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Chapter 43: The Immune System Essential Knowledge 2.d.2 - Homeostatic mechanisms reflect both common ancestry and divergence due to adaptation to different environments (43.3).  2.d.3 – Biological systems are affected by disruptions to their dynamic homeostasis (43.2-43.4).  2.d.4 – Plants and animals have a variety of chemical defenses against infections that affect dynamic homeostasis (43.1-43.4).  3.d.2 Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling (43.2).  Focus Topics Immunological responses to pathogens, toxins, and allergens  Vertebrate immune systems have nonspecific and nonheritable defense mechanisms against pathogens  The mammalian immune system includes two types of specific responses: cell mediated and humoral  In the cell-mediated response, cytotoxic T cells, a type of lymphocytic white blood cell, “target” intracellular pathogens when antigens are displayed on the outside of the cells.  Focus Topics In the humoral response, B cells, a type of lymphocytic white blood cell, produce antibodies against specific antigens.  Antigens are recognized by antibodies to the antigen.  Antibodies are proteins produced by B cells, and each antibody is specific to a particular antigen.  A second exposure to an antigen results in a more rapid and enhanced immune response.  Introduction to Immunity Defense system  Protects from bacteria, viruses, other pathogens, early-stage cancer cells  Three types of immunity:  1. Innate: nonspecific defense mechanisms  external physical barriers of skin mucous membranes  internal defenses of chemicals and phagocytic cells  Ex: gastric juices, histamines, inflammatory response Introduction to Immunity  Three types of immunity: 2. Acquired: adaptive immunity, line of defense in which lymphocytes react specifically to threat, two types  Humoral – antibodies produced by cells mark microbes for destruction, involves B cells  Cell-mediated – cytotoxic lymphocytes destroy infected body cells, cancer cells and foreign tissue, involves helper T cells 3. Passive: acquired temporarily ◦ Ex: through breast-feeding  Organs/Tissues/ Glands involved: ◦ ◦ ◦ ◦ ◦ ◦ Bone/bone marrow Spleen Stomach/Intestines Skin Lungs Lymph nodes Introduction to Immunity  Leukocytes are the cells which are the bulk of your immune system. ◦ Produced or stored in:  Thymus, spleen, and bone marrow (called the lymphoid organs)  There are also clumps of lymphoid tissue throughout the body (primarily as lymph nodes) that hold leukocytes Introduction to Immunity  The two basic types of leukocytes are: ◦ Phagocytes, cells that chew up invading organisms  Ex: neutrophils ◦ Lymphocytes, cells that allow the body to remember and recognize previous invaders and help the body destroy them  Ex: B and T cells Introduction to Immunity The leukocytes circulate through the body between the organs and nodes via lymphatic vessels and blood vessels.  In this way, the immune system works in a coordinated manner to monitor the body for germs or substances that might cause problems.  Innate Immunity  External defenses ◦ Skin – secretions lower pH (discourage microbial attack) ◦ Mucous membranes (line digestive, respiratory, genitourinary tracts)  Gastric juice – lowers pH to acidic  Epilethial lining of respiratory – traps microbes ◦ Lysozyme – enzyme that attacks bacterial cell walls  Present in tears, saliva, and mucus ◦ Serve as physical barriers to microbes Innate Immunity  Internal defenses ◦ Systemic response may include:  Increase in number of circulating WBCs  Fever  Triggered by toxins produced by pathogen or chemicals released by immune system  Stimulates phagocytosis and thus tissue repair and immune response  Inflammation  Redness, swelling, heat  Occurs when damaged mast cells (in connective tissue) release histamine  Histamine: triggers dilation and leakiness of blood vessels Innate Immunity  Internal defenses ◦ Relies upon phagocytosis by special WBCs (phagocytes)  These cells release antimicrobial proteins to help initiate an inflammation response  Rely upon cell surface rectors to bind to microbial surface receptors  Then, engulfs microbe and kill them using lysosome toxins  Neutrophils: most numerous phagocytic WBCs  Eosinophils: WBCs that attack multicellular