induces antiproliferative activity inhibits the activation of macrophages anti-inflammatory factor for mature T cells. production by helper T cells important factor in the establishment of oral tolerance to bacteria normally found in the mouth. autocrine regulator to limit the expansion of activated cells cell growth differentiation apoptosis, migration, the inflammatory response Transforming growth factor beta (TGF-β) fact sheet When active TGF-β regulates…. 47 Immuno PPT Flashcards Unit 1 Type I interferons can interfere with___________. Especially IFN-α and IFN-β. What cells produce interferons? Interferons induce…. Type I IFN can activate__________. Type I IFN enhances ____________. Type I IFN works against… Cytokines involved in the _____________are mainly secreted by T cells, especially T helper (Th) cells, and affect T- and B-cell function more directly than was the case with cytokines in the innate immune response. helps down-regulate the inflammatory response when no longer needed viral replication dendritic cells The production of proteins and pathways that directly interfere with viral replication and cell division. natural killer cells The expression of MHC class I proteins, thus increasing the recognition and killing of virusinfected cells. certain malignancies and other inflammatory processes adaptive immune response There are three main subclasses of Th cells. Identify them. Th1, Th2, and Treg (T regulatory cells). What is the function of the T-cell receptor? Captures antigens and is a target of clonal expansion of CD4+ T helper cells. induce high-level expression of IFN-γ. Th1 cells also secrete IL-2. IL-2 a. T-cell growth factor b. drives the growth and differentiation of both T and B cells c. and induces lytic activity in NK cells d. can activate proliferation of Th2 cells e. helps to generate IgG1- and IgEproducing cells Th1 cell factsheet IL12 fact sheet IFN-γ fact sheet produced by macrophages and B cells multiple effects on both T cells and natural killer (NK) cells responds to certain stimuli, such as mycobacteria, intracellular bacteria, and viruses increases the cytolytic ability of natural killer (NK) cells. the principal molecule produced by Th1 cells It affects the RNA expression levels of more than 200 genes. 48 Immuno PPT Flashcards Unit 1 Th2 cell factsheet IL-10 fact sheet Tregs fact sheet stimulates antigen presentation by MHC I and MHC II molecules regulates theactivation of CD4+ Th1 cells, CD8+ cytotoxic lymphocytes, NK cells, bactericidal activities, IL-12R, and IL-18R primarily responsible for antibody-mediated immunity produced by monocytes, macrophages, CD8+ T cells, and Th2 CD4+ T cells It inhibits antigen presentation by macrophages stimulates CD8+ T cells allergies, autoimmune diseases, fighting off parasites anti-inflammatory and suppressive effects onTh1 an antagonist to IFN-γ down-regulator of the immune response. CD4+ CD25+ T cells Thymus is their home. Play a key role in establishing peripheral tolerance to a wide variety of self-antigens, allergens, tumor antigens, transplant antigens, and infectious agents. Effected by Foxp3 a transcription factor that causes Treg cells to suppress the activity of other T cells. Name the colony stimulating factors(CSF). colony stimulating factors(CSF) fact sheet Erythropoietin (EPO) fact sheet Erythropoietin can improve __________. Which one is not a symptom of endotoxic Responsible for inducing IL-10 and TGF-β expression in adaptive T regulatory 1 (Tr1) cells in the peripheral circulation. prevent chronic inflammation. IL-3 EPO erythropoietin G-CSF granulocye M-CSF macrophage GM-CSF granulocyte act on bone marrow cells and promote specific colony formation for the various cell lineages. regulates RBC production in the bone marrow primarily produced in the kidneys oxygenation of the tissues Dypsia is not a mechanism of Endotoxic Shock. 49 Immuno PPT Flashcards Unit 1 shock? A. DIC B. Multi-organ failure C. Nuetropenia D. Dypsia What is the Complement immune system? Where does the compliment protein synthesis? How does the complement system get activated? D is the answer • Complement is a complex series of more than 30 soluble and cell-bound proteins that interact in a very specific way to enhance host defense mechanisms against foreign cells. • It was named by Paul Ehrlich because it complements the action of antibody in destroying microorganisms. • While complement promotes opsonization and lysis of foreign cells and immune complexes, chronic activation can lead to inflammation and tissue damage. It is the latter that occurs