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The Immune System • Defense mechanisms keep us healthy – Physical and chemical barriers i.e. skin, stomach acids • Prevent many harmful substances from entering body and kill many that successfully entered – Nonspecific mechanisms i.e. WBC which engulf harmful organisms (phagocytosis) • Help body to respond to tissue damage – Specific defense mechanisms i.e. immune responses • Recognize and kill particular microorganisms and abnormal cells Lec 9 & 10-Lymph & Immune HANDOUT 1 • mechanisms work simultaneously to protect us. – wide variety of cells, proteins, chemicals and organs are involved including lymphatic system, immune system, and circulatory system. • Some microorganisms cause cell death and disease. called pathogens. – invade or poison living cells. • Release enzymes or toxins that damage cells • cause cell rupture, or invade cells and use raw materials within cell to duplicate themselves and starve or kill healthy cell. Lec 9 & 10-Lymph & Immune HANDOUT 2 • Eukaryotes (most organisms except bacteria) – Defining feature of eukaryotic cells is membrane bound nucleus. • Nucleus contains chromosomes and associated proteins. • Have well organized internal structures called organelles. Lec 9 & 10-Lymph & Immune HANDOUT 3 • Prokaryotes (bacteria) – Single celled – No nucleus or membrane bound organelles – DNA contained in 1 chromosome – Outer surface covered by a rigid cell wall that surrounds the plasma membrane and gives bacteria their shape (spheres, rods, spiral) – Use of variety of resources to get materials for energy, growth and reproduction Lec 9 & 10-Lymph & Immune HANDOUT 4 Viruses • Extremely small infectious agents – Structurally, consists of only a small piece of RNA or DNA, which contains the virus’ genetic material, surrounded by a protein coat – Has no organelles of its own so can’t grow or reproduce on its own; forces living cell to make more copies of the virus. • Viruses can only reproduce when they make contact with a living cell. Take over living cell and use cell’s organelles to reproduce Lec 9 & 10-Lymph & Immune HANDOUT 5 • Modes of entry into living cells: – Taken into cell cytoplasm by endocytosis. Once inside, protein coat dissolves and viral genetic material is released and incorporated into cell’s genetic material – Merge their outer coat with cell membrane and release genetic contents into cell’s cytoplasm – Attach to outer surface of cell membrane and inject their genetic material into cell • Once inside the cell, the virus’ genetic material causes cell to begin producing copies of virus Lec 9 & 10-Lymph & Immune HANDOUT 6 Prions • infectious proteins that cause normal brain cell proteins to misfold and build more prions. – (Word “prion” comes from the first 2 letters of protein and last 3 letters of infection) – prions accumulate in brain cells until cells malfunction or stop working. Infected cells die and burst, releasing prions to infect other brain cells. • Gradual build up of prions causes debilitating neurological symptoms and progressive degeneration. • No known cure available; prions resist cooking, freezing, drying • Disease called Mad Cow disease in animals or Creutzfeldt-Jakob disease in humans. Both fatal neurological disorders. Lec 9 & 10-Lymph & Immune HANDOUT 7 Determination of Health Risk Factors Which Determine the Danger from a Pathogen • Transmissibility: how easily it is passed from person to person • Mode of transmission: how it is transmitted – respiratory, fecal, oral, body fluids • Virulence: how damaging the resulting disease is Lec 9 & 10-Lymph & Immune HANDOUT 8 lymphatic system movie • http://daphne.palomar.edu/ccarpenter/ scroll down to “useful and interesting anatomy-related links and about ¾ way down is link Lec 9 & 10-Lymph & Immune HANDOUT 9 Lymphatic System The lymphatic system consists of : • Lymphatic vessels • Lymphoid tissues and organs throughout the body – Lymphatic vessels transport back to the blood any fluids which have escaped from the circulatory system and moved into the interstitial fluid. • Once interstitial fluid enters a lymphatic vessel, its name changes to lymph – Lymphatic tissues contain phagocytic cells and lymphocytes which are essential to the body’s defense mechanism and its resistance to diseases. • Lymph nodes-clean lymph as it passes through them Lec 9 & 10-Lymph & Immune HANDOUT 10 Lymphatic System Functions: —Protection against disease and injury —Filtration of foreign material to defend against