Unformatted text preview: Chapter 32: Chapter 32: Specific Immunity Specific Immunity Specific Immunity Recognizes things as being nonself and produces a response to these foreign entities Foreign entities = antigens Response has memory Referred to as the anamnestic response At secondary exposure to the same antigens, the response is faster and more effective than at the primary exposure Response has specificity to an individual antigen Two branches of defense Humoral (Antibodymediated) Cellmediated Immunity Specific Immunity Response Time Specific Immunity Response Time Specific Immunity Terms Specific Immunity Terms Antigens: chemicals present on viral/bacterial surfaces that react with antibodies or lymphocytes Immunogen: an antigen that induces immune response Most are foreign, high molecular weight such as proteins, polysaccharides lipids, and nucleic acids Antibodies: glycoproteins that react specifically with antigens Bind to antigenic determinant (also called epitope), which is a small region of antigen Haptens : small molecules which are not antigenic by themselves Can become antigenic when combined with a larger carrier protein Antigens: Epitopes and Haptens Antigens: Epitopes and Haptens Types of Acquired Immunity Types of Acquired Immunity
1. Naturallyacquired and active immunity: Host is exposed to an antigen (is infected) and develops its own antibodies against the pathogen Host retains a memory of this antigen and can quickly produce more antibodies upon secondary exposure to antigen Example: Influenza recovery using only overthecounter drugs; development of lasting immunity to that specific strain 2. Naturallyacquired and passive immunity: Host is provided with preformed antibodies made by someone else who has developed immunity to the disease Host has no memory of antigen or antibody production of its own Example: Newborn’s specific immunity comes from mom’s IgA (secreted) and IgG (crosses placenta) works for about the first 2 months of life Host is vaccinated with either an attenuated (weakened) or killed pathogen (or sometimes simply the purified antigen alone) Due to mere presence of antigen, host makes antibodies to this antigen without a fullblown infection occurring and retains a memory of the antigen and antibodies against it Example: Measles vaccinations 3. Artificiallyacquired and active immunity: 4. Artificiallyacquired and passive immunity: Host is provided with preformed antibodies against pathogen via vaccination Antibodies are formed by other infected individuals or lab animals and purified from their serum Host has no memory of antigen or antibody production of its own Example: Gamma globulin injections given to immunocompromised patients Types of Acquired Immunity Types of Acquired Immunity Vaccinations Vaccinations Living attenuated agents (modified): Attenuated agents are antigenic and can replicate, but are modified to be incapable of causing disease under normal circumstances Inactivated immunizing agents: Killed bacteria/virus bacterial toxins (toxoids) Inactivated agent vaccines may contain inactivated whole agents or subunits (portions) of the agent Recombinant vaccines: (Genetically engineered) Can have edible vaccines where antigens are engineered into food sources Antibodies: General Antibodies: General Characteristics Also called immunoglobulins (Ig)
Made of glycoproteins 5 human classes: IgM, IgG, IgA, IgD, IgE IgM, pentamer; IgA often dimer; others monomers Anatomy of an antibody: Yshaped: Have 2 Heavy (H) and 2 Light (L) chains Each has constant (Fc) and variable regions (Fv) Each monomer has 2 identical antigen binding sites (Fab regions) – the Fv regions are at the open terminals Antigenantibody binding based on complementary fit of epitope region of antigen with Fv of antibody Antibody Anatomy Antibody Anatomy
