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Adaptive/Acquired Immunity DENT 516 Adaptive immunity Refers to antigen-specific defense mechanisms that take several days to become protective and are designed to remove a specific antigen. This is the immunity one develops throughout life. There are two major branches of the adaptive immune responses: humoral immunity and cell-mediated immunity. Humoral Immunity • humoral immunity involves the production of antibody molecules in response to an antigen and is mediated by B-lymphocytes. Cell Mediated Immunity CMI involves production of cytotoxic T-lymphocytes, activated macrophages, activated NK cells and cytokines in response to an antigen and is mediated by T-lymphocytes. Antigens • Ags are molecules that elicit an immune response in the body • Ags can be: – Proteins – Polysaccharides – Conjugates of lipids with • Proteins (lipoproteins) • Polysaccharides (glycolipids) Antigens II • Ags that enter body from environment include: – – – – Inhaled macromolecules; e.g., cat hair proteins asthma Ingested macromolecules; e.g. shellfish proteins allergy Molecules introduced beneath the skin; e.g. splinter, vaccine Exogenous antigens Ags generated within the cells of the host: Proteins encoded by viral genes that have infected a cell Aberrant proteins that are encoded by mutant genes; e.g. proteins from mutated genes in cancer cells Endogenous antigens Antigen Presentation Initial immune response to any Ag requires the Ag be recognized by a T cell. This is best exemplified by AIDS w/loss of CD4+ T cells. Dendritic cell B cell Two categories of Ags are processed and presented to T cells by different mechanisms: Exogenous Ags Endogenous Ags T cell activated; cytokines released; Th1, activate M; Th2, activate B cells Exogenous antigens • E. Ag’s (inhaled, ingested, injected), taken up by APCs: – Phagocytic cells; dendritic cells, macrophages – B lymphocytes (produce antibodies) • APCs engulf Ags by endocytosis (endosome-lysosome) Ag degraded into short peptides peptides displayed at cell surface nestled w/i a class II histocompatibility molecule recognized by CD4+ T cells Endogenous Antigens • Ags that are generated w/i a cell; e.g., Mt bug, viral proteins in infected cells • Peptides displayed at cell surface nestled w/I a class I histocompatibility molecule • Recognized by CD8+ T cells • CD8+ T cells are cytotoxic • Have machinery to destroy infected cell T cell activated; kills infected cell B Lymphocytes: A Special Case • • • • • • • • Process Ag by MHC II pathway but: B cells engulf Ag by receptor mediated endocytosis BCRs are surface antibodies anchored in plasma membrane Affinity of BCR for an Ag epitope is so high that the B cell can internalize the Ag at concentrations thousands of times smaller than needed for a macrophage CD4+ T cell recognizes displayed Ag and is stimulated to release cytokines These stimulate B cells to grow into a clone of cells; plasma cells These plasma cells synthesize BCRs with identical binding site for the Ag epitope but w/o the transmembrane tail The Abs are secreted release Th2 cytokines Clonal Expansion Types of T cells