| Foundations in Microbiology, 4/e Kathleen Park Talaro,
Pasadena City College Arthur Talaro
The Acquisition of Specific Immunity and Its Applications
Chapter Capsule I. Development of Lymphocyte Specificity/Receptors
A. Acquired immunity involves the reactions of B and T lymphocytes to foreign molecules, or antigens. Before they can react, each lymphocyte must undergo differentiation into its final functional type by developing protein receptors for antigen, the specificity of which is genetically controlled and unique for each type of lymphocyte. B. The clonal selection theory explains this process. Genetic recombination and mutation during embryonic and fetal development produce billions of different lymphocyte clones, each bearing a different receptor. This provides a huge lymphocyte repertoire required to react with antigens. C. Tolerance to self, the elimination of any lymphocyte clones that can attack self, occurs during this time. D. The receptors on B cells are immunoglobulin (Ig) molecules, and receptors on T cells are smaller glycoprotein molecules. E. Other receptors needed in recognition are governed by the major histocompatibility (MHC) gene complex, which is also referred to as the human leukocyte antigen (HLA) complex. F. Expression of these genes gives rise to receptors on most cells that govern cell communication and recognition of self and antigens. G. B-Cell Maturation: Immature B stem cells originate in the yolk sac, liver, and bone marrow and differentiate into mature cells under the influence of special stromal cells in the bone marrow. Mature cells acquire Ig receptors and home to predetermined sites in lymphoid organs, ready to react with antigen. H. T-Cell Maturation: Immature T stem cells originate in the same areas of the embryo and fetus but mature under the influence of the thymus gland. Specificity is acquired through addition of
CD receptors, and mature cells home to different sites in lymphoid organs. II. Introduction of Antigens/Immunogens
A. An antigen (Ag) is any substance that stimulates an immune response.
1. Requirements for antigenicity include foreignness (recognition as nonself), large size, and complexity of cell or molecule. 2. Foreign cells and large complex molecules (over 10,000 MW) are most antigenic. 3. Foreign molecules less than 1,000 MW (haptens) are not antigenic unless attached to a larger carrier molecule. 4. The antigenic determinant is the small molecular group of the foreign substance that is recognized by lymphocytes. Cells, viruses, and large molecules can have numerous antigenic determinants. B. Special categories of antigens include:
1. Autoantigens, molecules on self tissues for which tolerance is inadequate. 2. Alloantigens, cell surface markers of one individual that are antigens to another of that same species. 3. Heterophilic antigens, molecules from unrelated species that bear similar antigenic determinants. 4. Superantigens, complex bacterial toxins. 5. Allergen, the antigen that provokes allergy. III. Cooperation in Immune Reactions to Antigen
A. T-cell-dependent antigens must be processed by special macrophages, the antigen-processing cells (APCs). An APC alters the antigen and attaches it to its MHC receptor for presentation to lymphocytes. B. Antigen presentation involves a direct collaboration among the macrophage, a T helper (TH) cell, and an antigen-specific B or
T cell. C. Cytokines involved are Interleukin-1 from the APC which activates the TH cells, and interleukin-2 produced by the TH cell, which activates B and other T cells. IV. B-Cell Activation and Antibody Production
A. When B cells receive the antigen and are stimulated by B-cell growth and differentiation factors, they enter the cell cycle in preparation for mitosis and clonal expansion. B. Divisions give rise to plasma cells that secrete antibodies and memory cells that can react to that same antigen later.
1. Nature of Antibodies (Immunoglobulins): A single immunoglobulin molecule (monomer) is a large Y-shaped protein molecule consisting of four polypeptide chains. It contains two identical fragments (Fab) with ends that form the active site that binds with a unique specificity to an antigen. The single fragment of the antibody (Fc) binds to self. 2. Antigen-Antibody (Ag-Ab) Reactions include opsonization, neutralization by antitoxin, agglutination, and complement fixation.
a. The Fc portion can bind to various body cells and mediate inflammation and allergy. 3. The five antibody classes, which differ in size and function, are IgG, IgA (secretory Ab), IgM, IgD, and IgE. 4. Antibodies in Serum (Antiserum):
a. Serum antibodies can be identified through electrophoresis and quantified by testing the titer (levels of antibodies) over time. b. The first introduction of an Ag to the immune system produces a primary response, with a gradual increase in Ab titer. c. The second contact with the same Ag produces a secondary, or anamnestic, response, due to memory cells produced during initial response. 5. Monoclonal antibodies (MAB) are single specificity antibodies formed by fusing a mouse B cell with a cancer cell. MABs are used in diagnosis of disease, identification of microbes, and therapy. V. T Cells and Cell-Mediated Immunity (CMI)
A. T cells act directly against antigens and foreign cells. T cells secrete cytokines (interleukin, interferon, lymphotoxins) that act on other cells. Sensitized T cells proliferate into long-lasting memory T cells and one of the following depending upon its
CD receptor:
1. T helper cells (TH) assist other T cells and B cells. 2. T suppressor cells (TS) limit the actions of other T cells and B cells. 3. Cytotoxic, or killer, T cells (TC) destroy complex foreign or abnormal cells by forming perforins that lyse the cell. 4. Delayed hypersensitivity cells (TD) cause a form of hypersensitivity. VI. Classification of Acquired Immunity
A. Immunities acquired through B and T lymphocytes can be classified by a simple system.
1. Natural immunity is acquired as part of normal life experiences. 2. Artificial immunity is acquired through medical procedures such as immunization. 3. Active immunity results when a person is challenged with antigen that stimulates production of antibodies. It creates memory, takes time, and is lasting. 4. In passive immunity, preformed antibodies are donated to an individual. It does not create memory, acts immediately, and is short term. B. Combinations of acquired immunity are:
1. Natural active, acquired upon infection and recovery, and natural passive, acquired by a child through placenta and breast milk. 2. Artificial active (vaccination), acquired through inoculation with a selected antigen, and artificial passive, administration of immune serum or globulin.
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