Pentamer: IgM Dimer: IgA Monomers: IgG, IgD, IgE IgG: Human Immunoglobulins Human Immunoglobulins Most abundant immunoglobulin in body fluids (80%) Only antibody to cross placental membrane Involved in opsonization: Fc region attracts phagocytes Activates classical pathway of complement system IgM: Second most abundant (10%) in body fluids First class produced in primary response Acts to agglutinate antigens to enhance phagocytosis Found as a membrane bound antibody on B cells Also activates classical pathway of complement system IgA: (sIgA) Found secreted in mucous membranes, saliva, and breastmilk Found on activated B cells Interaction with antigens signals B memory cells to produce antibodies IgD: IgE: Associated with allergy or hypersensitivity reactions Fc regions bind to basophils & mast cells to stimulate release of histamines Neutralization Actions of Antibodies Actions of Antibodies Antibodies bind to antigens Block attachment to host cell receptors Opsonization Classical path of complement More binding sites for phagocytic receptors Precipitation Soluble antigens bind and are precipitated as ‘immune complexes’ Crosslinking of antigens forms larger targets for phagocytes Alternative path of complement Agglutination Complement Fixation MAC induced cell lysis Actions of Antibodies Actions of Antibodies Antibodies in Phagocytosis Antibodies in Phagocytosis Recognition of Foreignness Recognition of Foreignness Major histocompatability complex (MHC) Genes which distinguish self (human) from nonself (invaders) Also known as Human Leukocyte Antigen complex (HLA) Three classes of MHC Class I Membrane protein found on all nucleated cells Membrane protein found on antigen presenting cells: macrophages, dendritic cells and B cells Secreted chemicals, not involved in self/nonself recognition and are not membrane proteins Class II Class III Responsible for cellmediated immunity; mature in the thymus Also helps in humoral immune responses (Th cells) aiding in antibody production Have Tcell receptors (TCR) for antigens on their surfaces T cells also have surface markers called cluster of differentiation (CD proteins) Lymphocytes: T Cells Lymphocytes: T Cells All T cells have CD3 proteins associated with the TCR Also have either CD4 or CD8 proteins on their surfaces which interact with MHC proteins on leukocytes Different T cell subsets have different functions Ts cells (suppressor) suppress immune responses Th cells (helper) produce cytokines, activate other cells Tc cells (cytotoxic) cause cell death Have CD4 surface markers which serve as coreceptors for MHC II proteins Also called CD4+ T cells Play roles in both humoral and cellmediated immunity Have CD8 surface markers which serve as coreceptors for MHC I proteins Also called CD8+ T cells Play a role only in cellmediated immunity Lymphocytes: B Cells Lymphocytes: B Cells B cells: responsible for the antibody response and humoral (antibodymediated) immunity; mature in the bone marrow Carry IgM or IgD on their cell surfaces = B Cell Receptors (BCR) Antigenpresenting B cells can leave circulation, go to lymphoid tissues become plasma cells Lymph nodes allow interactions between different lymphocytes, macrophages, other cells, & cytokines important for communication Humoral vs. CellMediated Immunity Humoral vs. CellMediated Immunity Humoral (B Cell) Immunity Humoral (B Cell) Immunity Initial reaction antibody on surface of B cell must recognize antigen Antigenpresenting cells, such as macrophages, help B cells ‘find’ the antigen Usually needs help from Th cells to be able to produce antibody – ‘the baton relay’ Th cells act as an intermediate to pass the antigen from a macrophage to a B cell via class 2 MHC proteins and CD4 receptors Th cells also act to stimulate B cell cloning and differentiation by releasing cytokines Plasma cells can then develop antibodies while B memory cells retain the antigen for future reference Antigen Recognition and Antigen Recognition and Antibody Production Antigen Recognition Antigen Recognition and Antibody Production CellMediated Immunity CellMediated Immunity Tc (cytotoxic) cells can kill host cells Directed against antigens that are on whole cells (virusinfected or tumor cells) Infected cells use class I MHC proteins to display antigen on outside of cell membrane Tc cells recognize infected cells by binding their CD8 proteins to the displayed antigen/class I MHC complexes Contents in Tc granules are released near the target cell, killing the target cell but not the Tc cell Perforinkills target cell by forming a pore through the target cell membrane CellMediated Immunity CellMediated Immunity Humoral vs. CellMediated Immunity Humoral vs. CellMediated Immunity Th Cell Activation of Macrophages Th Cell Activation of Macrophages
