General Microbiology (Micr300) Lecture 15 Adaptive Immunity (Text Chapter: 22.5-22.11)

Lymphocytes: The Cellular Arms of Adaptive Immunity T-lymphocytes Mature in thymus Interact with other defense cells (T helper cells, TH) or kill abnormal cells (cytotoxic T cells, Tc) B-lymphocytes Mature in bone marrow Produce antibodies

The Adaptive Immune Response In adaptive immunity, phagocytes present antigen to specific T cells, triggering the proliferation of effector T cells and subsequently the production of antibodies. Immune T cells and antibodies attack directly or indirectly the antigen. The adaptive immune response is characterized by specificity for the antigen, the ability to respond more vigorously when reexposed to the same antigen (memory), and the ability to discriminate self antigens from nonself antigens (tolerance) (Figure 22.8).

Specific Interactions

Memory

Tolerance

Immunogens Immunogens are foreign macromolecules that induce an immune response. Molecular size, complexity, and physical form are intrinsic properties of immunogens. Molecular size is an important component of immunogenicity. For example, low-molecular-weight compounds called haptens cannot induce an immune response but can bind to antibodies. Because haptens are bound by antibodies, they are antigens even though they are not immunogenic.

Structure of the T-cell Receptor (TCR)

Antigenic Determinants

Epitope The antibody or TCR does not interact with the antigenic macromolecule as a whole but only against a distinct portion of the molecule called an antigenic determinant or epitope.

Presentation of Antigen to T Lymphocytes T cells recognize digested antigens presented by antigen-presenting cells (APCs) or by pathogen-infected cells. At the molecular level, TCRs bind peptide antigens presented by major histocompatibility complex (MHC) proteins. Class I MHC proteins are found on the surfaces of all nucleated cells. Class II MHC proteins are found only on the surface of B lymphocytes, macrophages, and dendritic cells, all of which are APCs (Figure 22.11).

Class I MHC Class II MHC

T-Cytotoxic Cells and Natural Killer Cells T-cytotoxic (TC) cells recognize antigens presented via MHC I on virus-infected host cells and tumor cells through antigen-specific TCRs. Antigen-specific recognition triggers killing via perforin and granzymes (Figure 22.13). TC use a special molecule called CD8 to dock onto MHC I.

T-Cytotoxic Cells

T-Helper Cells T helper cells secrete cytokines to direct the function of other immune cells. Depending on the cytokine profile T helper cells are dived into subgroups TH1 cells enhance phagocyte function in destroying pathogens and promote inflammation TH2 cells stimulate B cells to proliferate, augment antibody production and develop into plasma cells (Figure 22.14).

T-Helper Cells Pro-inflammatory cytokines

T cell – B cell Interaction Antibody inducing cytokines T cell – B cell Interaction

Antibodies (Immunoglobulins) Immunoglobulin (Ig) (antibody) proteins consist of four chains, two heavy and two light (Figure 22.15). Each chain consists of different domains. The amino-terminal region is a variable domain, meaning that the amino acid sequence in this structural region differs in each different antibody. The antigen-binding site is formed by the interaction of variable regions of heavy and light chains. The constant regions are very uniform among groups of antibodies There are 5 major groups of antibodies (isotypes) that differ in the make up of their constant region of the heavy chain (IgG, IgM, IgA, IgD, IgE)

Immunoglobulin G Structure Fab (antigen-binding fragment) Fc (constant fragment) L: light chain H: heavy chain

The Antigen Binding Groove: Lock-Key Principle

Antibody Isotypes IgG IgM IgA IgD IgE g m a d e Isotype Heavy chain type g m a d e Main function Phagocytosis AgglutinationComplement activation Placenta-transfer Neutralization Agglutination Complement activation Mucosal protection ? B cell maturation marker Allergies

Effector Functions of Antibodies Neutralization (blocking) Opsonization (enhancing phagocytosis) Complement Activation (direct killing, enhancing phagocytosis)

Antibody Production Antibody production is initiated by antigen contact with an antigen-specific B cell and is always IgM (Primary antibody response) B cells require support from T helper cells for full production of antibodies including other isotypes B cells take up and process antigen, present it to T helper cells, which in turn secrete cytokines to signal large scale production and isotype switch

Antibody Production Some activated B cells develop into plasma cells and produce and secrete large amounts of antibody of isotypes other than IgM Some activated B cells develop into long living memory cells and can rapidly produce large quantities (high titers) of antibodies upon reexposure to antigen (secondary antibody response, Figure 22.21). Memory B cells do not need T cell activation

Primary & Secondary Antibody Responses

Antibodies As Tool Inject antigen into rabbit (with immune stimulator = adjuvant) Re-inject for 2 or 3 times Rabbit will make antibodies against the antigen Draw blood, prepare serum = polyclonal antibodies

Antibodies in Immunoassays: ELISA