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General Characteristics of the Immune Response
- Adaptive immunity is a state of protection, primarily against infectious agents, that differs from inflammation by being slower to develop, being more specific, and having memory that makes it much longer lived.
- Natural immunity is innate resistance, and acquired immunity is gained after birth.
- The adaptive immune response is most often initiated by cells of the innate system. These cells process and present portions of invading pathogens (i.e., antigens) to lymphocytes in peripheral lymphoid tissue.
- The adaptive immune response is mediated by two different types of lymphocytes—B lymphocytes and T lymphocytes. Each has distinct functions. B cells are responsible for humoral immunity that is mediated by circulating antibodies, whereas T cells are responsible for cell-mediated immunity, in which they kill targets directly or stimulate the activity of other leukocytes.
- Adaptive immunity can be either active or passive depending on whether immune response components originated in the host or came from a donor.
Antigens and Immunogens
- Antigens are molecules that react with components of the immune response, such as antibodies and receptors on B and T cells. Most antigens can induce an immune response, and this the antigens are also immunogens.
- The antigenic-determinant or epitope is the precise chemical structure with which an antibody or B cell/T cell receptor reacts.
- Self-antigens are antigens on an individual’s own cells. The individual’s immune system does not normally recognize self-antigens as immunogenic, a condition known as tolerance.
- Very small antigens may not normally be immunogenic (haptens) unless they are bound to a larger molecular weight molecule (carrier).
Humoral Immune Response
- The humoral immune response is provided by molecules (antibodies) produced by B cells.
- Antibodies are plasma glycoproteins that can be classified by chemical structure and biologic activity as IgG, IgM, IgA, IgE, or IgD.
- The protective effects of antibodies may be direct or indirect.
- Direct effects result from the binding of antibody directly to a harmful antigen or infectious agent. These include inhibition of processes that are necessary for infection, such as the reaction of an infectious agent with a particular cell in the body or neutralization of harmful bacterial toxins.
- Indirect effects result from activation of inflammation by antibodies through the Fc portion of the molecule. These include opsonization to increase phagocytosis, killing the infectious agent through activation of complement, and widespread activation of inflammation through the production of biologically active complement components, such as C5a.
- IgE is a special class of antibody that helps defend against parasitic infections.
- Antibodies of the systemic immune system function internally, in the bloodstream and tissues. Antibodies of the secretory, or mucosal, immune system (primarily secretory IgA) function externally, in the secretions of mucous membranes.
Cell-Mediated Immune Response
- T cells are responsible for the cell-mediated immune response.
- There are several types of mature T cells: cytotoxic T cells (Tc), regulatory T cells including T helper (Th), and T suppression (Ts), and memory cells.
- T cells have antigen specific receptors (T cell receptor or TCR) that must “see” antigen presented on cell surfaces by special antigen-presenting molecules of the major histocompatibility complex (MHC molecules).
- Tc cells bind to and kill cellular targets such as cells infected with viruses or cancer cells.
- The natural killer (NK) cell has some characteristics of the Tc cells and is important for killing target cells in which viral infection or malignancy has resulted in the loss of cellular MHC molecules.
- Development of cell-mediated or humoral immune responses usually depends on populations of Th cells.
Generation of Clonal Diversity
- The production of B and T lymphocytes with receptors against millions of antigens that will be possibly encountered in an individual’s lifetime occurs in the fetus in the primary lymphoid organs: the thymus for T cells and portions of the bone marrow for B cells.
- Immunocompetent T and B cells migrate from the primary lymphoid organs into the circulation and secondary lymphoid organs to await antigen.
Induction of the Immune Response
- Induction of an immune response, or clonal selection, begins when antigen enters the individual’s body.
- The response to antigen can be divided into two phases: the primary and secondary responses. The primary response of humoral immunity is usually dominated by IgM, with lesser amounts of IgG. The secondary immune response has a more rapid production of a larger amount of antibody, predominantly IgG.
- Most antigens must first interact with antigen-presenting cells (APCs), i.e., macrophages.
- Antigen is processed in the APCs and presented on the cell surface by molecules of the MHC. The particular MHC molecule (class I or class II) that presents antigen determines which cell will respond to that antigen. Th cells require that the antigen be presented in a complex with MHC class II molecules. Tc cells require that antigen be presented by MHC class I molecules.
- The T cell “sees” the presented antigen through the T cell receptor and accessory molecules: CD4 or CD8. CD4 is found on Th cells and reacts specifically with MHC class II. CD8 is found on Tc cells and reacts specifically with MHC class I.
- A subgroup of Th cells (the Th2 cells) helps B cells respond to antigen and develop into antibody-secreting plasma cells.
- A second subgroup of Th cells (the Th1 cells) helps Tc cells respond to antigen and develop into functional effector Tc cells.
Pediatrics & Immune Function
- Mechanisms of self-defense are naturally somewhat deficient in the fetus, the neonate, and the elderly individual.
- The T cell-independent immune response is adequate in the fetus and neonate, but the T cell-dependent immune response develops slowly during the first 6 months of life.
- Maternal IgG antibodies are transported across the placenta into the fetal blood and protect the neonate for the first 6 months, after which they are replaced by the child’s own antibodies.
Aging & Immune Function
T cell function and antibody production are somewhat deficient in elderly persons. Elderly individuals also tend to have increased levels of circulating autoantibodies (antibodies against self-antigens).