CELLS & ORGANS OF THE IMMUNE SYSTEM A Presentation By Isaac U.M., Associate Professor & HOD, Dept. of Microbiology. College of Medicine, International Medical & Technological University, Dar-Es-Salaam, Tanzania
Introduction <ul><li>The many cells, organs and tissues of the immune system are found throughout the body. </li></ul><ul><li>They are functionally classified into two main groups. </li></ul><ul><ul><li>Primary lymphoid organs: Provide appropriate microenvironment for the development and maturation of lymphocytes. </li></ul></ul><ul><ul><li>Secondary lymphoid organs: Trap antigen, generally from nearby tissues or vascular spaces and are sites where mature lymphocytes can interact effectively with antigen. </li></ul></ul><ul><li>Blood vessels and lymphatic systems connect these organs, uniting them into a functional whole. </li></ul><ul><li>Carried within the blood and lymph and populating the lymphoid organs are various white blood cells, or leukocytes, that participate in the immune response. </li></ul><ul><li>Of these cells, only the antigen-specific lymphocytes posses the attributes of diversity, specificity, memory and self-nonself recognition, the hallmarks of an adaptive immune response. </li></ul>
Introduction <ul><li>Other leukocytes also play important roles, some as antigen presenting cells and others participating as effector cells in the elimination of antigen by phagocytosis or the secretion of immune effector molecules. </li></ul><ul><li>Some leukocytes, especially T lymphocytes, secrete various protein molecules called cytokines. </li></ul><ul><li>These molecules act as immunoregulatory hormones and play important roles in the coordination and regulation of immune responses. </li></ul>
Hematopoiesis <ul><li>All blood cells arise from a type of cell called the hematopoietic stem cell (HSC). </li></ul><ul><li>Stem cells are cells that can differentiate into other cell types. </li></ul><ul><li>They are self renewing, maintaining their population level by cell division. </li></ul><ul><li>In humans, hematopoiesis, the formation and development of red and white blood cells, begins in the embryonic yolk sac during the first weeks of development. </li></ul><ul><li>Yolk sac stem cells differentiate into primitive erythroid cells that contain embryonic hemoglobin. </li></ul><ul><li>By the third month of gestation, hematopoietic stem cells have migrated from the yolk sac to the fetal liver and subsequently colinize the spleen; theses two organs have major roles in hematopoiesis from the third to the seventh months of gestation. </li></ul><ul><li>After that, the differentiation of HSCs in the bone marrow becomes the major factor in hematopoiesis, and by birth there is little or no hematopoiesis in then liver and spleen. </li></ul>
Hematopoiesis <ul><li>Early in hematopoiesis, a multipotent stem cell differentiates along one of the two pathways, giving rise to either a lymphoid progenitor cell or a myeloid progenitor cell. </li></ul><ul><li>Progenitor cells have lost the capacity for self-renewal and are committed to a particular cell lineage. </li></ul><ul><li>Lymphoid progenitor cells give rise to B, T, and NK (natural killer ) cells. </li></ul><ul><li>Myeloid stem cells generate progenitors of red blood cells (erythrocytes), many of the various white blood cells(neutrophils, basophils, monocytes, mast cells, dendritic cells), and platelet-generating cells called megacaryocytes. </li></ul><ul><li>In bone marrow, hematopoietic cells and their descendants grow, differentiate, and mature on a mesh-like scaffold of stromal cells, which include fat cells </li></ul>
Selected CD Markers of Importance ADCC, antibody-dependent cellular cytotoxicity; APCs, antigen-presenting cells; CTLA, cytotoxic T-lymphocyte associated protein; EBV, Epstein Barr virus; ICAM, intercellular adhesion molecule; Ig, immunoglobulin; IL, interleukin; LCA, leukocyte common antigen; LFA, leukocyte function-associated antigen; LPS, lipopolysaccharide; MHC, major histocompatibility complex; TAC, T-cell activation complex; TCR, T-cell antigen receptor; VLA, very late activation (antigen). Modified from Male D et al: Advanced immunology , ed 3, St Louis, 1996, Mosby. This table shows the recognized CD markers of hemopoietic cells and their distribution. A filled rectangle or + means cell population present; a half-filled triangle is subpopulation; *, activated cells only; **, markers that identity or are critical to the cell type.