infection and injury —Maintenance of blood volume in cardiovascular system —Capillaries are not watertight and some fluid leaks out into the tissues —Removes excess tissue fluid & returns it to the circulatory system —Transport of fats and fat-soluble material absorbed from the digestive system —Lymph activates the immune system. —Lymphocytes monitor the lymphatic stream for the presence of antigens and mount an attack against them. Lec 9 & 10-Lymph & Immune HANDOUT 11 Lymph: WBCs, fat cells, and protein-containing fluid transported by lymphatic vessels; Lymphatic vessels have: – Walls consisting of 3 thin layers – One way valves to prevent backflow of lymph (lymph flows only toward the heart) – Skeletal muscle contraction and pressure changes in the chest during breathing keep the lymph flowing Lec 9 & 10-Lymph & Immune HANDOUT 12 – Lymph capillaries have wide spaces between its cells. • Can take up substances, including proteins, bacteria and cancer cells, that are too large to enter a blood capillary. • These substances use the lymphatic vessels to travel throughout the body. – Lymphatic capillaries are typically located throughout the blood capillary beds • Easy to pick up the fluid that has leaked from the circulatory system into the tissue spaces. Lec 9 & 10-Lymph & Immune HANDOUT 13 – As blood circulates through the body, nutrients, wastes and gasses are exchanged between the blood and the interstitial fluid. – Fluid which remains in the tissue spaces becomes part of the interstitial fluid (approximately 3 liters). – This fluid and any plasma proteins that escape from the blood stream are carried back to the blood. – As the fluid pressure in the tissue spaces increases, little flaps in the lymphatic capillaries are forced open, the excess fluid enters the lymphatic capillaries and is returned into the circulatory system • Ensures that there is sufficient blood volume for circulatory system to function properly. Lec 9 & 10-Lymph & Immune HANDOUT 14 Located at intervals along the lymphatic vessels are organs called lymph nodes. • Lymph nodes are the principal lymphatic organ in the body. – Nodes filter and remove microorganisms, cellular debris, and abnormal cells from the lymph before returning the cleansed fluid to the cardiovascular system. – This prevents microorganisms from being spread into the blood and sent to other parts of the body • Lymph nodes cluster along the lymphatic vessels and most are buried in connective tissue so we can’t see them. • Large clusters of nodes occur near body surfaces in the inguinal (groin), axillary and cervical regions. Lec 9 & 10-Lymph & Immune HANDOUT 15 • Lymphatic capillaries merge to form small vessels larger and larger vessels trunks 2 major lymphatic ducts – the right lymphatic duct and the thoracic duct – right lymphatic duct drains the right arm and the right side of the head and chest and drains into the right subclavian vein; -- thoracic duct is larger and drains lymph from rest of the body and drains into left subclavian vein Lec 9 & 10-Lymph & Immune HANDOUT 16 Other important lymphatic system structures: – Spleen, thymus gland, tonsils and adenoids Spleen---Largest lymphatic organ • Is a site for production of lymphocytes, usually in response to invading pathogens, and RBC • Contains macrophages that – filter blood and trap bloodborne antigens; – scavenge and break down microorganisms, foreign matter, and old or damaged RBC and platelets – Saves hemoglobin (iron) from the RBC Lec 9 & 10-Lymph & Immune HANDOUT 17 Spleen: • Cleans and stores blood; – blood is used in case of severe blood loss (hemorrhage) or a fall in blood pressure or whenever extra oxygen carrying capacity is needed. • Immune surveillance and response • Helps fight infection Lec 9 & 10-Lymph & Immune HANDOUT 18 • If the spleen is removed, the lymph glands, liver and bone marrow take over most of its functions. – In children under 12, the spleen can regenerate if a small part of it is left in the body • Main distinction between spleen and lymph nodes is which fluid they clean – Spleen cleans the blood – Lymph nodes clean the lymph • Together they keep the circulating body fluids clean of damaged cells and microorganisms. Lec 9 & 10-Lymph & Immune HANDOUT 19 Some Diseases Can Cause Spleen to Enlarge: • an enlarged spleen more likely to rupture and bleed if injured – Tuberculosis, Mononucleosis, leukemia • A swollen spleen can be felt as a lump in upper left abdomen • A strong blow to abdomen can rupture spleen and