Specific Resistance = Immunity Immunology = study of a host’s specific defenses, i.e. immunity. Lymphocytes (review) Antigens & Antibodies Acquired Immunity Humoral Immunity: B-cell Function Cell-Mediated Immunity: T-cell Function

Lymphocyte 100 million produced per day therefore others must die (apoptosis = programmed cell death) B cells: Interact with antigens; may develop a clonal population of memory cells or become stimulated, divide and mature into antibody producing plasma cells. Antibody functions are called Humoral Immunity. T cells: Act as either “helpers” in communicating the presence of an antigen; or cytotoxic agents to destroy infected cells. These functions are called Cell-Mediated Immunity.

Antibody Monomer Structure: Many possible antibodies with different antigenic binding sites due to variable region diversity of long and short chains. Immunoglobin (Ig) = antibody

Antigen-Antibody Interaction Antigen = a substance with unique 3D form that causes antibody formation in B cells (lymphocytes). Antigens may possess one or more types of reactive molecular components, called antigenic determinants or epitopes. Antigen binding sites on the antibody Fab fragments specifically recognize and chemically interact with an epitope. Because a single antibody recognizes a single epitope, there may be multiple antibodies generated against an antigen with more than one epitope.

Antigens can be pieces of or whole microbes or viruses. i.e. epitopes

Antigens can be derived from very small molecules called haptens, which without some carrier molecule or cell would not elicit an immune response alone. Examples of haptens include drugs and/or toxins (e.g. some venoms). Think of a heptan as functioning as the epitope for an incomplete antigen (carrier molecule).

Antibody Classes IgG (80%; monomer; passive to fetus/newborn); IgM (<10%, pentamer of IgG, effective in agglutination); IgA (< 15%; dimer; on B cell surface involved in activation; released into fluid/mucus secretions); IgD (minor; monomer; on B cell surface involved in their activation); and IgE (minor; monomer; on mast cells and basophils; involved in allergic response).

vaccine antiserum Passive = antibodies supplied to host from external sources, possibly prior to the presence of any foreign antigen in the host. Active = Foreign antigen introduced to host, which then stimulates immune response.

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)

T-independent versus T-dependent Antigens Antigens fall into one of two broad types! (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

Immune complex forms:

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.

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.

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 for binding to class I–MHC on infected hosts.

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.

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.

Immunity Overview