Cooperation between nonspecific and specific defense systems Th cells release cytokines which stimulate the phagocyte to fuse phagosomes with lysozomes Fusion introduces digestive enzymes to trapped bacteria and kill cells Hypersensitivity Reactions Hypersensitivity Reactions Excessive immune complex (antigenantibody) formations are produced faster than the immune system cells can deal with Always result from secondary exposure to an antigen 4 main classes: Type I: Allergic Reactions Type II: Cytolytic or Cytotoxic Hypersensitivity Type III: Serum Sickness Hypersensitivity Type IV: Delayed CellMediated Hypersensitivity Type I Hypersensitivity: Allergic Reactions Type I Hypersensitivity: Allergic Reactions Mediated by IgE which stimulates mast cells to release histamines and other chemicals Examples: insect stings, nut allergies, drug allergies, hay fever Anaphalaxis difficulty breathing due to many chemical mediators like histamines being released by the mast cells Desensitization (i.e. allergy shots) Series of injections of small doses of antigen beneath the skin Elicits an increase in the level of IgG antibodies IgG surrounds the antigen and prevents its interaction with IgE Type I Hypersensitivity: Allergic Reactions Type I Hypersensitivity: Allergic Reactions Type II: Cytolytic/Cytotoxic Hypersensitivity Type II: Cytolytic/Cytotoxic Hypersensitivity Destruction of cells either by lysis or toxic mediators IgG or IgM mediated and are directed against cell surface antigens – HLA proteins Example 1: Blood transfusions from outside of own blood type group ABO antigens on surface of blood cells are distinguished and foreign cells are destroyed Results in universal donors (type O) and universal recipients (type AB) Example 2: Rh factor and pregnancy Rh mother first pregnancy with Rh+ child is not problematic for child blood does not mix during development, only at birth At the birth of the first Rh+ child, an Rh mom is exposed to Rh+ antigen and develops antibodies against it In a subsequent pregnancy of an Rh+ child, mom has antibodies against it Recall IgG crosses placental membranes and can attack the fetus’ cells in utero Type III: Serum Sickness Hypersensitivity Type III: Serum Sickness Hypersensitivity Immune complexes form and cause serious inflammation response Vasculitis, glomerulonephritis and arthritis are associated Complexes are insoluble and deposit in the kidney and liver, blocking proper circulation Normally the complexes would be removed by macrophages and monocytes Primarily IgG mediated Type IV: CellMediated Delayed Type IV: CellMediated Delayed Hypersensitivity Tcell mediated, not by antibodies Often occurs 23 days after contact with the antigen Examples: contact dermatitis, poison ivy/oak/sumac, also the basis for Tb skin test Involved in tissue/transplant rejection and death of cancer cells Antigens presented to Class I MHC on Th cells from macrophages Contact of antigen with the Th cell releases cytokines which attract lymphocytes/basophils/macrophages Certain cytokines bind to receptors on outsides of cells and mark them for destruction by these attracted macrophages Autoimmune Diseases Autoimmune Diseases Genetic, viral and endocrine factors influence the development of autoimmune diseases Estrogen production level seems to be a trigger of onset autoimmune disease more prevalent in women, often develops during pregnancy Androgen acts as a suppressor of the disease (male hormones) Destruction of self/own tissues and cells Examples: Rheumatoid arthritis and Lupus Immunodeficiency Diseases Immunodeficiency Diseases Host’s specific immune system is somehow compromised Either B cell or T cell production is limited or completely prevented If B cells are the target: Antibodies are not produced, and individual is severely limited to outside world contact Life in a plastic bubble Stimulation and regulation of the nonspecific immune system by cytokine release is problematic AIDS is an acquired immunodeficiency disease where T cells are inhibited or destroyed by the virus There are also genetic conditions where individuals are born with defective thymus glands and Tcell maturation does not occur If T cells are the target: ...
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- Fall '09