in autoimmune diseases; therefore, complement activation needs to be carefully regulated in order to minimize tissue damage. In addition to the major proteins involved in activation, there are numerous proteins that act as controls or regulators of the system. The three pathways for activation of complement will be discussed along with major system controls. • Most plasma complement proteins are synthesized in the liver, with the exception of C1 components, which are mainly produced by intestinal epithelial cells, and factor D, which is made in adipose tissue. • Other cells, such as monocytes and macrophages, are additional sources of early complement components, including C1, C2, C3, and C4. • Most of these proteins are inactive precursors, or zymogens, which are converted to active enzymes in a very precise order (see Table 6-1). The complement system can be activated in three different ways • The first is the classical pathway, which involves nine proteins that are triggered 50 Immuno PPT Flashcards Unit 1 • • • • • What are the roles of the complement in the immune defense system? • • • • • What is the immune classic pathway? • by antigen–antibody combination. The second pathway, the alternative pathway, is an antibody-independent means of activation of complement. The third pathway, the lectin pathway, is another antibody-independent means of activating complement proteins. Its major constituent, mannose- (or mannan-) binding lectin (MBL), adheres to mannose found mainly in the cell walls or outer coating of bacteria, viruses, yeast, and protozoa. Complement activation seldom involves only one pathway. The complement system plays a major part in the inflammatory response directed against foreign antigens. Although the end product of complement activation is lysis of the invading cell, many other important events take place along the way. Complement fragments act as opsonins, for which specific receptors are present on phagocytic cells, thus enhancing the metabolism and clearance of immune complexes. In fact, uptake of immune complexes in the spleen appears to be complementdependent. Complement components are also able to increase vascular permeability, recruit monocytes and neutrophils to the area of antigen concentration, and trigger secretion of immunoregulatory molecules that amplify the immune response. Any deficiencies in the complement system can result in an increased susceptibility to infection or in the accumulation of immune complexes with possible autoimmune manifestations. The classical pathway, or cascade, is the 51 Immuno PPT Flashcards Unit 1 How does the IgG play a role in the classic pathway? What are the other substances that can bind complement directly to initiate the classical cascade? How many stages can the complement activation can be divided and what are they? main antibody-directed mechanism for triggering complement activation. • IgM, IgG1, IgG2, and IgG3 are capable of activation through the classical pathway. • IgM is the most efficient, because it has multiple binding sites; thus, it takes only one IgM molecule attached to two adjacent antigenic determinants to initiate the cascade. • Two IgG molecules must attach to antigen within 30 to 40 nm of each other before complement can bind, and it may take at least 1,000 IgG molecules to ensure that two are close enough to initiate such binding. • Within the IgG group, IgG3 is the most effective, followed by IgG1 and then IgG2. • Some epitopes, notably the Rh group, are too far apart on the cell for this to occur, so they are unable to fix, or activate, complement. • In addition to antibody, there are a few substances that can bind complement directly to initiate the classical cascade. • These include C-reactive protein, several viruses, mycoplasmas, some protozoa, and certain gram-negative bacteria, such as E. coli. • However, most infectious agents can directly activate only the alternative pathway. • • • • • Complement activation can be divided into three main stages, each of which is dependent on the grouping of certain reactants as a unit. The first stage involves C1, which is known as the recognition unit. Once C1 is fixed, the next components activated are C4, C2, and C3, known collectively as the activation unit. C5–C9 comprise the membrane attack complex, and it is this last unit that completes lysis of the foreign particle. Figure 6-1 depicts a simplified scheme of 52 Immuno PPT Flashcards Unit 1 the entire pathway. What is the first recognition unit in the complement complex? • • • What is the shape and the function of