Adaptive Immunity 1 PDF

Adaptive Immunity I-III Dr. M. Grant, [email protected]  Adaptive Immunity I: Key Elements of Adaptive Immunity- Objectives 1) Distinguish lymphocytes that mediate adaptive immunity from natural killer cells, myeloid lineage cells and other hematopoietic cells 2) Describ...

Adaptive Immunity I-III Dr. M. Grant, [email protected]  Adaptive Immunity I: Key Elements of Adaptive Immunity- Objectives 1) Distinguish lymphocytes that mediate adaptive immunity from natural killer cells, myeloid lineage cells and other hematopoietic cells 2) Describe how natural killer cells are linked with adaptive immunity 3) Distinguish T and B lymphocyte mechanisms of antigen recognition 4) Distinguish exogenous and endogenous antigen presentation pathways 5) Describe how the lymphatic system contributes to adaptive immunity 6) List key features of adaptive immunity Key Cellular Elements of Adaptive Immunity Adaptive immunity is mediated by lymphocytes- T cells, B cells and arguably, natural killer (NK) cells. Three different types of lymphocyte in larger family of leukocytes (white blood cells). B and T cells are antigen-specific Innate lymphoid and have highly diverse, cells specialized receptor repertoires generated by a process called somatic recombination.  Antigen Recognition by B and T Lymphocytes is Fundamentally Different B cells recognize antigens in free native form (direct recognition). T cells recognize antigens (proteins) that are enzymatically processed into linear peptides and presented in combination with MHC molecules on antigen-presenting cells (associative recognition). Information processing provides the context for T cell response.  Two Distinct Pathways Process Antigens for Presentation to T cells Two antigen processing pathways Exogenous and Endogenous Two classes of MHC molecule MHC I and MHC II Two classes of T cell Helper T cell (CD4) and Cytotoxic T cell (CD8)  Mechanisms of Adaptive Immunity (Humoral) B cells make antibodies (humoral With “help“ from T cells, B cells immunity) and function as differentiate to make more antigen-presenting cells (APC). antibodies, modify antibodies to better recognize antigens (somatic hypermutation/affinity maturation) Antibodies are versions of the and change the tissue distribution antigen-specific receptor and biological functions of the expressed on B cell surface. antibodies they make (isotype switching). Begins as an intrinsic process…like a reflex response. Integrated response involving T-B co-operation and coordination.  Antibody Functions Opsonization Complement Activation Antibody Functions Toxin neutralization and clearance Antibody Functions Microbe Neutralization  Mechanisms of Adaptive Immunity (Cell-mediated) T cells can kill infected or NK cells have no antigen specific transformed cells expressing non- receptors, but react to specific self or modified self-antigens (CD8 + antigens through antibody bridges. cytotoxic T cells) and make cytokines that affect the function of other cells Mediate antibody-dependent cell- CD4+ >>> CD8+ (cell-mediated mediated cytotoxicity (ADCC) and immunity). release cytokines. Actions are triggered through engagement of antigen-specific receptors with MHC/peptide complexes.  Lymphatic System Provides Infrastructure for Adaptive Immunity Immune responses initiated in lymph nodes through cell to cell interactions. Nodes are rich in antigen presenting cells that bring antigens from periphery. B cells live there. T cells traffic through. Multiple layers and pathways of co-operation required for effective functioning of the adaptive immune system. Lymphatic System Key to Adaptive Immunity Low pressure circulatory system Collects residual fluid from tissues, filters pathogenic material, empties into subclavian veins Lymphatic system extends throughout body and consists of: lymphatic vessels, lymph nodes, bone marrow, spleen, thymus and mucosa–associated lymphoid tissue  Key Features of Adaptive Immunity Specificity- exposed to particular antigen, responds to that antigen and just that antigen. Memory- “remembers” antigen for more rapid & stronger response to subsequent exposures. Self tolerance- normally does not respond to self antigens Self tolerance depends upon 1) selection of antigen-specific B and T cell repertoires and 2) on post-selection regulation. Summary: key elements and interactions in adaptive immunity Elements- T cells, B cells, NK cells, antigen-presenting cells, accessory cells, MHC molecules, antibodies, cytokines Interactions- T cell- T cell (enhanced proliferation and differentiation, regulation) T cell- accessory cell (activation of phagocytosis, antimicrobial activity) T cell- APC (antigen presentation) T cell- B cell (somatic hypermutation, isotype switching) NK cell- Ab (antibody dependent cell-mediated cytotoxicity)