cause severe internal bleeding. – splenectomy to prevent hemorrhage – can live without a spleen because functions are shared by lymph glands, liver, red bone marrow – are more vulnerable to infection if have had splenectomy Lec 9 & 10-Lymph & Immune HANDOUT 20 Thymus • Gland contains lymphocytes and epithelial cells • Secretes 2 hormones, thymosin and thymopoietin, that stimulate T lymphocytes (T cells) to mature and work against specific pathogens which invade body • Gland is largest and most active during childhood and begins to shrink after adolescence since defense mechanisms are usually well established by then. Lec 9 & 10-Lymph & Immune HANDOUT 21 Tonsils • Lymphocytes in tonsils gather and filter out many of the microorganisms that enter throat in food or air • Tonsillitis and tonsillectomy: – Tonsils in the back of the throat are largest and most often infected – If infection is serious, tonsillectomy Lec 9 & 10-Lymph & Immune HANDOUT 22 Adenoids • Also known as pharyngeal tonsils; are at back of nasal passages • Tend to enlarge during early childhood, begin to shrink after 5 years of age, and disappear by puberty • If keep enlarging and block airflow from nose to the throat – Causes mouth breathing, a nasal voice, and snoring – Remove surgicallyadenoidectomy Lec 9 & 10-Lymph & Immune HANDOUT 23 Lines of Defense The lymphatic system works with other body systems to protect us against pathogens and cellular changes Remember the defense mechanisms which we spoke about earlier: – Physical and chemical barriers – Non-specific defense mechanisms – Specific defense mechanisms Lec 9 & 10-Lymph & Immune HANDOUT 24 Non-Specific Defense Systems First Line of Defense • Physical and chemical barriers – Physical barriers: prevent pathogens from entering the body – Chemical defenses produce substances that slow the growth or kill pathogens • The intact skin and mucous membranes are our most important barrier and first line of defense. • Structure: dead layer, inhospitable to microorganisms • Constant replacement and repair: many adhering microorganisms removed • Acidic pH (5–6): too acidic for many microorganisms; this inhibits their growth • Sweat glands produce antibiotic fluid (dermicidin) Lec 9 & 10-Lymph & Immune HANDOUT 25 • Other: tears, saliva (saliva and tears secrete lysozyme, an enzyme which kills bacteria), earwax, digestive acids, hair, mucus (mucus is sticky and traps pathogens), vomiting, urination, defecation, resident bacteria (normal flora), mucous membranes (line all body cavities open to the exterior) • Most “successful” pathogens enter the body where we don’t have skin and they can take advantage of moist surfaces in direct contact with living cells. Lec 9 & 10-Lymph & Immune HANDOUT 26 Nonspecific Defenses: Second Line Antimicrobial proteins, phagocytes and other cells inhibit the spread of invaders throughout the body. – These defenses don’t target specific pathogens; they occur in response to any body threat • They work to actively seek out pathogens which have penetrated our physical and chemical barriers and are killing or damaging cells and then attack the invaders – Respond to tissue damage by removing debris Lec 9 & 10-Lymph & Immune HANDOUT 27 Nonspecific Defenses Phagocytosis: by neutrophils, macrophages (chief phagocyte), and eosinophils • Neutrophils (most abundant WBC) are the first WBC at the infection site. – Antimicrobial chemicals (defensins) are produced and pierce the pathogen’s cell membrane – They engulf, digest and destroy bacteria in the blood and tissue fluids • Remember that some WBC can filter through the walls of blood vessels into tissue spaces (they are attracted by substances released by injured cells at the infection site) Lec 9 & 10-Lymph & Immune HANDOUT 28 – Monocytes leave the blood vessels, enter the tissue fluids, and develop into macrophages which engulf and digest large numbers of pathogens and anything foreign to the body and help to activate T cells. • Macrophages also cleanup by scavenging old blood cells, dead tissue fragments and other cellular debris. – They also release chemicals that stimulate the production of more WBC. – Eosinophils surround large invaders and bombard them with digestive enzymes as well as surround and digest some foreign proteins. Lec 9 & 10-Lymph & Immune HANDOUT 29 • When the body is actively fighting an infection, many WBC die. • We also have tissue fluid, dead phagocytes, dead pathogens and cellular debris at the infection site. – These produce pus. • If