Adaptive Immune System

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1 Short Course on Immunology Adaptive Immune System Bhargavi Duvvuri Ph.D IIIrd Year (Immunology) Supervisor Dr.Gillian E Wu Professor, School of Kinesiology and Health Sciences York University, Toronto

2 Immune System Innate Immunity (Present before infection) Adaptive Immunity (Develops in response to infection)

3 Adaptive Immunity Immunity that an organism develops and adapts to recognize, eliminate and remember specific pathogens (antigen) What is an antigen? An antigen is any substance that elicits an immune response.

4 Innate vs. Adaptive Immunity Attribute Response time Specificity Diversity Memory response Self/non-self discrimination Major cell types Innate immunity Minutes/hours Broad recognition: lessspecific Limited number of germ line-encoded receptors None Perfect Phagocytes, natural killer cells, dendritic cells Adaptive immunity Days Highly specific Highly diverse; Adaptive: G.O.D Present Very good T cells, B cells, antigenpresenting cells (APC) Source: Kuby Immunology, Sixth Edition

5 Players and their effector functions

6 Duality of Adaptive Immune System Humoral (Antibody-Mediated) Immunity (Extra cellular pathogens) Cell Mediated Immunity (Intra cellular pathogens)

7 Humoral (Antibody-Mediated) Immunity Involves production of antibodies against foreign antigens. Antibodies (membrane bound and soluble) are produced by a subset of lymphocytes called B cells. (Bone( marrow) Antibodies can recognize free antigen on their own. B cell differentiation (T cells help) B cell Plasma cells :Secrete antibodies Memory B cells: Secondary response Detect and prevent the entry of extracellular pathogens

8 Antibody structure Variable region (Fab) Constant region (Fc( Fc): effector functions Five classes of antibodies:igg, IgA, IgM, IgD,, and IgE.. Each have a different function.

9 Production of antibodies Pathogen (virus or bacteria) Pathogen is internalized and degraded B cell B cell binds pathogen Plasma cells cytokine T H 2 MHC II B cell Peptides from the pathogen are presented (MHC II) to the T cell resulting in the activation of the B cell B cell proliferation B cells differentiate into antibody-secreting plasma cells Produce antibodies against pathogen

10 Cell Mediated Immunity Involves specialized set of lymphocytes called T cells (Thymus)( with membrane bound T cell receptor (TCR). Two main types: 1. CD4+ (TH1 and TH2): Stimulate other immune cells. 2. CD8+ Cytotoxic T cells (T C ): Kill intracellularly-infected cells. Recognition of processed Ag in the context of Major Histocompatability complex (MHC) T cells detect presence of intracellular pathogens And T cells, the cells that help, are the brains of the immune system.

11 Antigen Presentation to T cells: MHC Restriction Target cell Class I MHC Antigen presenting cell Class II MHC CD8 CD4 (endogenous antigen) 8-10 amino acid peptide (exogenous antigen) 13aa or more peptide) TCR complex CD8 + T cell MHC I: on most of the cells TCR complex CD4+ T cell MHC II: Dendritic cells, macrophages and B cells

12 Cells that link the innate and adaptive immune systems: Antigen Presenting Cells (APCs) 1. Dendritic cells 2. Macrophages 3. B lymphocytes Ag is internalized Stimulates T-helper cells they provide co-stimulatory signals

13 Cytokines Cytokines are soluble protein factors that can activate many cells Ex. Cytokines secreted by T H CTLs, MΦ, NK: IL-4, IL-5 etc. can affect B-cells,

14 Cytokine functions

15 Antigen Recognition by T-cellsT Cytotoxic T cells (CD8) recognize antigen presented by MHC I and kills the cell Kills T H 1 cells (CD4) recognize antigen presented by MHC II and activates macrophages Activates T H 2 cells (CD4) recognize antigen presented by MHC II and activates B cells Activates Cytotoxic T cell MHC I Virusinfected cell T H 1 MHC II Macrophage T H 2 MHC II B cell Apoptotic cell Dead intracellular bacteria Anti-toxin antibodies

16 Characteristics of Adaptive Immune System Antigenic Specificity Diversity Memory response Self/non-self discrimination

17 Antigenic specificity Is due to the CLONAL EXPANSION of only those lymphocytes with antigen specific receptors. B lymphocytes BCR/Antibody T lymphocytes - T Cell Receptor Each lymphocyte expresses only a SINGLE SPECIFICITY RECEPTOR

18 Diversity Human genome has ~30,000 protein encoding genes Exposure to unlimited number of antigens Humans have such a large immune repertoire. How? by G.O.D

19 Generation of Diversity (G.O.D): BCR and TCR Multiple germ-line gene segments (Inherited diversity) Combinatorial V-(D)-J joining TCR Junctional flexibility Combinatorial association of light and heavy chains Somatic hypermutation BCR Class-switch recombination

20 Combinatorial antibody diversity in humans The potential number of immune receptors is around ~ 10 12

21 Self/non-self discrimination: The Clonal selection

22 Immunologic memory The attribute of the adaptive immune system mediated by MEMORY CELLS where by second encounter with same antigen results in heightened state of immune reactivity

23

24

25 Innate immunity and Adaptive immunity collaborate to protect the body

26 Adaptive Immune System Antigenic Specificity Diversity Memory response Self/non-self discrimination

27 Thank You

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