Summary

* The anatomic organization of the cells and tissues of the immune system is of critical importance for the generation of effective innate and adaptive immune responses. This organization permits the rapid delivery of innate effector cells, including neutrophils and monocytes, to sites of infection and permits a small number of lymphocytes specific for any one antigen to locate and respond effectively to that antigen regardless of where in the body the antigen is introduced.

* The cells that perform the majority of effector functions of innate and adaptive immunity are phagocytes (including neutrophils and macrophages), APCs (including macrophages and dendritic cells), and lymphocytes.

* Neutrophils, the most abundant blood leukocyte with a distinctive multilobed segmented nucleus and abundant cytoplasmic lysosomal granules, are rapidly recruited to sites of infection and tissue injury, where they perform phagocytic functions.

* Monocytes are the circulating precursors of tissue macrophages. All tissues contain resident macrophages, which are phagocytic cells that ingest and kill microbes and dead host cells and secrete cyto-kines and chemokines that promote the recruitment of leukocytes from the blood.

* APCs function to display antigens for recognition by lymphocytes and to promote the activation of lymphocytes. APCs include dendritic cells, mononuclear phagocytes, and FDCs.

* B and T lymphocytes express highly diverse and specific antigen receptors and are the cells responsible for the specificity and memory of adaptive immune responses. NK cells are a distinct class of lymphocytes that do not express highly diverse antigen receptors and whose functions are largely in innate immunity. Many surface molecules are differentially expressed on different subsets of lymphocytes as well as on other leukocytes, and these are named according to the CD nomenclature.

* Both B and T lymphocytes arise from a common precursor in the bone marrow. B cell development proceeds in the bone marrow, whereas T cell precursors migrate to and mature in the thymus. After maturing, B and T cells leave the bone marrow and thymus, enter the circulation, and populate peripheral lymphoid organs.

* Naive B and T cells are mature lymphocytes that have not been stimulated by antigen. When they encounter antigen, they differentiate into effector lymphocytes that have functions in protective immune responses. Effector B lymphocytes are antibody-secreting plasma cells. Effector T cells include cytokine-secreting CD4+ helper T cells and CD8+ CTLs.

* Some of the progeny of antigen-activated B and T lymphocytes differentiate into memory cells that survive for long periods in a quiescent state. These memory cells are responsible for the rapid and enhanced responses to subsequent exposures to antigen.

* The organs of the immune system may be divided into the generative organs (bone marrow and thymus), where lymphocytes mature, and the peripheral organs (lymph nodes and spleen), where naive lymphocytes are activated by antigens.

* Bone marrow contains the stem cells for all blood cells, including lymphocytes, and is the site of maturation of all of these cell types except T cells, which mature in the thymus.

* Extracellular fluid (lymph) is constantly drained from tissues through lymphatics into lymph nodes and eventually into the blood. Microbial antigens are carried in soluble form and within dendritic cells in the lymph to lymph nodes, where they are recognized by lymphocytes.

* Lymph nodes are encapsulated secondary lym-phoid organs located throughout the body along lymphatics, where naive B and T cells respond to antigens that are collected by the lymph from peripheral tissues. The spleen is an encapsulated organ in the abdominal cavity where senescent or opsonized blood cells are removed from the circulation, and in which lymphocytes respond to blood-borne antigens. Both lymph nodes and the white pulp of the spleen are organized into B cell zones (the follicles) and T cell zones. The T cell areas are also the sites of residence of mature dendritic cells, which are APCs specialized for the activation of naive T cells. FDCs reside in the B cell areas and serve to activate B cells during humoral immune responses to protein antigens. The development of secondary lymphoid tissues depends on cytokines and lymph node inducer cells.

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