Normal Blood Cell Counts From Abbas AK, Lichtman AH, Pober JS: Cellular and molecular immunology, ed 4, Philadelphia, 2000, WB Saunders.
Eosinophil. These cells have the purpose of giving large parasites such as helminths, a hard time. They attach via C3b receptors, the C3b having been produced during the course of alternative pathway complement activation by the helminth. The eosinophils release various substances from their eosinophilic granules. These include major basic protein (MBP), plus cationic proteins, peroxidase, arylsulphatase B, phospholipase D and histaminase. The granule contents are capable of damaging the parasite membrane
Neutrophil polymorph. Neutrophils , or neutrophil polymorphonuclear leucocytes , respond to chemotactic signals and leave capillaries by a complex process, involving margination (flowing nearer to the endothelial lining of blood vessels), rolling and then attaching (margination), following which they emigrate between the endothelial cells (extravasation, or diapedesis). Several mediators are involved. They include substances produced by micro-organisms, and by the cells participating in the inflammatory process. One such is a substance called interleukin-1 (IL-1), which is released by macrophages as a result of infection or tissue injury. Another is histamine, released by circulating basophils, tissue mast cells, and blood platelets. It causes capillary and venular dilatation. C3a and C5a produced during complement activation, are chemotactic for phagocytic cells. Another group of substances produced are the acute phase proteins. As a consequence of tissue damage, the liver produces a substance called C-reactive protein (CRP), which is so called on account of its ability to attach to the C-polysaccharide component of the cell wall of bacteria and fungi. This activates the complement system by the classical pathway, and as a result C3a is formed and coats the organism, facilitating its phagocytosis .
Conventions for Naming Leukocyte Surface Molecules By one convention, cell surface molecules are named according to a particular function affected by an anti-leukocyte mAb. For example, the lymphocyte function-associated antigen 1 , or LFA-1, was so named because antibodies recognizing this structure interfere with lymphocyte cell adhesion events and optimal lymphocyte function. The second convention is effectively no convention at all. Molecules are named arbitrarily according to individual laboratory preferences. For example, no obvious logic follows in the designations B7 and B220, except that the leading "B" reminds us that these antigens are typically expressed on B lymphocytes. By a third convention, leukocyte cell surface molecules are named systematically by assigning them a cluster of differentiation (CD) antigen number that includes any antibody having an identical and unique reactivity pattern with different leukocyte populations.
The use of in vitro studies to identify cytokines and growth factors regulating hematopoiesis <ul><li>Ex. Colony stimulating factors (CSFs) and erythropoietin (EPO) </li></ul>
- Site of maturation <ul><li>Membrane receptors </li></ul><ul><li>Membrane bound immunoglobulin </li></ul><ul><li>Markers of a mature B cell </li></ul><ul><li>Class II MHC </li></ul><ul><li>B220 </li></ul><ul><li>CR1 and CR2 </li></ul><ul><li>Fc RII </li></ul><ul><li>B7-1, B7-2 </li></ul><ul><li>CD40 </li></ul>B Lymphocytes
- T Lymphocytes <ul><li>Site of maturation </li></ul><ul><li>Membrane receptors </li></ul><ul><li>T Cell Receptor (TCR) </li></ul><ul><li>CD4 </li></ul><ul><li>CD8 </li></ul><ul><li>CD28 </li></ul><ul><li>CD45 </li></ul><ul><li>Classes of T cells </li></ul><ul><li>T helper cells (T H ) </li></ul><ul><li>T cytotoxic cells (T C ) </li></ul><ul><li>Function of T H and T C </li></ul><ul><li>Class restriction </li></ul>
<ul><li>Neurotrophil(polymorphonuclear leukocyte, PMN) </li></ul><ul><li>Morphology </li></ul><ul><li>Function </li></ul><ul><li>Origin, development, and life span </li></ul><ul><li>Leukocytosis and infection </li></ul>
<ul><li>Eosinophil </li></ul><ul><li>Morphology </li></ul><ul><li>Function </li></ul><ul><li>More in Chapter 17 </li></ul>
<ul><li>Basophil </li></ul><ul><li>Morphology </li></ul><ul><li>Function </li></ul><ul><li>Importance in allergic responses </li></ul>