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Chapter 6
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Adaptive Immunity “third line of defense” Develops more slowly Specific Memory
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Adaptive Immunity Antigens – “foreign or non self” (Ag= foreign proteins) ◦ Viruses, bacteria, cancer, fungi or parasites ◦ Noninfectious – pollens, foods, bee venoms ◦ Drugs, vaccines, transfusions and transplants
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Adaptive Immunity Principal cells : Lymphocytes ◦ Accessory cells : APC & dendritic cells ◦ Effector cells B cells → antibodies to blood → Ag T cells → attack Ag directly Functionally ◦ Regulatory ◦ Effector Specific ◦ Each cell recognizes only ONE specific Ag
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25-35% of blood leukocytes 99% reside in the lymph glands 60-70% of blood lymphocytes are T-cells and 10-20% are B-cells Foreign protein recognition :”surface receptor proteins-unique” ◦ B-cells: membrane bound immunoglobulin ◦ T-cells: self-recognition protein(major histocompatibility complex)
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“self from non self” Chromosome # 6 Two Classes Class I *: endogenous pathogens -viruses & cancer Cytotoxic T cells… “must destroy me” ◦ Class II : extracellular pathogens - bacteria & toxins Phagocytic cells: macrophages, dendritic cells, B lymphocytes : Ag binds with MHC II Helper T cell (CD4+) Human Leukocyte Antigens:WBCs ◦ Multiple allelles: A (120 genes) & B (250 genes) ◦ Halotype: inherited unit * all nucleated cells… not on RBCs
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Class I … “all nucleated cells” (endogenous antigens)* Function:present processed antigen to cytotoxic CD8+ T cells or NK cells “constant screening” * Seen as abnormal…autoimmune disease
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Class II …APC (dendritic, B cells, macrophage) (exogenous antigens) Function: presents processed antigen fragment to CD4+ T cells effective interaction among immune cells* *Figure:6-1
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“Additional membrane bound proteins” Uses ◦ Aid the function of the immune cells ◦ Define the functionally distinct subset of cells CD4+ helper T cells – binding receptor: from APCs CD8+ cytotoxic T cells- binding receptor: from all nucleated cells
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Adaptive Immunity Clonal diversity – 1 st phase – fetus ◦ Recognition of millions* of foreign Ag ◦ Large population of T & B cells ◦ Develop in primary lymphoid organ (thymus, bone marrow) ◦ Migrate to secondary lymphoid organs * 10 8 or 100 million foreign antigens(proteins)
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Generation of Clonal Diversity “primary lymphoid organ – fetus” Lymphoid stem cell B and T cells recognize more than 10 8 antigens B lymphocytes – bone marrow “hormones” – to secondary lymphoid organs* T lymphocytes – thymus “hormones” to second lymphoid organs* *lymph nodes & spleen
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Secretory (Mucosal) Immune System Lymphoid tissue that protects the external surface of the body Ab present in tears, sweat, saliva, mucus and breast milk. IgA dominant immunoglobulin ◦ Prevent attachment and invasion of pathogens
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Adaptive Immunity “two arms” Humoral – B cells ◦ Antibodies – bacteria, viruses, and toxins Cell mediated – T cells ◦ Subpopulations React directly with Ag on cell surfaces – NK(see next slide) Stimulate other leukocytes (cell to cell or cytokines) T Cytotoxic cells – viruses infected cells and cancer
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“ lymphocytes ” :functionally & phenotypically distinct from T cells, B cells, and monocyte-macrophages ◦ Automatically kill foreign cells: programmed ◦ No activation as with cytotoxic T cells ◦ Inhibition with contact of normal host MHC molecules
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Antigens “molecule that reacts with antibodies or receptors on B and T cells” Immunogens-antibodies Epitope – antigenic determinant (recognized) Paratope – Ag binding site (antibody or lymphocyte)
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Antigens Self-antigen – every cell*, genetically determined (MHC), HLAs + *glycoproteins – not RBC + human leukocyte antigens Tolerance
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Humoral* Immune Response Antibodies ◦ Immunoglobulins ◦ Plasma cells ◦ Classes IgG, IgA, IgM, IgE and IgD *fluid
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Classes of Immunoglobul ins IgG ◦ Most abundant (80 to 85%) ◦ Transported across the placenta ◦ Four classes IgA ◦ Two classes IgA 1 – blood IgA 2 – body secretions
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Classes of Immunoglobulins IgM – Largest – First Ab produced during 1° response to an Ag – Synthesized during fetal life IgD – Low concentration – Ag receptor on surface of early B cells IgE – Allergic responses – Parasite infections
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Functions of Antibodies Direct effects ◦ Neutralization ◦ Agglutination ◦ Precipitation Indirect effects ◦ Opsonization ◦ Complement
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B Cell Antigen Receptor Surface of B cell Consists ◦ Antigen – recognition molecule : IgM, IgG monomer ◦ Intracellular signaling molecules
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Cell Mediated Immune Response Mature T cells – 1.Cytotoxic (Tc) – attack and destroy directly – 2.Regulatory helper T (Th) – controls Cell mediated Humoral mediate Suppressors (Ts) – 3.Memory cells “viruses, tumors, pathogens resistant to neutrophils and macrophages”
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T Cell Recognition of a Target Cell T cell receptor complex ◦ Antibody-like transmembrane protein ◦ Accessory proteins for intracellular signaling Antigen presentation molecules ◦ By antigen presenting cells ◦ Major histocompatibility complex (dendritic cells*, macrophages, B-lymphocytes) ◦ *Nobel Prize Medicine & Physiology 2011: Beutler, Hoffman & Steinman
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Functions of T-lymphocyte “Killing abnormal cell” ◦ Cytotoxic T lymphocytes (viruses, tumors) Attach to target cell : MHC-I molecules Appropriate CD molecules Activate macrophages ◦ Cytokines – chronic inflammation Regulate immune response ◦ T-helper (Th) cell – humoral & cellular ◦ T-suppressor cells – affects immune response
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Primary and Secondary Immune Responses Primary ◦ Initial exposure ◦ Latent period (B cell differentiation) ◦ After 5 - 7 days – IgM antibodies detected ◦ An IgG response follows
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Primary and Secondary Immune Responses Secondary ◦ More rapid ◦ Large amounts of Ab are produced ◦ Rapid response - 2° to memory cells ◦ IgM – similar to 1° response, IgG – greater number Figure 6-15 Page 161 ◦ “MEMORY”
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Active vs. Passive Immunity Active Immunity ◦ Antibodies or T cells produced after either a natural exposure to an antigen or after immunization Passive Immunity ◦ Preformed Ab or T lymphocytes are transferred from a donor to a recipient. ◦ Example: IgG for hepatitis A exposure : tetanus toxoid
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