the pus becomes trapped and can’t drain, body forms an abscess. – walls off pus by forming a connective tissue “jail cell” Lec 9 & 10-Lymph & Immune HANDOUT 30 Inflammatory response / Inflammation: • Triggered by any type of tissue injury – Ultimate goal of inflammation is to clear the injured area of pathogens, dead tissue cells, and other debris so that the tissue can be repaired • Visible Signs: redness, warmth, swelling, pain, and sometimes, impairment of function – we rest the injured part to decrease the flow of inflammatory material from the injured area – Tissue damage leads to release of chemicals from damaged cells. The chemicals stimulate MAST CELLS, connective tissue cells specialized to release histamine. Histamine causes blood vessels to dilate so more blood flows into the area which causes the redness, warmth/heat, swelling. Lec 9 & 10-Lymph & Immune HANDOUT 31 – Local capillaries also release fluid containing clotting factors and antibodies. This fluid goes into the tissue spaces, causing swelling and then pain from pressure on local nerve endings. • Swelling helps to dilute harmful substances and brings complement proteins and clotting factors. • Complement system or complement proteins – Group of plasma proteins that circulate, in an inactive state, in the blood and assist other defense mechanisms; they enhance or “complement” the effectiveness of all the lines of defense – When presence of an infection activates a complement protein, the protein activates another and each protein keeps activating others. Lec 9 & 10-Lymph & Immune HANDOUT 32 Some complement protein cells: – form large protein complexes that create holes in (lyse) bacterial cell walls. • Fluids and salts enter and the bacterium swells and bursts. (Normal cells have proteins to inactivate the complement.) – bind to bacterial cell membranes and mark them for destruction by phagocytes. – stimulate mast cells to release histamine or help get additional phagocytes to infection site. – dispose of cellular debris – begin tissue repair process Lec 9 & 10-Lymph & Immune HANDOUT 33 Second Line of Defense Natural killer (NK) cells: lymphocytes which destroy tumor cells and virus infected cells by releasing chemicals that break down their targets’ cell membranes. – (NK cells are non-specific killers; they do NOT target specific enemies). – They police the body via the blood and lymph and identify invading cells by markers on the plasma membranes (the lack of “self” cell surface receptors). – After an attack from NK cells, the “bad” cell membranes develop holes and the nucleus disintegrates. – NK cells also secrete substances that help the inflammatory response. Lec 9 & 10-Lymph & Immune HANDOUT 34 • Interferons: interfere with virus spread – When a cell becomes virus infected, it will ultimately succumb to the virus, but it will try to help protect other normal cells by releasing a group of proteins called interferons. • Viruses lack the cellular machinery to make ATP or proteins. In order to survive, the viruses alter the host’s cell’s “machinery” so it will make more viruses. – Interferons diffuse to healthy cells, bind to their cell membranes, and stimulate the still healthy cell to produce proteins that prevent the virus from making the proteins it needs to survive. This makes it harder for the virus to establish itself. • Interferons also activate macrophages and mobilize natural killer cells. Lec 9 & 10-Lymph & Immune HANDOUT 35 • Video on viruses • http://www.npr.org/blogs/krulwich/2011/06/ 01/114075029/flu-attack-how-a-virusinvades-your-body Lec 9 & 10-Lymph & Immune HANDOUT 36 • Fever: increases host cell defenses and metabolic activity – When macrophages attack they release pyrogens into the bloodstream and cause a fever – The higher temperature helps our body fight infection and makes the virus uncomfortable due to the heat. • Fever increases the metabolic rate and thus speeds up the defense mechanisms and tissue repair processes • An extremely high fever can be dangerous because it can affect the shape of the chemical bonds that give proteins their shape and allow them to function. • Inflammation is localized response to infection; fever is systemic response to invading microorganisms Lec 9 & 10-Lymph & Immune HANDOUT 37 immune response: • http://www.cancerresearch.org/Resources.aspx?id=586 • http://highered.mcgrawhill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites /dl/free/0072437316/120110/micro33.swf::Interaction of Antigen Presenting Cells