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PSL201Y1 (46)
Yue Li (10)


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Yue Li

23 THE IMMUNE SYSTEM SPECIFIC DEFENSES: IMMUNE RESPONSE  B lymphocytes develop into plasma cells that secrete antibodies, the actions of which bring about humoral immunity, so called because antibodies circulate in the blood and lymph, body fluids long ago called humors.  T lymphocytes develop into active cytotoxic T cells, which bind to and kill abnormal body cells (cell-mediated immunity); cytotoxic T cells must come into direct contact with their targets to act on them.  The circulating antibodies of the humoral responses defend against bacteria, toxins, and viruses.  T cells of the cell-mediated response are against bacteria and viruses that are hidden within infected body cells.  SPECIFICITY o B cells and T cells bind and respond to foreign or abnormal molecules known as antigens. o Antigens: complex protein or polysaccharide components of viruses, bacteria, fungi, protozoa, parasitic worms, pollen, transplanted tissue, and tumor cells. o Epitopes: antigenic determinants; recognition sites detected by specific lymphocytes, which then target that invader for destruction. o B cells and T cells are able to recognize specific antigens because they possess antigen-binding proteins (antigen receptors). Similar to receptors on antibodies. o A typical antibody is a Y-shaped molecule consisting of 4 protein chains: 2 identical heavy chains and 2 identical light chains joined by disulfide bridges. o Each antibody molecule posses variable regions (V) and constant regions (C). o Constant regions consist of portions of the heavy and light chains that make up the tail. o The variable regions of an antibody have amino acid sequences that vary extensively from antibody to antibody, consisting of portions of heavy and light chains making the top of the Y. o The 2 identical variable regions form 2 identical antigen-binding sites. Each antibody can bind 2 epitopes of the same kind. o The enzyme (antibody) and its substrate (antigen) show specificity. o B cell antigen receptors are often called membrane antibodies or membrane immunoglobulins. o Antigen receptors on T cells (T cell receptors, TCR) come from the same family of proteins that includes antibodies but are different in structure.  DIVERSITY o A single T lymphocyte or B lymphocyte has about 100 000 antigen receptors, all with the same specificity. o The particular antigen receptor molecules a given lymphocyte produces are determined by random genetic events that occur early in the development of the lymphocyte, hence specificity. o When a particular microorganism invades the body, it interacts with and activates only those lymphocytes that have receptors specific for antigens it possesses. o The foreign antigen triggers an immune response against itself. This antigen driven activation of lymphocytes is called clonal selection. o Lymphocyte differentiation rise to 2 populations: 1) effector cells which are short-lived cells that combat the same antigen that stimulated their production 2) memory cells which are long-lived cells bearing membrane receptors specific for the same antigen.  MEMORY o The antigen-induced lymphocyte changes that occur when a person is first exposed to an antigen constitute a primary immune response. o Primary immune response Antigen selected B cells and T cells proliferate and differentiate into effector cells (antibody-producing plasma cells and cytotoxic T cells, respectively) about 10-17 days after exposure to the antigen. o Acquired immunity is based on subsequent exposures to the same antigen, the response called secondary immune response. It is much faster (2-7 days) greater in magnitude, and more prolonged than a primary response. o Secondary immune response give rises to effector cells and clones of long-lived memory T cells and memory B cells.  SELF-TOLERANCE o B cells and T cells mature in the bone marrow and thymus. Their antigen receptors are in effect tested for their potential to recognize and react against self. o Those lymphocytes with receptors that reach with self-molecules are nonfunctional or undergo apoptosis (programmed cell death). Only reactive to foreign molecules. 23 THE IMMUNE SYSTEM Humoral Immunity THE ROLE OF B LYMPHOCYTES IN ANTIBODY PRODUCTION  When B cells binds with an antigen, it responds in 2 ways: 1. Stimulated to proliferate, which increases the number of B cells with the same specificity. 2. The cells differentiate, some become long-lived memory B cells and others become short-lived antibody- synthesizing effector cells called plasma cells.  Plasma cells secrete about 200-antibody molecules/sec over its life span of 4-7 days. They circulate throughout the blood and lymph for several weeks, binding to the same antigens that stimulated their production, thereby marking them for destruction by phagocytosis or complement-mediated lysis.  T-dependent antigens: antigens that evoke the production of both plasma cells and memory B cells. Do so with the help from a special kind of T cell (helper T cell).  Helper T cells secrete many cytokines (interleukin-2, IL-2). IL-2 and T-dependent antigens induce the proliferation of B cells.  Polysaccharide antigens can activate B cells without T cell help (T-independent antigens).  The polysaccharide bind many antigen receptors on the B cell surface, providing a strong enough stimulus to induce the B cell to proliferate even in the absence of IL-2. Without IL-2 there will be no memory B cells, only antibody-secreting plasma cells, hence no immunological memory.  B cell response to T-independent antigens takes longer, and the quantity is smaller than a secondary response. ANTIBODY FUNCTION IN HUMORAL IMMUNITY  Antibody has 2 functions: 1) binds specifically to an antigen (use antigen-binding sites) 2) aids in the inactivation or disposal of that antigen (tail of the Y shaped)  5 types: IgG, IgM, IgA, IgE, IgD (Ig = immunoglobulin). All can mediate the simplest form of antigen attack (neutralization and agglutination), whereas particular classes specialize in opsonization, activation of the complement system, and stimulation of NK.  NEUTRALIZATION o The antibody blocks an antigen’s activity by binding to it. Block molecules that are use to infect.  AGGLUTINATION o Antigens are frequently neutralized and clumped together simultaneously. Due to the 2 antigen-binding sites (IgM and IgA > 2). o IgG bind equivalent epitopes on 2 separate pathogens, linking them together  OPSONIZATION o Once bound to antibodies, an antigen is effectively opsonized and thus susceptible to phagocytosis. o Antibodies act as opsonins because they can bind to both antigens and phagocytic cells. Triggers the phagocytes to engulf both the antibodies and their targeted prey.  COMPLEMENT ACTIVATION o IgM and IgG activate the complement system, which brings the lysis of bacteria to which the antibodies are bound. o The specific, classical pathway is effective against almost any bacterial cell that has been marked with antibodies.  ENHANCED ACTIVATION OF NATURAL KILLER CELLS o IgG enhance the nonspecific killing action of NK cells. o NK cells produce membrane-perforating molecules that lead to the lysis of these cells. o NK have surface receptors that bind with the constant regions of IgG. Antibodies provide a link between an abnormal cell and the NK cell, serving once against to focus nonspecific responses upon a particular foreign substance. Cell-Mediated Immunity  Antibodies defend against invaders/antigens by floating freely in the blood and lymph; T cells make contact with and respond infected body cells.  Cell-mediated because T cells require direct contact. 23 THE IMMUNE SYSTEM ROLES OF T LYMPHOCYTES IN CELL-MEDIATED IMMUNITY  3 major types of T lymphocytes: helper T cells, cytotoxic T cells, and suppressor T cells.  Helper T cells operate indirectly by secreting cytokines to enhance B cells, cytotoxic T cells, suppressor T cells, and helper T cells themselves. Also enhance macrophages and NK cells (nonspecific).  Cytotoxic T cells directly kill cells infected by viruses or intracellular bacteria and cells that a
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