parasites  Dendritic cells: stimulate acquired immunity Innate Immunity  Internal defenses ◦ Natural killer (NK) cells: nonphagocytic cells that also participate in innate defenses  Recognize general features of viral-infected or cancer cells  Attaches to them and triggers apoptosis ◦ Complement system: 30 proteins that can lyse microbes, trigger inflammation or assist in acquired immunity ◦ Interferons: stimulate neighboring cell to produce anti-viral reproduction substances Acquired Immunity  Introduction ◦ First visit: Immune System Preview ◦ Key cells: lymphocytes (WBCs) ◦ Activated by contact with microbes OR by cytokines (proteins secreted by macrophages) ◦ Recognizes antigens (foreign molecules)  Most are large proteins or polysaccharides  Often protrude from surface of microbe  Epitope: region of antigen to which lymphocyte attaches Acquired Immunity  Antigen Recognition ◦ Performed by B and T cells  B lymphocytes (B cells) and T lymphocytes (T cells) circulate in blood and lymph  Found in spleen and lymph nodes  Recognized by antibodies to the particular antigen  Both contain membrane-bound antigen receptors which allows them to recognize specific epitopes (where they will bind) Acquired Immunity  Antigen Recognition ◦ B cell receptor  Y-shaped  Consists of 4 polypeptide chains (two light chains and two heavy chains) ◦ T cell receptor  One alpha chain and one beta chain  Recognize special cell-surface proteins made by MHC (major histocompatibility complex – a family of genes) Acquired Immunity  Primary immune response ◦ Begins this response upon first exposure to an antigen (foreign molecule) ◦ Requires about 10-17 days to yield maximum response via T and B-cells ◦ Immunological memory: secondary immune response that provides long-term protection against a previously encountered pathogen  “To avoid illness, expose yourself to germs, enabling your immune system to develop antibodies. I don’t know why everyone doesn’t do this. Maybe they have something against living forever.” ~Dwight Schrute Acquired Immunity  Two types: ◦ Humoral immune response  Involves B cell activation and production of antibodies  Antibodies then circulate in blood and lymph  Provide defense against pathogens and toxins in the extracellular fluid ◦ Cell-mediated response  Involves cytotoxic T cells that destroy infected body cells, cancer cells and transplanted tissues  Relies upon Helper T cells to activate B cells and cytotoxic T cells Acquired Immunity   Only found in vertebrates T cells and B cells ◦ Types of WBCs called lymphocytes ◦ Originate from stem cells in the bone marrow ◦ Some lymphocytes migrate from the marrow to the thymus  These mature into T cells ◦ Some lymphocytes remain in the marrow  These develop into B cells ◦ Other lymphocytes stay in the blood and become the natural killer cells of innate immunity Acquired Immunity   Antigens are substances that prompt a response from a B or T cell Antigen receptor proteins allow B and T cells to bind to antigens ◦ Specific enough to bind to just one part of one molecule from a particular pathogen ◦ Millions of antigen receptors (AR) are produced, but all AR’s are identical on each B and T cell ◦ Up to 100,000 AR’s on the surface of each B and T cell! ◦ See Fig. 43.9, page 935 Antigen Specifics   Usually foreign Large molecules ◦ Proteins or polysaccharides    Protrude from the surface of foreign cells or viruses Some, such as bacterial toxins, are released into the extracellular fluid Small, accessible portion that binds to an AR is called an epitope or antigenic determinant ◦ Each antigen has several different epitopes, each binding a receptor with a different specificity B Cell and Antibody-Antigen Recognition  Each B cell AR is a Y-shaped molecule of 4 polypeptide chains ◦ Two identical heavy chains ◦ Two identical light chains ◦ Fig. 43.9, page 935  Light and heavy chains have a constant region where amino acid sequences don’t vary much and a variable region on which the amino acid sequence varies extensively from one B cell to another Formation of Antibodies  When a B cell AR binds to an antigen, that will elicit B cell activation eventually leading to the formation of cells that secrete a soluble form of the receptor ◦ The secreted protein is an antibody or immunoglobulin (Ig)  