the Clq in the complement complex? • • • • • What is the function of the Clq in recognizing antibodies? • What are the Clr and the Cls and how are they activated? • • • • The Recognition Unit: C1qrs The first complement component to bind to the cell membrane of the bacterium or other cell to be destroyed is C1, which consists of three subunits: Clq, Clr, and Cls, which are stabilized by calcium. The complex is made up of one Clq subunit and two each of the Clr and Cls subunits. The (Clr, Cls)2 complex is an S-shaped structure with several domains of unequal size. It is hypothesized that this structure assumes the shape of a distorted figure eight, and it wraps itself around the arms of Clq (see Fig . 6-2). Clq has a molecular weight of 410,000 and is composed of six strands that form six globular heads with a collagen-like tail portion. This structure has been likened to a bouquet with six blossoms extending outward (see Fig. 6-2). Each of the six “stalks” is composed of three homologous polypeptide chains—A, B, and C—that form a triple helix. Clq “recognizes” the fragment crystallizable (FC) region of two adjacent antibody molecules, and at least two of the globular heads of Clq must be bound to initiate the classical pathway. Clr and Cls are both serine protease proenzymes or zymogens; as binding of Clq occurs, both are converted into active enzymes. Autoactivation of Clr results from a conformational change that takes place as Clq is bound. Mechanical stress transmitted from the stems as binding occurs opens up the active site on Clr. Once activated, Clr cleaves a thioester 53 Immuno PPT Flashcards Unit 1 • • • What is phase 2 of the activation unit and what does it produce? • • • • • • • How is C2 cleaved and form C2a? • • How is C2 converted to C4b and how will they form the C3 convertase? • • bond on Cls, which activates it. Activated Clr is extremely specific, because its only known substrate is Cls. Cls has a limited specificity, with its only substrates being C4 and C2. Once Cls is activated, the recognition stage ends. Phase 2, the formation of the activation unit, results in the production of an enzyme known as C5 convertase. Cls cleaves C4 to split off a 77-amino acid fragment called C4a. In the process, it opens a thioestercontaining active site on the remaining part, C4b. C4b must bind to protein or carbohydrate within a few seconds, or it will react with water molecules to form iC4b, which is rapidly degraded. Thus, C4b binds mainly to antigen in clusters that are within a 40 nm radius of C1. This represents the first amplification step in the cascade, because for every one C1 attached, approximately 30 molecules of C4 are split and attached. C2 is the next component to be activated. When combined with C4b in the presence of magnesium ions, C2 is cleaved by Cls to form C2a (which has a molecular weight of 70,000) and C2b (which has a molecular weight of 34,000) (see Fig. 63A). This is the only case for the designation “a” to be given to the cleavage piece with enzyme activity (see Fig. 6-1). Binding of C2 to C4b can occur in the fluid phase, but C4b attached to antigen is much more efficient in accepting C2. This serves to keep the reaction localized. The combination of C4b and C2a is 54 Immuno PPT Flashcards Unit 1 • • • How does C3 important in the activation pathway and what is it's structure? • • • • After the cleavage of C3, what are the amplification processes? • • • • • • The membrane attack complex is which phase known as C3 convertase (see Fig. 6-3B). This is written as C4b2a to indicate that the complex is an active enzyme. The half-life is estimated to be between 15 seconds and 3 minutes, so C3 must be bound quickly. If binding does occur, C3 is cleaved into two parts, C3a and C3b. C3 serves as the pivotal point for all three pathways, and cleavage of C3 to C3b represents the most significant step in the entire process of complement activation. C3 consists of two polypeptide chains, alpha and beta. The alpha chain contains a highly reactive thioester group, and when C3a is removed by cleavage of a single bond in the α chain, the thioester is exposed. The remaining piece, C3b, is then capable of binding to hydroxyl groups on carbohydrates and proteins in the immediate vicinity. The cleavage of C3 represents a second and major amplification process, because about 200 molecules are split for every molecule of C4b2a. In addition to being required for the formation of the membrane attack complex, C3b also serves as a powerful opsonin. Macrophages have specific receptors for C3b. However, a