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Specific Defenses of the Host Part 1 (acquired or adaptive immunity) Specific Defenses of the Host Also called acquired or adaptive immunity. Although one is born with the ability to respond to foreign invasion of the body, the specific response is developed during a person’s lifetime. Immunity, unlike resistance, involves the production of a specific defensive response against the foreign organisms or substances that have invaded the body. The immune system contains two components the humoral arm of the immune system involves antibodies (also called immunoglobulins) that are dissolved in blood and lymph Antibodies are produced by B lymphocytes upon exposure to a foreign antigen (an antigen is anything that can stimulate a specific immune response) The Structure of a Monomeric Antibody Immune system, continued B cells have antibodies on their cell surface and the antibody acts as a surface receptor for the antigen. The antibody actually recognizes only a small region of the antigen called the antigenic determinant. Each antigen has many different antigenic determinants. Antigenic determinants Immune system, continued Each B cell has many identical antibodies on its surface. The specificity of each antibody on the surface of a single B cell is the same. In other words, all of the antibodies on the surface of a single B cell recognize the same antigenic determinant. After binding of the antigen (specifically, the antigenic determinant) to the antibody on the B cell surface, the B cell is stimulated to produce and secrete antibody of the same specificity that was on the surface of the B cell. Antigens and B cell receptors Secretion of antibody following B lymphocyte stimulation B cell clonal expansion Immune System, continued Therefore, the B cells produces antibody that will specifically react with the antigen (specifically, the antigenic determinant) that stimulated its production. Antibodies (or B cell receptors) can recognize and bind to linear proteins, folded proteins (may recognize non-linear sequences), polysaccharides, or nucleic acids. Linear Versus Non-linear Antigenic Determinants Immune System, continued The second arm of the immune system is called the cell mediated arm of the immune system. Involves T lymphocytes that are found in blood and lymphoid tissues. T cells, like B cells, have receptors on their cell surface (called the T cell receptor) that recognize and bind to antigens (or, more specifically, antigenic determinants). The T cell receptor is similar in structure to an antibody. Structure of the T cell receptor Immune System, continued All of the T cell receptors on the surface of a single T cell recognize the same antigenic determinant. The T cell receptor is capable of recognizing only antigenic determinants that are linear pieces of proteins (peptides). The significance of this will become clear later in the lecture. After binding of the T cell receptor with its specific antigenic determinant, the T cell will be stimulated to differentiate into an effector cell. There are several different types of effector cells (helper, supressor, cytotoxic, etc.) Effector T cells T4 activation T4 proliferation T8 activation Killing by cytotoxic T cell Mechanisms of the Immune Response Both B and T cells have an antigen independent and an antigen dependent phase of maturation. Antigen independent maturation Pluripotential stems cells in the bone marrow produce immature B cells that mature to immunocompetent B cells in the bone marrow. Immunocompetent B cells have antibody receptors on their surface and are capable of functioning in an immune reaction. Mechanisms of the Immune Response, continued Plurpotential stem cells in the bone marrow produce immature T cells that move to the thymus where they mature into immunocompetent T cells which have T cell receptors on their surface that are capable of interacting with an antigenic determinant in an immune response. In the thymus the T cells learn to distinguish between self-antigens and non-self antigens. Thus, the immune system does not normally produce a specific immune response against self-antigens. Antigen independent maturation Mechanisms of the Immune Response, continued Antigen dependent maturation Antigen dependent maturation begins when antigen (antigenic determinant) binds to an antibody receptor on the surface of a B cell or the T cell receptor on the surface of a T cell. Binding of the antigen will stimulate a clonal expansion (proliferation) and differentiation of the B or T cell. B cells will differentiate either into plasma cells that will secrete antibody of the same specificity (recognizes the same antigenic determinant) that was on the surface of the original B cell or into memory B cells. Antigen dependent maturation of B cells B cell clonal expansion Mechanisms of the Immune Response, continued T cells will differentiate either into an effector cell (helper, supressor, cytotoxic, etc) or into a memory cell. Memory cells are responsible for the anamnestic or secondary response that occurs the next or subsequent times that the same antigen is encountered. The anamnestic response is usually much quicker or stronger than the primary or original response. Antigen dependent maturation of T cells Mechanisms of the Immune Response, continued B cells often work together with T cells and macrophages during an immune response. When an antigen comes in, B cells and macrophages will process the antigen and present pieces of it (antigenic determinants) to the B or T cell for stimulation. Mechanisms of the Immune Response, continued Mechanisms of the Immune Response, continued Many antigens require T cell interaction for B cell stimulation and production of secreted antibodies. T dependent antigens require T help (T helper cells) for B cell stimulation. T dependent antigens are all protein antigens that contain some epitopes recognized by T cells and other epitopes recognized by B cells. Stimulation of the B cell requires two signals. One signal comes from the binding of the antigen itself to the B cell receptor (antibody). The second signal comes from an interaction of the B cell with a T cell. Mechanisms of the Immune Response, T Dependent Antigens < 1/100,000 of any individual’s immunocompetent lymphocytes are specific for any one antigen Mechanisms of the Immune Response, T Dependent Antigens Some definitions for previous slide IgM, IgG Isotype switching – Also known as “heavy chain class switching” A step in B cell maturation Each of the different heavy chain types is optimal for eliminating certain types of microbes. Affinity maturation 2 of 5 different isotypes, M,G,A,D,E Isotypes differ with respect to the form of the heavy chain. A step in B cell maturation that occurs in the germinal centers of the lymph nodes. Isotype switching also occurs in cells that undergo affinity maturation. Memory cells may be derived either before or after affinity maturation. Mechanisms of the Immune Response, continued T helper cells have CD4 on their cell surfaces. The significance of this will be explained later. The T helper cell must be armed by previous exposure to the same antigen as the B cell which it helps. The T cell is restricted in that it can only help B cells produced by the same individual that produced the T cells. This is because the T cell can only recognize the foreign antigen in the context of a self-antigen (an MHC complex). Mechanisms of the Immune Response, T Dependent Antigens Note that the B cell surface antibody recognizes one epitope of the antigen while the helper T cell recognizes another epitope in the context of an MHC Class II molecule. The antigen is the same (even though it doesn’t look like it), but the epitopes differ. In the B cell, some crosslinking of membrane bound antibodies must occur. B-T interaction B-T interaction Mechanisms of the Immune Response, continued T independent antigens don’t require T help for B cell stimulation. T independent antigens are usually in the form of a repeating subunit like a polysaccharide, lipid, or nucleic acid. Binding by this type of antigen somehow provides both signals that are required for B cell stimulation (by causing extensive cross-linking the surface antibodies?) The outcome from this type of stimulation is clearly different from that which occurs in T-dependent stimulation, since with the T-independent stimulation no memory cells are made. There is no anamnestic response for T-independent antigens. T-independent activation of B cells How does the response differ from Tdependent activation? Compare with slide #32. Mechanisms of the Immune Response, continued Cytotoxic T lymphocytes (CTLs) have CD8 on their surfaces (significance will be described later) and they act to destroy target cells, including infected cells, cancer cells, and tissue transplants. Cytotoxic T cells are like T helper cells in that, in order to function, they can only recognize a foreign antigen in the context of a self-antigen (MHC complex). The T cell restriction (for both T helper cells and cytotoxic T cells) involves proteins (sometimes called antigens) encoded in the Major Histocompatibility Complex (MHC).