I. Defense Mechanisms!A. Innate Immunity: mechanical barriers, phagocytic cells, complement, inflammation 1. Features: limited specificity, limited diversity, short lag time, no memory, nonreactive to self!2. epithelial, low pH, granulocytes, macrophages, lysozymes, blood proteins= complement, skin + mucous membranes!3. Blood protein complement --> inflammation, mast cell degranulation, chemotaxic agens, opsonins, bacterial lysis!B. Adaptive Immunity/lymphoid system: lymphocytes, antibodies!1. Features: Antigen specific, large diversity, long lag time (days), memory (acquired immunity), nonreactive to self!II. Adaptive Immunity/Lymphoid System!A. First step (nec, but not sufficient) in triggering an immune response= recognition of an antigen by surface receptors on lymphocytes!1. Antigens/immunogens= substances that can induce immune responses!2. Antigenic determinants/epitopes= small part of the antigen recog. and bound by lymphocyte's surface receptor. Antigens CAN have >1 epitope. !B. Primary lymphoid organs (bone marrow and thymus) = organs where lymphocytes develop and become immunocompetent. B cells do this in bone marrow, T cells in thymus.!1. Lymphocyte stem cells in the bone marrow and thymus divide w/o antigens= antigen-independent proliferation!2. Become immunocompetent= begin to express surface receptors --> division of these cells --> formation of clones and all clones recog. same antigen/epitope!C. Secondary lymph organs/tissues= sites where lymphocyter encounter foreign antigens and immune responses occur!1. Naive cells= never encountered a recognizable antigen!2. Clonal selection= foreign antigens activate a limited # of clones, surface receptors of clones recognize and bind antigen!3. Antigen-dependent proliferation: recog. and binding of antigen and other factors --> lymphocyte activation and rapid prolif. --> clonal expansion= # of lymphocytes in the clone increases!4. Lymph. --> effector cells (functionally active, short lived) !- B lymp. effector cells: plasma cells - T lymp. effector cells: cytotoxic T-lymphocytes (CTLs) and T helper cells !- continued presence of antigen REQUIRED for sustained viability of effector cells!- eliminating antigen --> effector cell apoptosis!5. Memory cells= functionally inactive, long-lived cells formed during immune response, cont. presence of antigen not req. for viability, they remain VIABLE after antigen is eliminated!D. Stages of immune response!1. Recognition phase: receptors on surface of lymphocytes bind to antigens!2. Activation phase: lymphocytes become activated and go thru clonal expansion!3. Effector phase: effector cells remove antigen from body!4. Decline/homeostasis: when antigen is elimated, effector cells --> apoptosis!5. Memory: surviving memory cells provide basis for acquired immunity E. Memory cells = source of acquired immunity 1. Upon 1st exposure to antigen (primary immune response) memory cells are created --> increasing the size of a clone!2. Upon subsequent exposures to antigen (secondary immune response), memory cells quickly differentiate into effector cells!3. Secondary immune response is greater in magnitude and happens quicker (decreased lag time) than primary immune response due to presence of memory cells created during that primary immune response!III. Lymphocytes and Accessory Cells!A. B lymphocytes carry out humoral (long distance) immunity!1. Effector cells of B lymph= plasma cells --> secrete antibodies into blood. Humoral immunity= long distance because plasma cells may be at a site far from infection!2. Structure of antibodies!- 2 indentical heavy chains and 2 identical light chains held together by disulfide bond. Can form dimers, tetramers, pentamers.!- Antigen binding site/active site: formed by highly variable N-termini of 1 heavy chain and 1 light chain, antibodies have 2 active sites!- Fc fragment: constant region of heavy chain, 5 isotypes of antibodies determined by Fc fragment!- Fab fragment: antigen binding fragment!- Isotype/class determined by C-termin. segment of heavy chains!3. Functions of antibodies!- Agglutination: formation of large antigen-antibody complexes!- Opsonization: antibodies coat surface of an antigen and mark it for disposal by macrophages and neutrophils!- Direct action/neutralization: antibody binding --> neutralization of viruses/bacteria/toxins!- Complement activation!- Induction of inflammation!4. 5 isotypes of antibodies based on C-terminal heavy chain sequence!- IgA: secretory antibody in tears, salivia, lumen of gut, nasal cavity, milk (passive immunity to baby), form dimers- IgD: B lymphcyte surface receptor --> trigger B cell activation - IgE: Fc region binds to receptors on mast cells, basophils, eosinophils--bound IgE+ antigen --> degranulation. Responsible for allergic rcns and imp. in defense against parasitic infections. - IgG: most abundant immunoglobin in blood and tissue, only Ig that cross placental barrier. Fc region binds to macrophages and neutrophils. - IgM: B lymphocyte surface receptor, forms pentamers in tissues/blood, activates complement!5. B lymphocytes are responsible for the destruction of bacteria and other exogenous foregin substances!- Surface receptors are membrane-bound IgM and IgD antibodies!- Recognize unprocessed antigen!- Process antigen + combine w/MHCII molecules to start activation of Th cells --> activated Th cells secrete cytokines --> active B cells --> stimulate their differentiation into plasma and memory cells!- B lymphocyte respons usually req. Th cells, some antigens can elicit a B cell response w/o presence of Th cells, but no memory cells are formed!- Antibodies secreted by effector plasma cells have same specificity for antigen as the surface antibodies of the B lymphocyte from which it arose !- As immune response proceeds these processes occur:!- Isotype switching: isotype of secreted antibody changes!- Affinity maturation: antibodies w/higher affinity for antigen are formed!B. T lymphocytes are responsible for cellular (short distance) immunity= effector T cells have to travel to site of infection!1. T lymp. are MHC restricted!- T lymphocytes only recog. antigen assoc. w/a MHC= major histocompatibility complex molecule on surface of an accessory cell - MHC molecules are integral membrane proteins on surface of most nucleated cells, play a critical role in transplant rejection!- 2 MHC classes: MHCI (present on most nucleated cells) and MHCII - MHCII only present on antigen presenting
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