Monday, July 2, 2007

ACQUIRED (SPECIFIC) IMMUNITY

Acquired or specific immunity reflects the presence of a functional immune system that is capable of specifically recognizing and selectively eliminating foreign microorganisms and molecules (i.e., foreign antigens). Unlike innate immune responses, acquired immune responses are adaptive and display four characteristic attributes:
• Antigen specificity
• Diversity
• Immunological memory
• Self/nonself recognition
The antigen specificity of the immune system permits it to distinguish subtle (exact) differences among antigens. The immune system is capable of generating tremendous diversity in its recognition molecules, allowing it to specifically recognize billions of uniquely different structures on foreign antigens. Once the immune system has recognized and responded to an antigen, it exhibits immunologic memory; that is, a second encounter with the same antigen induces a heightened state of immune reactivity. Finally, the immune system normally responds only to foreign antigens indicating that it is capable of self/nonself recognition. The ability of the immune system to distinguish self from nonself and respond only to nonself-molecules is essential, for the outcome of an inappropriate response to self-molecules can be a fatal autoimmune disease.

Cells of Immune System:
Generation of an effective immune response involves two major groups of cells; lymphocytes and antigen presenting cells. Lymphocytes are one of many types of white blood cells produced in the bone marrow during the process of hematopoiesis. Lymphocytes leave the bone marrow circulate in the blood and lymph system, and reside in various lymphoid organs. Lymphocytes, which possess antigen-binding cell-surface receptors, possess the defining immunologic attributes of specificity, diversity, memory, and self/nonself recognition. The two major populations of lymphocytes are: B – lymphocytes (B cells) and T – Lymphocytes (T cells)

B Lymphocytes
B-lymphocytes mature within the bone marrow and leave the marrow expressing a unique antigen-binding receptor on their membrane. The B – Lymphocyte receptor is a membrane-bound antibody molecule. Antibodies are glycoproteins. The basic structure of the antibody molecule consists of two identical light polypeptide chains. The chains are held together by disulfide bonds. The amino-terminal ends of each pair of heavy and light chains form a cleft within which antigen binds. When a naïve B cell, which has not previously encountered antigen, first encounters the antigen for which its membrane bound antibody is specific, the cell begins to divide rapidly; its progeny differentiate into memory B cells and effector B cells called plasma cells.
Memory B cells have a longer life span and continue to express membrane-bound antibody with the same specificity as the original parent naïve B cell. Plasma cells do not express membrane-bound antibody; instead they produce the antibody in a form that can be secreted. Although plasma cells live for only a few days, they secrete enormous amounts of antibody during the time.
T Lymphocytes:
T lymphocytes also arise from hematopoietic stem cells in the bone marrow. Unlike B cells, which mature within the bone marrow, T cells migrate to the thymus gland to mature. During its maturation within the thymus, the T cell comes to express a unique antigen-binding receptor on its membrane, called the T-Cell receptor. Unlike membrane-bound antibodies on B cells, which can recognize antigen alone, T cell receptors can only recognize antigen that is associated with cell-membrane proteins known as major histocompatibility complex (MHC) molecules. When a naïve T cell encounters antigen associated with a MHC molecule on a cell, the T cell proliferates and differentiates into memory T cell and various effector T cells.
There are two well-defined subpopulation of T cells - T helper (TH) and T cytotoxic (TC) cells. After a TH cell recognizes and interacts with an antigen-MHC molecule complex, the cell is activated and becomes an effector cell that secretes various growth factors know collectively as cytokines. Under the influence of TH -derived cytokines, a TC cell that recognizes an antigen-MHC complex proliferates and differentiates into an effector cell called a cytotoxic T Lymphocyte.

Functions of Humoral and Cell-Mediated Immune Responses:

Immune responses can be divided into humoral and cell-mediated responses.
The term humoral is derived from the Latin humor, meaning “body fluid”; thus humoral immune system involves interaction of B cells with antigen and their subsequent proliferation and differentiation into antibodies. Antibody functions as the effector of the humoral response by binding to antigen and neutralizing it or facilitating its elimination. When an antigen is coated with antibody, it can be eliminated in several ways. For example, antibody can cross-link the antigen, forming clusters that are more readily ingested by phagocytic cells. Binding of antibody to antigen on a microorganism also can activate the complement system, resulting in lysis of the foreign organism. Antibody can also neutralize toxins or viral particles by coating them and preventing their subsequent binding to host cells.

Effector T cells generated in response to antigen are responsible for cell-mediated immunity. Activated TH cells serve as effector cells in cell-mediated immune reactions. Cytokines secreted by TH cells can activate various phagocytic cells, enabling them to phagocytose and kill microorganisms more effectively. This type of cell-mediated immune response is especially important in host defense against intracellular bacteria and protozoa. Cytotoxic T lymphocytes (CTLs) participate in the cell-mediated immune reactions by killing altered self-cells; they play an important role in the killing of virus-infected cells and tumor cells.

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