Antibodies are Y-shaped like the B cell AR’s ◦ But are secreted rather than membrane-bound ◦ Antibodies are the proteins that defend against pathogens ◦ Differences in amino acid sequences of variable regions on the B cell AR’s allow highly specific binding B cell AR’s and antibodies bind to intact antigens in the blood and lymph  Fig. 43.10, page 936  T Cell Antigen Recognition T cell AR’s are two different polypeptide chains, an α chain and a β chain, linked by a disulfide bridge (fig. 43.11, page 936)  Outer tips of each chain consist of the variable region and are where the antigen binds  Remainder of the molecule is the constant region  Bind to fragments of antigens that are presented on the surface of host cells  ◦ The host protein that displays the antigen fragment on the cell surface is the MHC (major histocompatibility complex) molecule Recognition of Protein Antigens by T Cells Begins when a pathogen or part of a pathogen either infects of is taken in by a host cell (Fig. 43.12, page 937)  Enzymes in the host cell break the antigen into smaller peptides called antigen fragments  ◦ These bind to MHC molecules inside the cell ◦ MHC molecule with the bound antigen fragment move to the cell surface resulting in antigen presentation  This advertises that the host cell contains a foreign substance  If the cell displaying an antigen fragment encounters a T cell that is the right match, the AR on the T cell will bind to the antigen fragment and the MHC molecule ◦ This binding is necessary for a T cell to participate in an adaptive immune response Acquired Immunity  Active immunity: acquired when body produces antibodies and develops immunological memory from either exposure to actual pathogen OR from immunization/vaccinization ◦ Vaccine can be:     1) inactive toxic 2) killed/weakened microbe 3) portion of microbe 3) genes for microbial proteins Passive Immunity  Passive immunity: temporary immunity provided by antibodies ◦ Supplied through:  Placenta to fetus  Milk to nursing infant  Antibody injection Tissue Transplant Limited by immune system’s ability to distinguish self from nonself  Immune system responds negatively to chemical markers (unlike itself) during blood transfusions (and tissue transplantation)  Mother and fetus: Rh factor  ◦ Rh: protein, RBCs antigen ◦ If fetal blood is different from mother, fetal blood can leak across placenta (creating immunological response from mother) Tissue Transplantation  Organ and Tissue Transplants ◦ May be rejected b/c the foreign MHC molecules are antigenic ◦ Triggers immune response ◦ Use closely related donors and immune system suppressor drugs to minimize risk of rejection Immune System Diseases  Allergies ◦ Hypersensitivity to certain environmental antigens (allergens) ◦ Releases histamines – creating inflammatory response that may include:  Sneezing  Runny nose  Difficulty breathing ◦ Antihistamine drugs – those that combat these symptoms by blocking histamine receptors ◦ Ex: Asthma, eczema (dry skin), environmental allergies (dust, dust mites, grass) Immune System Diseases  Autoimmune Disease ◦ Ex: Lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus, multiple sclerosis ◦ May be caused by failure in regulation of selfreactive lymphocytes ◦ Causes immune system to turn against itself ◦ Ex: Scleroderma, a chronic autoimmune disease that can lead to inflammation and damage of the skin, joints, and internal organs ◦ Ex: Ankylosing spondylitis, a disease that involves inflammation of the spine and joints, causing stiffness and pain Immune System Diseases  Immunodeficiency diseases ◦ Ex: AIDS (caused by HIV), cancer, Hodgkin’s disease, stress ◦ Suppress the immune system ◦ Become highly susceptible to opportunitistic infections (like pneumonia, flu, etc) ◦ Ex: DiGeorge syndrome (thymic dysplasia), a birth defect in which kids are born without a thymus gland ◦ Ex: Chediak-Higashi syndrome and chronic granulomatous disease both involve the inability of the neutrophils to function normally Exclusion Statements  Memorization of the structures of specific antibodies is beyond the scope of the course and the AP Exam.
 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
                                             
        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