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Transcript
The objectives of this course How can you produce an antiserum or aantibody t o y with t the t e desired es e characteristics? c a acte st cs? Study the basics of the immune system, especially the (humoral) immune response How can you obtain the best possible result with a ggiven antiserum/antibodyy in a given g application? Study the basics of the antibody structure and the mechanism of antibody-target interactions Non-Adaptive versus Adaptive immunity has low specificity needs no induction time has no memory acts through anatomic barriers (*) serves in the early stage of d f defense high specificity takes several days to put in place h memory has acts through lymphocytes and accessory cells ll serves in the later phase of events t ... but remember : the two collaborate! (*) physiological barriers, endocytic and phagocytic barriers, inflammatory barriers The inflammatoryy response p tissue dammage bacteria vasoactive & chemotactic h i factors f serum proteins phagocytic cells migrate exudate serum p proteins, complement, antibody, ... capillary p y The four capital signs of inflammation: tumor, rubor, calor & dolor Endocytosis (Phagocytosis and Pinocytosis): it's like eating and drinking ... Phagocytosis : the "eating" eating of particulate matter by a cell Pinocytosis: the "drinking" of extracellular fluid, containing macromolecules 11 2 3 4 5 3 phagosome moves toward lysosome 2 ingestion into phagosome 4 fusion of phagosome and lysosome 1 attachment to pseudopodia 5 digestion & elimination The cells that do the work bone marrow pluripotent hematopoietic stem cell bone marrow common lymphoid progenitor myeloid progenitor y megakaryocyte g y y erythroblast blood ppolymorphonuclear y p leucocytes y B-cell T-cell effector cells plasma cell activated T-cell basophil eosinophil neutrophil ? monocyte tissues mast cell macrophage platelets erythrocyte Key players of the immune system : the lymphocytes Small lymphocytes are inactive cells: condensed chromatin little cytoplasm small size no RER B-cells B cells antigen-recognition sites T-cells T cells antigen-recognition site The "dogmas" of immunology All the antigen-recognition sites of a particular lymphocyte are identical: one cell - one antigen . Each lymphocyte generates a unique receptor by rearranging its receptor genes; there there'ss literally millions of possibilities: "diversity". diversity . Lymphocytes recognizing ubiquitous self-antigens are eliminated p byy a pprocess called "clonal deletion",, leadingg to duringg development "self-tolerance". A lymphocyte y p y needs to meet its antigen g before it can get g activated and start producing identical daughter cells, a process called "clonal expansion". This ensures the specificity of the immune response. Upon encounter of that antigen, some of these daughter cells will survive, even after the antigen has been eliminated: these cells (("memoryy cells")) are the basis of immunological g memory. y Lymphocytes are "educated" in the central lymphoid organs Initial receptor repertoire Ubi it Ubiquitous self lf antigens ti Self antigens bind to receptors on newly formed cells Anti-self cells die (clonal deletion) leaving mature self-tolerant epe o e reperoire B-cells in the Bursa of Fabricius (Bone marrow) T-cells cells in the Thymus The clonal selection theory Removal of potentially self-reactive immature lymphocytes by clonal deletion Negative selection self antigens self antigens Pool of mature naive lymphocytes foreign antigen Proliferation of activated specific lymphocytes to form a clone Differentiation to effector cells Effector cells eliminate antigens Differentiation into resting memory cells Memory cells respond more efficiently to antigen P i i selection Positive l i Lymphocytes y p y at work ... 1) antigen-receptor binding 2) activation by nearby T-cell T cell B-lymphocyte 1) antigen-receptor binding 2) Co-stimulation by antigen-presenting cell (APC) antigen- presenting cell proliferation (clonal expansion) and differentiation to effector function T-lymphocyte The Professional Antigen-Presenting Cells (APC) B-lymphocyte Macrophage Dendritic cell B cell activation by helper CD4 cells B-cell 1) Antigen bound by B-cell B cell surface receptor 2) Antigen internalized and degraded g to ppeptide p fragments g 3) Fragments bind to MHC-II and are transported to cell surface 4) Recognition by T Helper cell and activation of B-cell When the bugs invade ... Virus infects macrophage Bacterium macrophage infects Viral proteins synthesized in cytosol Bacterium gets digested into peptide fragments Fragments of viral proteins bound by MHC class I in ER Bacterial fragments are bound by MHC class II in vesicles Bound peptides presented at cell surface by MHCclass I Bound peptides presented at cell surface by MHCclass II Cytotoxic T cell recognizes this complex and kills the infected cell T helper cell recognizes this complex and activates APC T cell - APC interaction in close up p T Helper -cell TCR C Cytotoxic i T T-cellll TCR CD4 peptide MHC-II peptide CD8 MHC-I APC Nucleated cell g of the immune system y The organs Naive lymphocytes enter lymph nodes f from blood bl d adenoid tonsil right subclavian vein lymph y p node kidney appendix lymphatics Lymphocytes and lymph return to blood via thoracic h dduct left subclavian vein thymus thymus heart thoracic duct spleen Peyer's patch in small intestine large intestine bone bone marrow marrow lymph node infected peripheral tissue Antigens from sites of infection reach lymph nodes via lymphatics Meeting point : the lymph node primary lymphoid follicle afferent lymphatic vessel paracortical area (mostly T-cells) secundary lymphoid follicle (mostly B-cells) cortex medullary cords (macrophages and plasma cells medullary sinus artery vein efferent lymphatic vessel marginal sinus antigen naive lymphocytes effector lymphocytes