Transcript Chapter 6
Chapter 6 Adaptive Immunity “third line of defense” Develops more slowly Specific Memory 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 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 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) “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 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 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 “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 Adaptive Immunity Clonal diversity – 1st 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 *108 or 100 million foreign antigens(proteins) Generation of Clonal Diversity “primary lymphoid organ – fetus” Lymphoid stem cell B and T cells recognize more than 108 antigens B lymphocytes – bone marrow “hormones” – to secondary lymphoid organs* T lymphocytes – thymus “hormones” to second lymphoid organs* *lymph nodes & spleen 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 Adaptive Immunity “two arms” Humoral – ◦ Antibodies – Cell B cells bacteria, viruses, and toxins 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 “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 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) Antigens Self-antigen – every cell*, genetically determined (MHC), HLAs+ *glycoproteins – not RBC + human leukocyte antigens Tolerance Humoral* Immune Response Antibodies ◦ Immunoglobulins ◦Plasma cells ◦ Classes IgG, IgA, IgM, IgE and IgD *fluid Classes of Immunoglobulins IgG ◦ Most abundant (80 to 85%) ◦ Transported across the placenta ◦ Four classes IgA ◦ Two classes IgA1 – blood IgA2 – body secretions 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 Functions of Antibodies Direct effects ◦ Neutralization ◦ Agglutination ◦ Precipitation Indirect effects ◦ Opsonization ◦ Complement B Cell Antigen Receptor Surface of B cell Consists ◦ Antigen – recognition molecule : monomer ◦ Intracellular signaling molecules IgM,IgG 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” 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 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 Primary and Secondary Immune Responses Primary ◦ Initial exposure ◦ Latent period (B cell differentiation) ◦ After 5 - 7 days – IgM antibodies detected ◦ An IgG response follows 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” 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