and T-helper Cells Lec 9 & 10-Lymph & Immune HANDOUT 38 Third Line: Specific Defense Mechanisms • Immune response—targets specific enemies, • takes more time to mobilize than non-specific defenses – Has 3 important characteristics: • Recognizes and targets specific pathogens or foreign substances • Has “memory”—stores information from past exposures so responds more quickly next time pathogen attacks • Is systemic; protects entire body (resulting immunity is not limited to infection site) Lec 9 & 10-Lymph & Immune HANDOUT 39 • Key to this specific defense is the body’s ability to distinguish between self and non-self. – Defends the body by directly attacking cells – indirectly by releasing mobilizing chemicals and protective antibodies (proteins that bind with and neutralize specific antigens) – Genes determine which foreign substances our immune system will be able to recognize and resist Lec 9 & 10-Lymph & Immune HANDOUT 40 Has 2 separate but overlapping branches 1. Humoral immunity: provided by antibodies present in the body’s “humors” or fluids—blood, lymph --antibodies (produced by B lymphocytes) circulate in the blood and lymph and bind to bacteria, bacterial toxins, and free viruses. They inactivate these microorganisms and mark them for destruction by phagocytes or complement. 2. Cell mediated immunity: T lymphocytes and other cells protect the body and defend it attacking the infected cells. – act directly to kill the foreign cells or – indirectly release chemical mediators that stimulate the inflammatory response or activate other lymphocytes or macrophages Lec 9 & 10-Lymph & Immune HANDOUT 41 • Antigens (antibody generating) • Any substance that mobilizes immune system and causes an immune response. • Each antigen has a unique shape so immune system can recognize it. –Antigens are usually a large protein or polysaccharide molecule –The immune system responds by making antibodies to attack and kill antigen. Lec 9 & 10-Lymph & Immune HANDOUT 42 Major histocompatibility complex (MHC) proteins – self-markers or self-antigens--surface protein which our immune system uses to recognize that cells belong to you. – They signal immune system to not react • Some small molecules don’t cause an immune response, however if they link up with body’s proteins, immune system may think they are foreign and start an attack, causing hypersensitivities i.e. allergies, medicine reactions, poison ivy reaction, etc.--AUTOIMMUNE • Transplant reactions Lec 9 & 10-Lymph & Immune HANDOUT 43 • Lymphocytes are the main fighter of the immune system and protect the body against antigens. • They come from the red bone marrow and mature into immunocompetent cells, either T cells (T lymphocytes) or B cells (B lymphocytes). • They are named for where they mature – T cells mature in the thymus gland; B cells mature in bone marrow – Both recognize and target antigen bearing cells differently. Activated T cells manage the immune response and some of them directly attack and destroy infected cells . B cells produce plasma cells which secrete antibodies into the blood and body fluids. Lec 9 & 10-Lymph & Immune HANDOUT 44 The immune system’s response depends on – the ability of its cells to recognize antigens, – bind to them – communicate with one another so that the whole system mounts a response specific to the antigens. Lec 9 & 10-Lymph & Immune HANDOUT 45 B cells are responsible for antibody-mediated immunity. • Antibodies are proteins that bind with and neutralize specific antigens. – are released into the lymph, blood, and tissue fluid so they can circulate throughout the body. – Antibodies immobilize antigens until they can be destroyed by phagocytes or other means. • B cells mature in bone marrow. –Mature cells have surface receptors that allow them to recognize specific antigens. – travel in the blood to the lymph nodes, spleen and tonsils and remain inactive until they meet a foreign cell with the specific antigen to which they respond. Lec 9 & 10-Lymph & Immune HANDOUT 46 • The foreign cell stimulates the B cell to grow and multiply. The resulting group of identical cells is called a clone. • Clone cells are also called plasma cells; they secrete their antibodies into the lymph and the blood plasma. (Plasma cells live for 4-5 days.) • Antibodies also produced by the B cells and circulate in our blood. – When the antibodies meets the correct antigen, they bind to them and create an antigen-antibody complex. – This complex marks the antigen and the cell carrying