large number of molecules are needed for this to occur; hence the need for amplification. If C3b is bound within 40 nm of the C4b2a, then this creates a new enzyme known as C5 convertase. Figure 6-3C depicts this last step in the formation of the activation unit. Phase 3 55 Immuno PPT Flashcards Unit 1 of the complement cascade? The cleaving of C5 with deposition of C5b at another site on the cell membrane constitutes the beginning of the? What consists of two polypeptide chains, α and β, which are linked by disulfide bonds? C5 convertase consists of what? C5 convertase splits into what? C5b attaches to what, forming the beginning of the MAC? What is extremely labile, and it is rapidly inactivated unless binding to C6 occurs? C6, C7, C8, and C9 do not have what? Membrane damage is caused by what two different mechanisms? What causes a reordering and reorientation of molecules that results in leaky patches? When complement proteins are bound, membrane phospholipids rearrange themselves into domains surrounding the C5b6789 complex causing what? What is able to pass freely out of the cell? The membrane attack unit begins when? C6 does what when it binds to C5b? What attaches to the cell surface? What binds to C5b6 forming a trimolecular complex that has a high affinity for lipid constituents of the cell membrane? What allows for insertion of the C7 part of the C5b67 complex into the membrane of the target cell? What binds to C7 and exposes a hydrophobic region that interacts with the cell membrane to form a small hole in the membrane? Which protein is inserted into the lipid bilayer? Lysis can be observed after which protein binds? Which protein accelerates the lysis process? Binding of C8 causes a loss of what from the cell? What follows the leakage of potassium from the cell? What polymerizes only when bound, and it is believed that the C5–C8 complex acts as a catalyst to enhance the rate of reaction? What forms a hollow, thin-walled cylinder, membrane attack complex (MAC) C5 C4b2b3b C5a and C5b the cell membrane C5b enzymatic activity channel formation and the binding of phospholipids the binding of phospholipids the integrity of the membrane to be destroyed Ions C6 binds to C5b It stabilizes it The C5bC6 complex C7 The binding of C7 C8 C8 C8 C9 potassium The leakage of amino acids and ribonucleotides C9 Polymerized C9 56 Immuno PPT Flashcards Unit 1 which constitutes the transmembrane channel? Pathogens can be destroyed in the absence of antibody in which pathway? Which pathway acts as part of innate or natural immunity? Which pathway was originally named for the protein properdin? What does not initiate this pathway but rather stabilizes the C3 convertase formed from activation of other factors? The alternative pathway does not involve which proteins? Which pathway has to get to C3 without going through C2 and no C4 and without antibodies? Some Ag’s, like LPS, directly trigger a little of which protein to be cleaved? Which protein is unstable, and is the pivotal molecule to activate? What protein acts on factor B? What acts on Bb to create C3Bb? What binds to host cells to prevent lysis and inhibits C3 activation? What •is a FACTOR that becomes a SUBSTRATE, which acts as an ENZYME on C3, as part of a complex? What are the proteins that are unique to the alternative pathway? Bacterial cell walls, especially those containing lipopolysaccharide, fungal cell walls, yeast, viruses, virally infected cells, tumor cell lines, and some parasites, especially trypanosomes are substances that trigger which pathway? Bacterial cell walls, especially those containing lipopolysaccharide, fungal cell walls, yeast, viruses, virally infected cells, tumor cell lines, and some parasites, especially trypanosomes can serve as sites for binding what? What is the first step in the alternative pathway? In plasma, which protein is not stable? Water is able to hydrolyze a thioester bond and thus spontaneously activate a small number of which molecules? Once activated, C3 can bind to what in the alternative pathway? Binding of C3b to B causes a conformational change that makes B more susceptible to the alternative pathway the alternative pathway the alternative pathway Properdin C2 and C4 the alternative pathway C3 C3 C3b Factor D Factor H Properdin (Factor P) Properdin, factor B and factor D The alternative pathway C3bBb The conversion of C3 native C3 C3 factor B serine proteases 57 Immuno PPT Flashcards Unit 1 cleavage by what? Bound factor B can be cleaved by which factor? Factor D is a plasma protein that goes through a