Immunology 2011 Lecture 2 Immune Reactions, Ag/Ab 20 September
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1 Immunology 2011 Lecture 2 Immune Reactions, Ag/Ab 20 September
2 HANDOUTS #1 Roadmap TODAY Immune Reactions, Antigen/Antibody, Core Notes Chapters 1 & 2 and Appendix 1,2 (Precipitin Curve, Ab Labeling)
3 Ag/Ab complexes ANTIGEN Complement Killing of bacteria Inflammation Inactivation of viruses APC Antigen processing (dendritic cells, MΦ et al.) Antigen "presentation" Antigenspecific triggering B T Proliferation Differentiation T H2 T-cell "help" AFC Allergy ANTIBODY T-CELL FUNCTIONS TC T-cell killing: virus-infected cells, transplants effector functions AUTOIMMUNITY Mixed Lymphocyte Reaction (MLR) T H1 Delayed type hypersensitivity, (DTH); e.g. tuberculin reaction T reg Tolerance, suppression AFFERENT CENTRAL EFFERENT THREE "LIMBS" OF THE IMMUNE RESPONSE
4 Blood monocyte Phagocytic, APC, can process and present antigen. Tissue-resident dendritic cells are most important APCs.
5 Blood lymphocyte T cell or B cell, antigen-specific generation of humoral and cell-mediated immune responses.
6 Organs of the Immune System APCs, T-cells and B-cells populate Lymphoid Tissues Lymph nodes Spleen Peyer s patches et al (+Thymus and Bone Marrow) & travel via the blood and lymph
7 When the Immune System Goes Wrong Infection (bacteria, viruses, other parasites) Immunodeficiency (congenital, acquired, iatrogenic) Allergy (food/animals/drugs, hay fever & asthma ) Autoimmune disease (rheumatoid arthritis, lupus etc.) Contact dermatitis (poison oak, affordable jewelry) Transplant rejection (kidney, heart, lung, liver etc.) Transfusion reactions (blood typing)
8 Innate Immunity No adaptive specificity, no memory Mucous membranes, phagocytes (RES), complement, anti-bacterial peptides Adaptive Immunity Specificity, memory B Cells, T Cells Activation of the innate immune system is required to trigger adaptive immune responses. Adaptive immune responses may recruit participation of cells of innate immunity (PMN, MФ, etc).
9 Humoral Immunity (HI) Transferred by serum mediated by antibodies Cell-Mediated Immunity (CMI) Not transferred by serum mediated by T-cells (& other inflammatory cells) Humoral immunity: protection against extracellular parasites. Cell-mediated immunity: protection against intracellular parasites.
10 Immunization vs. challenge Live Pneumococcus DIES Naive immune Killed Pneumococcus Live Pneumococcus SURVIVES Naive wait 2 weeks Immune "Active Immunity" Immune TRANSFER SERUM Naive Live Pneumococcus SURVIVES immune "Passive Immunity" Defining Humoral Immunity: resistance to pneumococcus
11 APC Antigen processing (dendritic cells, MΦ et al.) Antigen "presentation" Ag/Ab complexes Antigenspecific triggering B T ANTIGEN Proliferation Differentiation T H2 T H1 T-cell "help" Complement AFC ANTIBODY Killing of bacteria Inflammation Inactivation of viruses Allergy AUTOIMMUNITY T-CELL FUNCTIONS TC T-cell killing: virus-infected cells, transplants Mixed Lymphocyte Reaction (MLR) Delayed type hypersensitivity, (DTH); e.g. tuberculin reaction T reg Tolerance, suppression AFFERENT CENTRAL EFFERENT THREE "LIMBS" OF THE IMMUNE RESPONSE
12 Three Limbs of the Immune Response Ag uptake by APC Ag Processing & Display Ag Presentation, APC/T-Cell interaction Ag-specific triggering of T and B Cells; Proliferation & differentiation Effector functions: T C Target Cell Killing T H1/DTH Delayed Type Hypersensitivity T H2 /B-cells, Ab killing/inactivation of targets Complement, killing & immune complexes T reg Suppression/regulation; Tolerance Afferent Central Efferent
13 ANTIBODY Binds antigen ANTIGEN Is bound by antibody EPITOPE (= antigenic determinant ) Minimum target structure to which Ab binds
14 ANTIGEN Serves as target for immune response IMMUNOGEN Elicits immune response Substance Mol. weight Immunogen? Antigen? 1) BSA 68,000 yes yes 2) DNP (free) ~200 no yes 3) DNP10-BSA 70,000 BSA yes yes DNP yes yes 4) "clarified" BSA 68,000 no yes ADJUVANT Increases immune response * * but generates tolerance
15 Manifestations of Antibody Physical Effects Precipitation (soluble Ag) Agglutination (particulate Ag) Binding Biological Effects Protection Immobilization Cytolysis Opsonization Defining Property of Abs: SPECIFIC BINDING..but binding by itself is invisible
16 Ab Ag Antibody Precipitation: The Precipitin Curve no precipitation PRECIPITATION no precipitaton Antigen excess Equivalence Antibody excess Amount of ppt. Amount of added Ab See Antibody Assays slide show on course web site.
17 Manifestations of Antibody Physical Effects Precipitation (soluble Ag) Agglutination (particulate Ag) Binding Biological Effects Protection Immobilization Cytolysis Opsonization Defining Property of Abs: SPECIFIC BINDING
18 View the Antibody Assays Slide Show on the course web site, illustrating: Precipitation (x3) Agglutination (x2) ELISA Western blot Immunofluorescence (x2) Serum electrophoresis
19 Peter Parham, Nature 344:709 (1990)
20 APC Antigen processing (dendritic cells, MΦ et al.) Antigen "presentation" Ag/Ab complexes next 4 lectures Antigenspecific triggering B T ANTIGEN Proliferation Differentiation T H2 T H1 T-cell "help" Complement AFC ANTIBODY T-CELL FUNCTIONS TC Killing of bacteria Inflammation Inactivation of viruses Allergy T-cell killing: virus-infected cells, transplants Mixed Lymphocyte Reaction (MLR) Delayed type hypersensitivity, (DTH); e.g. tuberculin reaction AUTOIMMUNITY T reg Tolerance, suppression AFFERENT CENTRAL EFFERENT THREE "LIMBS" OF THE IMMUNE RESPONSE
21 TOMORROW & THURSDAY Antibody Structure I & II Chapters 3, 4 Appendix 3-7 (Ouchterlony, Affinity Chromatography, RIA, Equilibrium Dialysis, Cross-Reactivity)
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