it for destruction. • Macrophages and activated B cells engulf foreign particles and digest them. Lec 9 & 10-Lymph & Immune HANDOUT 47 • Some of the clone cells become memory cells. – remain inactive in our body until the same antigen reappears. – Memory cells store information about the pathogen; • if we have a second exposure, the immune response is faster because the memory cells react immediately. Lec 9 & 10-Lymph & Immune HANDOUT 48 Antibodies: – Neutralize non-self antigens by inactivating them and tagging them for destruction – Their “Y” shape allows them to “lock” into a cell and attack its contents. – Five classes of antibodies: IgG, IgM, IgA, IgD, IgE Lec 9 & 10-Lymph & Immune HANDOUT 49 Immunoglobulins Antibodies are also called immunoglobulins; – are the gamma globulin part of blood proteins. – are proteins secreted by activated B cells or plasma cells in response to an antigen and bind specifically with an antigen. – Will latch onto intact bacteria and foreign molecules in the extracellular environment (body secretions, tissue fluid), as well as in blood and lymph. Five major classes: (MADGE is a mneumonic) • IgG-75% • IgM-5-10% • IgA-15% • IgD-<1% • IgE-0.1% Lec 9 & 10-Lymph & Immune HANDOUT 50 T cells • Circulate continuously throughout the body • responsible for cell-mediated immunity which depends upon the actions of several types of T cells. (They attack pathogens which enter into the healthy cell and damage it.) – T cells don’t produce antibodies; they directly attack foreign cells that carry antigens or they release proteins that boost other aspects of the immune response. – T cells can identify and kill infected human cells before the cells have a chance to release new pathogens into the blood. Lec 9 & 10-Lymph & Immune HANDOUT 51 – T cells are “designed” for cell to cell interactions and most of their attacks on antigens target body cells infected by viruses and bacteria, abnormal or cancerous body cells and cells of transplanted foreign tissues. – More T cells are mobilized when macrophages and activated B cells act as antigen-presenting cells (APCs) which engulf foreign particles, partially digest them and display fragments of the antigen on their surface. • serves as an alarm to other immune cells that there is invader in body. Lec 9 & 10-Lymph & Immune HANDOUT 52 Types of T Cells • Helper T cells (CD4 cell) : secrete a class of signaling molecules called cytokines which help recruit other immune cells to fight off intruders. – Lymphokines**, a protein that enhances inflammation and the immune response by stimulating the actions of T cells and macrophages – Interleukins** promote development of other immune cells. – Without helper T cells, there will be no immune response because they direct or help complete the activation of all other immune cells. – Are actually hormones Lec 9 & 10-Lymph & Immune HANDOUT 53 • Cytotoxic T cells (also known as Killer T cells) are the only cells that directly attack and kill abnormal and foreign cells. • Memory T cells: reactivate on re-exposure and stimulate the immune response. • Suppressor or Regulatory T cells suppress other immune cells after an antigen has been neutralized. - prevent the immune response from going haywire and attacking healthy cells. --may also help to control autoimmune reactions As infection is brought under control, regulatory T cells instruct the B cells, helper T cells, and killer T cells to switch to “stand-by”; • infection is winding down, they are not needed now Lec 9 & 10-Lymph & Immune HANDOUT 54 Immune Memory allows us to have immunity: Development of Immunity: Primary Immune Response • The first exposure to an antigen generates a primary immune response. • This process involves recognition of the antigen and production of B and T cells • Characteristics: lag time of 3–6 days for antibody production. – Antibody concentrations rise and peak at 10–12 days and then level off. • During lag time, B cells specific to the antigen multiply and develop into plasma cells. Lec 9 & 10-Lymph & Immune HANDOUT 55 Secondary Immune Response • B and T cells create a population of memory cells which is the basis for immunity from disease. • Subsequent exposure to the pathogen creates the secondary immune response. – This response is faster, longer lasting and more effective than the primary immune response. – Antibody levels remain much higher in the body after a second exposure to the same antigen. Lec 9 & 10-Lymph & Immune HANDOUT 56 Memory cells recognize the