conformational change when it binds to what factor? Factor D’s only substrate is bound to which factor? What protein cleaves factor B into two pieces: Ba and Bb? What complex forms the initial C3 convertase of the alternative pathway? C3bBb is then capable of cleaving what protein? C3Bb creates an amplification loop that feeds C3b into which pathway(s)? The enzyme C3bBb is extremely unstable unless what binds to the complex? C3bBb can also cleave what protein, but it is much more efficient at cleaving C3.? Which enzyme has a high affinity for C5 and exhibits C5 convertase activity? What is the first part of the membrane attack unit? Both the alternative and classical pathways are identical from the cleavage of which protein? Which pathway provides link between the innate and acquired immune response? Which pathway involves nonspecific recognition of carbohydrates that are common constituents of microbial cell walls and that are, importantly, distinct from those found on human cell surfaces? What proteins bind to carbohydrates? What binds to mannose or related sugars in a calcium-dependent manner to initiate the lectin pathway? What are found in glycoproteins or carbohydrates of a wide variety of microorganisms, such as bacteria, yeasts, viruses, and some parasites? What is a component of many fungi (those which contain chitin, which is composed of mannose), protozoa, and some bacteria (those which have unusual LPS, OPS, or capsules with mannose)? What is considered an acute phase protein, factor D factor B factor B factor D C3Bb C3 the classical and alternative pathways properdin C5 C3bBb3bP C5b C5 to make C5b lectin pathway lectin pathway Lectins mannose-binding, or mannan-binding, lectin (MBL) sugar Mannose mannan-binding lectin (MBL) 58 Immuno PPT Flashcards Unit 1 because it is produced in the liver and is normally present in the serum but increases during an initial inflammatory response? Deficiencies of MBL have been associated with what serious infections? The structure of what is similar to that of C1q? MBL is associated with which proteases? MBL binds to what cellular surface structure? What is homologous to C1s and causes auto activity? What takes the active role in cleaving C4 and C2? The functions of which MASPs are unclear at this time. Once C4 and C2 are cleaved, the rest of the lectin pathway is identical to which pathway? All complement pathways produce which proteins? Which proteins are released in a gradient that increases as it gets closer to the source? What is also an anaphylaxis protein, constricts blood vessels to prevent spread? What cells in the area have receptors (C3aR and C5aR) on their surface? What signals the nucleus that they have been activated? What happens after the receptors signal the nucleus that they have been activated? What is intentional direction movement by chemonavigation UP the gradient called? On the way to the bacteria, the phagocyte will begin to express what? What causes the neutrophils to stick weakly to the host epithelium so they can creep along the surface of the epithelium, seeking its target? What causes the neutrophils to squeeze through the blood vessel wall (DIAPEDESIS) to get to the bacteria? What ensures that infectious agents and not selfantigens are destroyed and that the reaction remains localized? Why are the majority of the control proteins acts to halt accumulation of C3b? Which is a glycoprotein that inhibits activation at the first stages of both the classical and lectin neonatal pneumonia and sepsis mannan-binding lectin (MBL) three MBL-serine proteases (MASPs): MASP1, MASP-2, and MASP-3 MASP-2 MASP-2 MASP-2 MASP-1 and MASP-3 Classical pathway C3a and C5a C3a and C5a C5a Phagocytes receptors Cytoskeletal Reorganization vector motility Adhesion molecule receptors Selectons Integrins plasma proteins Because activation of C3 is the pivotal step in all pathways C1 inhibitor, or C1INH 59 Immuno PPT Flashcards Unit 1 pathways? What glycoprotein’s main role is to inactivate C1 by binding to the active sites of C1r and C1s? What remains bound to the antibody, but all enzymatic activity ceases when C1 inhibitor, or C1INH binds? What inactivates MASP-2 binding to the MBLMASP complex, thus halting the lectin pathway? Soluble C4b-binding protein (C4BP) and three cell-bound receptors, complement receptor type 1 (CR1), membrane cofactor protein (MCP), and decay accelerating factor (DAF) all inhibit what? What is a serine protease that inactivates C3b and C4b when bound to one of these regulators? Once bound to CR1, both C4b and C3b can then be degraded by? What