Chapter 7: Adaptive Immunity

Question 1

Overview of Adaptive Immunity

Answer 1

1. 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.
2. 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.
3. 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.
4. Adaptive immunity can be either active or passive depending on whether immune response components originated in the host or came from a donor.
5. B and T lymphocytes leaving the primary lymphoid organs are immunocompetent but have not been exposed to antigen, thus are naïve.
6. Clonal selection is initiated when exposure to an antigen occurs.

Question 2

Antigens and Immunogens

Answer 2

1. Antigens are molecules that bind and 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 these antigens are called immunogens.
2. All immunogens are antigens, but not all antigens are immunogens.
3. Some pathogens are successful because they mimic “self” antigens but avoid inducing an immune response.
4. Common antigens include infectious agents, allergens, chemical agents, and abnormal molecules on the surface of cells.
5. Large molecules, such as proteins, polysaccharides, and nucleic acids, are most immunogenic. Thus molecular size is an important factor for antigen immunogenicity.
6. Haptens are antigens too small to be immunogens by themselves but become immunogenic after combining with larger molecules.
7. The antigenic determinant, or epitope, is the precise chemical structure with which an antibody or B-cell/T-cell receptor (BCR/TCR) reacts.
8. 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.

Question 3

Immune Response: Collaboration of B Cells and T Cells

Answer 3

1. The generation of clonal diversity results in production of B and T lymphocytes with receptors against millions of antigens that possibly will be encountered in an individual’s lifetime occurs in the fetus in the primary lymphoid organs: the thymus for T cells and portions of bone marrow for B cells..
2. The generation of clonal diversity is the differentiation of lymphoid stem cells into B and T lymphocytes. Lymphoid stem cells interact with stromal cells through a variety of adhesion factors. As the stem cell matures it develops a variety of surface markers or receptors, one of the earliest is interleukin-7 (IL-7) receptor. IL-7, produced by stromal cells is critical for driving differentiation and proliferation of the B cell.
3. The next stage in development is formation of the BCR. The role of the BCR is to recognize antigen and communicate that information to the cell’s nucleus.
4. The enormous repertoire of BCR specificities is made possible by rearrangement of existing deoxyribonucleic acid (DNA) during B-cell development in the primary lymphoid organs, a process called somatic recombination.
5. Somatic rearrangement of the antibody variable regions will frequently result in a BCR that recognizes the individual’s own antigens, which may result in attack on “self” antigens expressed on various tissue and organs. Many of these “autoreactive” B cells are eliminated in the bone marrow. Most of the developing B cells undergo apoptosis. This entire process is referred to as clonal deletion or central tolerance.
6. The process of T-cell proliferation and differentiation is similar to that for B cells. The primary lymphoid organ for T-cell development is the thymus. Lymphoid stem cells travel through the thymus, where thymic hormones and the cytokine IL-7 promote lymphoid stem cell division and the production of receptors. They exit the thymus as mature immunocompetent T cells with antigen-specific receptors on the cell surface.
7. TCR proceeds in a manner similar to BCR. Initially proteins called CD4 and CD8 are expressed on the developing cells. As the cell matures they retain either the CD4 molecule or the CD8 molecule but not both. Eventually CD4 cells develop into T-helper cells (Th cells) and CD 8 cells become T-cytotoxic cells (Tc cells). Other mature T cells include T-regulatory cells (Treg cells) and memory cells.
8. The generation of clonal diversity concludes when immunocompetent T and B cells migrate from the primary lymphoid organs into the circulation and secondary lymphoid organs to await antigen.
9. The induction of an immune response, or clonal selection, begins when antigen enters the individual’s body.
10. Most antigens must first interact with antigen-presenting cells (APCs) (e.g., dendritic cells, macrophages, and B cells).
11. To induce an optimal cellular or humoral immune response, APCs must present antigens to Th cells. Antigen is processed in the APCs and presented on the cell surface by molecules of the major histocompatibility complex (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. MHC class II molecules are found only on APCs. Tc cells require that the antigen be presented by MHC class I molecules.
12. The T cell sees the presented antigen through the TCR 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.
13. Th cells consist of Th1 cells, which help Tc cells respond to antigen; Th2 cells, which help B cells develop into plasma cells; and Th17 cells, which help activate macrophages.
14. Tc cells bind to and kill cellular targets, such as cells infected with viruses or cancer cells.
15. 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.

Question 4

Humoral Immunity (Antibodies)

Answer 4

1. The humoral immune response consists of molecules (antibodies) produced by B cells. B cells are lymphocytes.
2. Antibodies are plasma glycoproteins that can be classified by chemical structure and biologic activity as immunoglobulin G (IgG), IgM, IgA, IgE, or IgD.
3. A typical antibody molecule is constructed of two identical heavy chains and two identical light chains (either κ or λ) and has two Fab portions that bind antigen and an Fc portion that interacts with complement or receptors on cells.
4. The protective effects of antibodies may be direct through the action of antibody alone or indirect requiring activation of other components of the innate immune response.
5. IgE is a special class of antibody produced against environmental antigens that are the primary cause of common allergies. It also protects the individual from infection by large parasitic worms (helminths).
6. The secretory immune system protects the external surfaces of the body through secretion of antibodies in bodily secretions, such as tears, sweat, saliva, mucus, and breast milk. IgA is the dominant secretory immunoglobulin.

Question 5

Cell-Mediated Immunity

Answer 5

1. Other effector T cells include Tc cells that attack and destroy cells expressing antigens from intracellular origins, Treg cells that suppress the immune response, and T lymphokine–producing cells that secrete cytokines that activate other cells.
2. Tc cells are responsible for cell-mediated destruction of abnormal cells, such as tumor cells or cells infected with viruses.
3. Attachment to a target cell activates multiple killing mechanisms through which the Tc cell induces the target cell to undergo apoptosis.
4. Two subsets of Th cells amplify inflammation. Th1 cells, in addition to assisting Tc-cell clonal selection, secrete cytokines that activate M1 macrophages to increase phagocytic and microbial killing functions. Th2 cells, in addition to assisting B-cell clonal selection, secrete cytokines that activate M2 macrophages for healing and repair of damaged tissue.
5. Th17 cells secrete a set of cytokines that recruit phagocytic cells to a site of inflammation. Th17-cell cytokines also activate epithelial cells to produce antimicrobial proteins in defense against certain bacterial and fungal pathogens.
6. Treg cells are a diverse group of T cells that control the immune response, usually suppressing the response and maintaining tolerance against self antigens. Treg cells produce very high levels of immunosuppressive cytokines, which decrease Th1 and Th2 activity by suppressing antigen recognition and Th-cell proliferation.

Question 6

Pediatric Considerations: Age-Related Factors Affecting
Mechanisms of Self-Defense in the Newborn Child

Answer 6

1. Neonates often have transiently depressed inflammatory function, particularly neutrophil chemotaxis and alternative complement pathway activity.
2. 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.
3. 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.

Question 7

Geriatric Considerations: Age-Related Factors Affecting Mechanisms
of Self-Defense in the Elderly

Answer 7

1. Elderly persons are at risk for impaired wound healing, usually because of chronic illnesses.
2. 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).