pathogen, bind to it, and produce T cells and plasma cells. • within a few days antibody concentrations rise rapidly. – Memory cells live for a long time and many retain their ability to generate a secondary immune response over a lifetime. – Other memory cells need to be reactivated by “booster” shots after a certain time period. Lec 9 & 10-Lymph & Immune HANDOUT 57 War Against Pathogens • Active immunization and vaccines: give body dose of antigen in advance so immune system will create primary immune response. If we are re-exposed to antigen, we have already developed antibodies and memory cells so body can react quickly. Are effective against viruses. • Passive immunization involves giving prepared antibodies (gamma globulin serum) for specific pathogen. Effective against existing infections; can be given if already exposed. – Provides short term immunity (2-3 weeks which is lifespan of prepared antibodies) because person’s own B cells aren’t activated and memory cells don’t develop. Lec 9 & 10-Lymph & Immune HANDOUT 58 • Antibiotics: kill bacteria or inhibit growth; effective only against bacteria (ineffective with viruses); resistance a problem • Monoclonal antibodies are produced in lab from clones of hybrid cells; are pure preparations of antibodies specific to one antigen – Typically used for screening tests i.e. pregnancy tests, STDs, cancer, hepatitis and rabies Lec 9 & 10-Lymph & Immune HANDOUT 59 Tissue Rejection Goal of the immune system is to protect the body from invasion by foreign cells. If tissue is not a match the body will reject it. • Transplants: 75% match essential – Before transplant can be done, need match between • ABO and other blood group antigens • Tissue match for MHC antigens – After transplant, patient must take immunosuppressive drugs to block any potential immune response • this can cause the person’s immune system to be unable to protect the body against any foreign agents and can cause death. Lec 9 & 10-Lymph & Immune HANDOUT 60 Recent advances in transplant surgery have made the outcome more successful: 1. improvements in immunosuppressive drugs, 2. better techniques for tissue typing, 3. national sharing of information and donor organs through organ bank systems Lec 9 & 10-Lymph & Immune HANDOUT 61 Inappropriate Immune Responses • An allergy is an inappropriate response of the immune system to an allergen (a substance that causes an allergic reaction). – hypersensitivity reaction; excessive inflammatory response. The immune system causes tissue damage as it fights off a perceived threat (pollen, animal dander) that would otherwise be harmless. – Localized: affect only the area exposed—warmth, swelling and pain; also increases secretion of mucus – Systemic: affect several organ systems; includes constriction of smooth muscle in the lungs and digestive system and dilation of blood vessels Lec 9 & 10-Lymph & Immune HANDOUT 62 • Anaphylactic shock: severe systemic allergic reaction. The allergen somehow enters the blood and circulates rapidly throughout the body. – Symptoms: difficulty breathing, severe stomach cramps, swelling throughout the body, circulatory collapse, life threatening fall in blood pressure – People with a history of strong allergic reactions need to carry a prescription emergency kit with an epinephrine filled syringe Lec 9 & 10-Lymph & Immune HANDOUT 63 Inappropriate Immune Responses: Autoimmune Disorders • Defective recognition of “self”the immune system produces antibodies and cytotoxic T cells that attack its own cells. – Possible causes: 1. certain antigens are never exposed to the immune system as it undergoes fetal development. These antigens were never programmed into the system as self so when tissue damage exposes them, the mature system responds as if they were foreign Lec 9 & 10-Lymph & Immune HANDOUT 64 To avoid potential auto-immune diseases, developing T cells are exposed to as many selfproteins as possible and the body will destroy any cells that display any reactivity to the body. This ensures that the remaining T cells will react only to non-self molecules. 