also acts as a receptor on platelets and red blood cells and to mediate transport of C3bcoated immune complexes to the liver and spleen? What is the most efficient cofactor for factor I– mediated cleavage of C3b? How does MCP also help to control the alternative pathway? What is capable of dissociating both classical and alternative pathway C3 convertases? What portion of DAF is covalently attached to a glycophospholipid anchor that is inserted into the outer layer of the membrane lipid bilayer? What is the reason that DAF can reach C3 convertase sites that are not immediately adjacent to it? What is the reason that the presence of DAF on host cells protects them from bystander lysis and is one of the main mechanisms used in discrimination of self from nonself? What is the principal soluble regulator of the alternative pathway? Which factor acts by binding to C3b, thus preventing the binding of factor B? C3b in the fluid phase has a hundredfold greater affinity for which factor than for factor B? On cell surfaces, C3b preferentially binds which C1 inhibitor, or C1INH C1q C1 inhibitor, or C1INH formation of C3 convertase in the classical and lectin pathways factor I factor I CR1 MCP Since binding of factor B to C3b is inhibited DAF The carboxy-terminal arrangement of DAF in the lipid bilayer allows DAF mobility within the membrane because foreign cells do not possess DAF factor H factor H factor H Factor B 60 Immuno PPT Flashcards Unit 1 factor? Which factor accelerates the dissociation of the C3bBb complex on cell surfaces? Which factor acts as a cofactor that allows factor I to break down C3b Which protein is also known as vitronectin? Which protein interacts with the C5b67 complex as it forms in the fluid phase and prevents it from binding to cell membranes? What causes binding of C8 and C9 to still proceed, but polymerization of C9 does not occur, and the complex is unable to insert itself into the cell membrane or to produce lysis? What also acts to block formation of the membrane attack complex besides S protein? What protein’s main function is to bind to C8 and prevent insertion of C9 into host cell membranes? What protein plays an important role as part of the B-cell coreceptor for antigen? What acts with CD19, and binds complementcoated antigen and cross-links it to membrane immunoglobulin to activate B cells? What are more effective at enhancing B-cell differentiation and production of memory cells than is antigen by itself? What cell surface molecule is found on monocytes, macrophages, neutrophils, and natural killer cells, specifically binds particles opsonized with iC3b, a C3b degradation product? What receptor plays a key role in mediating phagocytosis of particles coated with these complement fragments? Patients whose white blood cells lack CR3 receptors fail to exhibit functions such as: What proteins are found on neutrophils, monocytes, tissue macrophages, activated T cells, dendritic cells, NK cells, and activated B cells? What proteins’ function appears to be similar to that of CR3, and they may assist neutrophil adhesion to the endothelium during inflammation? What proteins also serve as a means of linking innate and natural immunity? Factor H Factor H S protein S protein S protein Membrane inhibitor of reactive lysis (MIRL), or CD59 Membrane inhibitor of reactive lysis (MIRL), or CD59 CR2 CR2 Immune complexes CR3 (CD11b/CD18) CR3 chemotaxis, surface adherence, and aggregation CR4 CR4 Complement proteins 61 Immuno PPT Flashcards Unit 1 What is a small peptide that causes increased vascular permeability, contraction of smooth muscle, and release of histamine from basophils and mast cells? C3a, C4a, and C5a are classified as? What also serves as a chemotaxin for neutrophils, basophils, eosinophils, mast cells, monocytes, and dendritic cells What type of molecules direct neutrophils, basophils, eosinophils, mast cells, monocytes, and dendritic cells to the source of antigen concentration? Which molecules facilitate phagocytosis and clearance of foreign substances? What can be harmful if (1) activated systemically on a large scale, as in gramnegative septicemia, (2) it is activated by tissue necrosis such as myocardial infarction, or (3) lysis of red cells occurs? Lysis may be another end result of complement activation, such as in what? What usually manifests itself in increased susceptibility to infection and delayed clearance of immune complexes? Most of these complement protein conditions are inherited on an autosomal recessive gene, and they are quite rare, occurring in what percent of