BIOC 401 Immunochemistry Lecture Notes PDF

BIOC 401 Immunochemistry By Yasmene F. Alanazi CELLS OF THE IMMUNE SYSTEM  CELLS OF THE IMMUNE SYSTEM Lymphocytes circulate through lymphoid organs and nonlymphoid tissues. They recognize foreign antigens and initiate adaptive immune responses. Cells resident in tissues d...

BIOC 401 Immunochemistry By Yasmene F. Alanazi CELLS OF THE IMMUNE SYSTEM  CELLS OF THE IMMUNE SYSTEM Lymphocytes circulate through lymphoid organs and nonlymphoid tissues. They recognize foreign antigens and initiate adaptive immune responses. Cells resident in tissues detect the presence of microbes and react against them. These cells include macrophages, whose function is to ingest and destroy foreign substances; dendritic cells, which capture microbes and display them to lymphocytes to initiate immune responses, and are therefore called antigen presenting cells; and mast cells, which help to recruit other leukocytes to destroy microbes.  Cont. Phagocytes that normally circulate in the blood, including neutrophils and monocytes, are rapidly recruited to sites of infection in the process called inflammation. These leukocytes (white blood cells) ingest and destroy microbes and then start the process of repairing damaged tissues. Because these phagocytes, as well as some T lymphocytes, are responsible for the effect of the immune response, which is to destroy microbes, they are sometimes called effector cells.  Lymphocytes Lymphocytes are the only cells that produce clonally distributed receptors specific for diverse antigens and are the key mediators of adaptive immunity. B lymphocytes are the only cells capable of producing antibodies; therefore, they are the cells that mediate humoral immunity. B cells express membrane forms of antibodies that serve as the receptors that recognize antigens and initiate the process of activation of the cells. Soluble antigens and antigens on the surface of microbes and other cells may bind to these B lymphocyte antigen receptors, initiating the process of B cell activation. This leads to the secretion of soluble forms of antibodies with the same antigen specificity as the membrane receptors  Cont. classes of lymphocytes T lymphocytes are responsible for cell-mediated immunity. The antigen receptors of most T lymphocytes recognize only peptide fragments of protein antigens that are bound to specialized peptide display molecules, called major histocompatibility complex (MHC) molecules, on the surface of specialized cells, called antigen-presenting cells. Among T lymphocytes, CD4+ T cells are called helper T cells because they help B lymphocytes to produce antibodies and help phagocytes to destroy ingested microbes. CD8+ T lymphocytes are called cytotoxic T lymphocytes (CTLs) because they kill cells harboring intracellular microbes. Some CD4+ T cells belong to a special subset that functions to prevent or limit immune responses; these are called regulatory T lymphocytes.  Cont. All lymphocytes arise from stem cells in the bone marrow. B lymphocytes mature in the bone marrow, and T lymphocytes mature in an organ called the thymus. These sites in which mature lymphocytes are produced (generated) are called the generative lymphoid organs. Mature lymphocytes leave the generative lymphoid organs and enter the circulation and the peripheral lymphoid organs, where they may encounter antigen for which they express specific receptors. Maturation of lymphocytes. Lymphocytes develop from precursors in the generative lymphoid organs (bone marrow and thymus). Mature lymphocytes enter the peripheral lymphoid organs, where they respond to foreign antigens and recirculate in the blood and lymph. Some immature B cells leave the bone marrow and complete their maturation in the spleen. Classes of lymphocytes. Different classes of lymphocytes in the adaptive immune system recognize distinct types of antigens and differentiate into effector cells whose function is to eliminate the antigens. B lymphocytes recognize soluble or cell surface antigens and differentiate into antibody-secreting cells. Helper T lymphocytes recognize antigens on the surfaces of antigen-presenting cells and secrete cytokines, which stimulate different mechanisms of immunity and inflammation. Cytotoxic T lymphocytes recognize antigens in infected cells and kill these cells. (Note that T lymphocytes recognize peptides that are displayed by MHC molecules, discussed in Chapter 3.) Regulatory T cells limit the activation of other lymphocytes, especially of T cells, and prevent autoimmunity.  Cont. When naive lymphocytes recognize microbial antigens and also receive additional signals induced by microbes, the antigen-specific lymphocytes proliferate and differentiate into effector cells and memory cells  Cont. Naive lymphocytes express receptors for antigens but do not perform the functions that are required to eliminate antigens. These cells reside in and circulate between peripheral lymphoid organs and survive for several weeks or months, waiting to find and respond to antigen. If they are not activated by antigen, naive lymphocytes die by the process of apoptosis and are replaced by new cells that have arisen in the generative lymphoid organs. The differentiation of naive lymphocytes into effector cells and memory cells is initiated by antigen recognition, thus ensuring that the immune response that develops is specific for the antigen.  Cont. Effector lymphocytes are the differentiated progeny of naive cells that have the ability to produce molecules that function to eliminate antigens. The effector cells in the B lymphocyte lineage are antibody-secreting cells, called plasma cells. Plasma cells develop in response to antigenic stimulation in the peripheral lymphoid organs, where they may stay and produce antibodies. Small numbers of antibody-secreting cells are also found in the blood; these are called plasmablasts. Some of these migrate to the bone marrow, where they mature into long-lived plasma cells and continue to produce small amounts of antibody long after the infection is eradicated, providing immediate protection in case the infection recurs.  Cont. Effector CD4+ T cells (helper T cells) produce proteins called cytokines that activate B cells, macrophages, and other cell types, thereby mediating the helper function of this lineage. Effector CD8+ T cells (CTLs) have the machinery to kill infected host cells. Effector T lymphocytes are short-lived and die as the antigen is eliminated. Memory cells, also generated from the progeny of antigen-stimulated lymphocytes, do survive for long periods in the absence of antigen. Therefore, the frequency of memory cells increases with age, presumably because of exposure to environmental microbes. Memory cells are functionally inactive; they do not perform effector functions unless stimulated by antigen. When memory cells encounter the same antigen that induced their development, the cells rapidly respond to initiate secondary immune responses. The signals that generate and maintain memory cells are not well understood but include cytokines.  Antigen-Presenting Cells The common portals of entry for microbes—the skin, gastrointestinal tract, and respiratory tract—contain specialized antigen-presenting cells (APCs) located in the epithelium that capture antigens, transport them to peripheral lymphoid tissues, and display (present) them to lymphocytes. This function of antigen capture and presentation is best understood for a cell type that is called dendritic cells because of their long surface membrane processes. Dendritic cells capture protein antigens of microbes entering through the epithelia and transport the antigens to regional lymph nodes, where the antigen-bearing dendritic cells display portions of the antigens for recognition by T lymphocytes. If a microbe has invaded through the epithelium, it may be phagocytosed and presented by tissue macrophages. Microbes or their antigens that enter lymphoid organs may be captured by dendritic cells or macrophages that reside in these organs and presented to lymphocytes. Dendritic cells are the most effective APCs for initiating T cell responses.  Cont. Cells that are specialized to display antigens to T lymphocytes have another important feature that gives them the ability to stimulate T cell responses. These specialized cells respond to microbes by producing surface and secreted proteins that are required, together with antigen, to activate naive T lymphocytes to proliferate and differentiate into effector cells. Specialized cells that display antigens to T cells and provide additional activating signals sometimes are called professional APCs.