2. Antibodies produced against a foreign antigen cross react with the person’s own tissues There are currently no cures for these disorders. Lec 9 & 10-Lymph & Immune HANDOUT 65 Some Autoimmune conditions: • Multiple Sclerosis- a disorder of the CNS which causes damage to the myelin sheath, so nerve impulses are slowed down or stopped. • Diabetes Mellitis • Glomerulonephritis: severe decrease in kidney function • Systemic Lupus erythematosus (SLE or lupus): body attacks its own connective tissue with inflammation and subsequent pain • Rheumatoid arthritis: inflammed synovial membrane which causes damage to the joints, tissues, and bones; B cells produce antibodies against a protein in the cartilage of synovial joints. • Myasthenia Gravis: impairs communication between nerves and skeletal muscles – Drooping upper eyelids, difficulty swallowing and talking and generalized muscle weakness Lec 9 & 10-Lymph & Immune HANDOUT 66 Immune Deficiency: general term for an improperly functioning immune system • AIDS (acquired immune deficiency syndrome) (Syndrome is a term for a group of symptoms that occur together) • Characterized by severe weight loss, night sweats, swollen lymph nodes, frequent infections • Disease Progression: – You become infected with HIV-the human immunodeficiency virus – HIV targets cells and attaches to CD4 receptors of T helper cells. It infects by entering the cell and using the cell’s machinery to reproduce itself Lec 9 & 10-Lymph & Immune HANDOUT 67 • Belongs to a class of virus called Retrovirus. This virus attaches to the CD4 receptor of a helper T cell. – fuses the retrovirus with the cell’s membrane and releases the viral RNA and enzymes into the cell. – forces the host cell to make viral DNA which is then inserted into cell’s DNA. – Now cell makes more of viral RNA and its proteins. Because T cell produces so many new viral cells, it uses up its energy, cell ruptures and releases more viral copies. Lec 9 & 10-Lymph & Immune HANDOUT 68 • Transmission: This is a fragile virus that can’t survive dry conditions. It cannot be transmitted by air, casual contact, doorknobs or toilet seats. – It can be transmitted in body fluids (i.e. blood, sexual contact, semen, breast milk, vaginal secretions), or contaminated hypodermic needles; pregnant mothers can pass it on to the fetus or the newborn. – It is not known to be transmitted by contact with urine, feces, saliva**, perspiration, tears** or nasal secretions. **=possibly transmitted here – Generally not transmitted blood transfusions now because of more extensive screening of donated blood. Lec 9 & 10-Lymph & Immune HANDOUT 69 • AIDS progression falls into 3 phases: – Phase I: lasts from a few weeks to a few years after initial exposure • flu-like symptoms: swollen lymph nodes, chills, fever, fatigue, body aches. • Virus is multiplying, antibodies are made but are ineffective for complete virus removal because virus particles remain inside the cells so antibodies can’t reach them. • Person is said to be HIV+; does not yet have AIDS Lec 9 & 10-Lymph & Immune HANDOUT 70 – Phase II: from six months to 10 years after initial exposure (generally it takes about 10 years to progress to this phase) • opportunistic infections generally present because more of the helper T cells are killed. 5% may not progress to next phase – In Phase I and II infected people may be unaware that they have HIV and can unsuspectingly pass it on to other people. – Phase III: helper T cells below 200 cells/mm, opportunistic infections and cancers present, now person is said to have clinical AIDS; untreated AIDS is nearly always fatal. Lec 9 & 10-Lymph & Immune HANDOUT 71 • By destroying so many of the helper T cells, the AIDS virus prevents our B cells from becoming activated to produce antibodies. This is why people with AIDS die of infections or cancers a healthy immune system can combat. AIDS Pandemic • More than 36 million infected with HIV worldwide • Most infections in sub-Saharan Africa • Increasing spread in Asia and India • Most often spread by heterosexual contact outside United States Lec 9 & 10-Lymph & Immune HANDOUT 72 New AIDS Treatments • Enzyme inhibitors: AZT, ddI, d4T, 3TC (inhibit enzymes virus needs in order to reproduce) • Protease inhibitors: ritonavir, saquinavir (protease is a required enzyme for viral protein assembly) • Early treatment may delay or prevent clinical AIDS • Vaccine: virus mutates rapidly preventing effective vaccine production at this time • The reason AIDS is so devastating is that the virus that causes AIDS destroys helper T cells and weakens the body’s ability to mount a cell mediated immune response. Lec 9 & 10-Lymph & Immune HANDOUT 73 Safer Sex • Abstinence • Reduce number of sexual partners • Choose sexual partners with low-risk behavior • Avoid high-risk sexual practices • Use latex or polyurethane condoms or barriers • GET TESTED Lec 9 & 10-Lymph & Immune HANDOUT 74