Humoral Immunity: B Cells

1. Humoral Immunity: B Cells Each B cell produces a different IgD&M on its surface. Some antigens require involvement of helper T cells for B cell activation. Long-lived cells, stored in large numbers in lymph nodes; host is now “primed” for any second response by the same antigen. (particularly when stimulated by helper T cell’s interleukin-2)

2. Antigens fall into one of two broad types! T-independent versus T-dependent Antigens (Protein; polysaccharide; glycoprotein) • Antigens that are large multivalent polymers that bind multiple IgD&M on a B cell surface will directly stimulating humoral immunity independent of any helper T cell involvement. • Smaller protein antigens with too few epitopes for multiple IgD&M binding and direct stimulation of B cells will require involvement of helper T cells and there interleukins; they are dependent on T cells for stimulating humoral immunity. (see more below) B cell IgD & IgM

4. Immune complex forms:

5. ADCC: 1) Antibodies bind to parasite surface. 2) Fc region receptors on surface of eosinophils, macrophage and natural killer cells bind to antibody. 3) Release of cytokinins, perforins and other lytic enzymes to damage parasite tissues. 4) Liberation and /or phagocytosis of other parasite antigens to further activate immunity.

6. Cell-Mediated Immunity: T Cells • Helper T cells (TH) are needed to stimulate production of cytotoxic T cells (TC) and humoral immunity (B cells) to T-dependent antigens. • Important to this system is the ability for lymphocytes to distinguish normal host cells (“self”) from microbes or infected host cells. The major histocompatibility complex (MHC) on the surface of all host cells functions as a “self flag”. TH cell receptors (CD4+) bind to class II MHCs and Tc cell receptors (CD8+) to class I MHCs. • Events in cell-mediated immunity: • Antigen presenting cells (APC; macrophage and dendrites) phagocytize antigen carrying microbe, virus, or carrier molecule. 2) Antigen fragment with a unique epitope combines with the MHCs at the APC surface for presentation to helper T cells. Simultaneously, APC secrete IL-I. 3) A TH cell with a specific receptor for that epitope binds to the class II MHC on the APC, which together with IL-1 results in proliferation of that particular TH cell clonal population and secretion of other ILs.

7. Cell-Mediated Immunity: T Cells • The active clonal population of TH cells secretes IL-2 and other cytokinins. • These signals stimulate specific B cells to proliferate and mature to antibody secreting plasma cells (see details below for T-dependent antigens). • These signals also stimulate specific Tc cells to proliferate and activate. The Tc cells involved have their own receptors bound to class I - MHC.

8. The role of TH cells in humoral immunity to T-dependent antigens. • TH cell receptors unique to the epitope and MHC of concern may bind to B cells with complementary surface features. • These bound B cells are stimulated by IL-2 to proliferate and mature to plasma cells that secrete antibodies to the T-dependent antigen.

9. Cytotoxic T Cells: • They bind to infected target host cells (typically due to virus or intracellular bacterium) expressing the antigen-MHC via Tc cell receptor. They also bind to cells with non-self MHC (e.g. tranplants; tumor cells). • Binding stimulates secretion of extracellular enzymes (perforins) to degrade the target cell plasma membrane. • Grazymes (proteolytic enzymes) are released by Tc cells and enter infected cell through pores and induce apoptosis. • Rupturing of the membrane kills the target cell and releases Tc cell.

10. Immunity Overview

11. Stages of Disease Development Carrier? Carrier? Carrier? Susceptible to 2º infection

12. Carriers of Infectious Disease Causative agent is Salmonella typhi