the general population? A second deficiency that occurs with some frequency is that of mannose-binding lectin, found in what percent of the population? Lack of what has been associated with pneumonia, sepsis, and meningococcal disease in infants? The most serious deficiency is of what, because it is the key mediator in all pathways? Individuals with paroxysmal nocturnal hemoglobinuria (PNH) have red blood cells that are deficient in what? Some studies indicate that a DAF deficiency is associated with a lack of what? A deficiency in the what of the DAF molecule prevents its insertion into the cell membrane? What prevents insertion of C9 into the cell membrane by binding to the C5b678 complex, thus inhibiting formation of transmembrane anaphylatoxin anaphylatoxin C5a chemotaxin C4b, C3b, and iC3b Complement cold autoimmune hemolytic anemia Hereditary deficiency of any complement protein 0.03% 3 – 5% MBL C3 DAF CD59 (MIRL) glycophospholipid anchor CD59 62 Immuno PPT Flashcards Unit 1 channels? Recurrent attacks of angioedema that affect the extremities, skin, gastrointestinal tract, and other mucosal surfaces are characteristic of? What results in excess cleavage of C4 and C2, keeping the classical pathway going and creating kinin-related proteins that increase vascular permeability? What are the methods most frequently used to assay individual complement components? Assays are available for Clq, C4, C3, C5, factor B, factor H, factor I, C1 inhibitor, and C3a, C4a, and C5a, but what can they not tell about the factors? What is most commonly used to measure lysis, the end point of complement activation, as a functional test of complement activity? What test measures the amount of patient serum required to lyse 50 percent of a standardized concentration of antibody-sensitized sheep erythrocytes? The CH50 titer is expressed in what kind of units, which is the reciprocal of the dilution that is able to lyse 50 percent of the sensitized cells? What is defined as when the change in lytic activity per unit change in complement is at a maximum? What has been designed as another means of measuring activation of the classical pathway? In ELISA assays, what attaches to solid-phase IgM attached to the walls of microtiter plates? Antihuman antibody to C9 conjugated to alkaline phosphatase is the indicator of what? Alternative pathway activation by means of what assay? In the AH50 assay what results from the buffer system that chelates calcium? What can detect C3bBbP or C3bP complexes? (1) Decreased production, (2) increased in vivo consumption, or (3) in vitro consumption can lead to what levels of complement components or activity? A typical screening test for complement abnormalities includes testing for which protein/factor levels? What occurs after the binding of antigen and hereditary angioedema deficiency or lack of C1INH radial immunodiffusion (RID) and nephelometry whether the molecules are functionally active The hemolytic titration (CH50) assay The hemolytic titration (CH50) assay CH50 units The 50 percent point ELISA assays Patient complement complement activation AH50 assay The blocking of classical pathway activation ELISA assays Decreased levels of complement components or activity C3, C4, and factor B levels Complement fixation 63 Immuno PPT Flashcards Unit 1 antibody, with uptake of complement, can be used as an indicator of the presence of either specific antigen or antibody? What technique has been used in the detection of viral, fungal, and rickettsial antibodies? What test involves a two-stage process: (1) a test system with antigen and antibody, one of which is unknown, and (2) an indicator system consisting of sheep red blood cells coated with hemolysin, which will cause lysis of the indicator cells in the presence of complement If patient antibody is present, it will combine with the reagent antigen, and what will bind? If hemolysis is present in the complement fixation test, this means that no patient antibody was present, and the test is? Lack of hemolysis in the complement fixation test then the test result is? Which testing results are expressed as the highest dilution showing no hemolysis? Why is the use of controls is extremely important? What test uses the following controls for testing: running known positive and negative sera, an antigen control, a patient serum control, a cell control, and a complement control? Complement fixation testing Complement fixation testing complement negative positive Complement fixation testing to ensure the accuracy of test results Complement fixation testing 64
