Immunology Lecture 4.pdf

Cancer Biology & Immunology Topic 4 Cells and Tissues of immune system Ass. Prof. Dr. Gharieb El-Sayyad Associate Professor of Medical Microbiology & Immunology, Faculty of Pharmacy, Galala University  Immunization ◼ Immunization...

Cancer Biology & Immunology Topic 4 Cells and Tissues of immune system Ass. Prof. Dr. Gharieb El-Sayyad Associate Professor of Medical Microbiology & Immunology, Faculty of Pharmacy, Galala University  Immunization ◼ Immunization can be conducted actively (natural or artificial) or passively (natural or artificial). Types of immunobiologic agents A. Active Artificial Immunization ◼ Vaccine: is a suspension of live attenuated or killed microorganisms (bacteria or viruses) administered to induce immunity and prevent an infectious disease. Live attenuated viral vaccines (e.g. measles, mumps, rubella, polio) Killed or fractionated viral vaccines (e.g. influenza, hepatitis B, rabies, polio) Killed or fractionated bacterial vaccines (e.g. meningococcal, pneumococcal, cholera) ◼ Toxoid: is a modified bacterial toxin that has been rendered nontoxic but that retains the ability to stimulate the formation of antitoxin (e.g. diphtheria & tetanus toxoids). B. Passive Artificial Immunization ◼ Immuno-globulin (IG) is a sterile solution of human antibodies used for passive immunization against measles and for routine maintenance of immunodeficient individuals. ◼ Specific IG is a special sterile solution of human antibody against a specific disease (e.g. hepatitis B immunoglobulin, HBIG; tetanus immune globulin, TIG). ◼ Antitoxin is a solution of antibodies directed to provide passive immunity as treatment of certain microbial toxins (e.g. botulism antitoxin, diphtheria antitoxin) and poisonous snakebites (e.g. antitoxin against the venom of rattlesnakes).  * Cells and Tissues of Immune System * A. Cells 1. Lymphocytes 2. Mononuclear Phagocytes 3. Dentritic cells 4. Granulocytes B. Lymphoid tissues ◼ Generative organs: Bone marrow, Thymus ◼ Peripheral organs: Lymph nodes, Spleen, Lymphoid tissues ◼ Lymphocytes originate in the bone marrow, mature in different generative organs.  A. Cells I-Lymphocytes All lymphocytes arise from stem cells in the bone marrow. B lymphocytes mature in the bone marrow and T lymphocytes in an organ called the Thymus In the initial stages of their development: they don’t produce surface receptors for antigens and unresponsive to antigens. As they mature: they begin to express antigen receptors, become responsive to antigenic stimulation. 1. Lymphocytes Although all lymphocytes are morphologically similar, they are extremely heterogeneous in function. Lymphocytes are often distinguished by surface proteins, the cluster of differentiation “CD”. CD refers to a molecule recognized by a cluster of monoclonal antibodies that can be used to distinguish lymphocytes. Helper T lymphocytes are CD3+ CD4+ CD8- Cytotoxic T lymphocytes are CD3+ CD4- CD8+ Functions of CD: 1.Cell-cell interactions and adhesion 2.Signals transduction that lead to lymphocyte activation. Summary of Properties of B- and T-lymphocytes  Lymphocyte Classes ◼ B-lymphocytes So called because in birds they were first shown to mature in an organ called the bursa of fabricius. In mammals, B cell maturation occur in the bone marrow. B lymphocytes refer to Bursa or Bone marrow. B-lymphocytes are the only cells capable of producing antibodies. The antigen receptors of B lymphocytes are membrane-bound forms of antibodies. Interaction of antigens with these membrane antibody molecules initiates the sequence of B-cell activation which results in the development of effector cells (plasma cells) that actively secrete antibody molecules.  Lymphocyte Classes T-lymphocytes ◼ They arise from bone marrow and then migrate to and mature in the Thymus (T referring to thymus). ◼ T-lymphocytes are divided (according to the function) into: 1. Helper T cells 2. Cytotoxic or (Cytolytic) T cells 3. Suppressor T cells ◼ T cells don’t produce antibody molecules. 1. Helper T lymphocytes ◼ Helper T-cells recognize and respond to cell surface-antigens but not soluble antigens. ◼ Helper T cells are called so because they help B lymphocytes to produce antibodies and help phagocytes to destroy ingested microbes. ◼ Helper T cells secrete protein hormones called cytokines, whose function is to promote the proliferation and differentiation of the T cells, B cells and macrophages. ▪ Helper T cells fall into 2 functional classes: TH1 cells (inflammatory T cells): activate macrophages to kill the engulfed microbes. TH2 cells (helper T cells): activate B cells to make antibody. 2. Cytolytic T lymphocytes (CTLs) lyse cells that produce foreign antigens such as cells infected by viruses and other intracellular microbes. 3. Suppressor T cells may inhibit immune responses.  II. Mononuclear phagocytes ◼ All mononuclear phagocytes originate in bone marrow, after maturation and activation, they can show different morphologic forms. ◼ Monocytes have bean-shaped nuclei and granular cytoplasm containing lysosomes, phagocytic vacules and cytoskeletal filaments. ◼ Once they settle in tissues, these cells become tissue Macrophages (Histocytes). ◼ Macrophages have functions in: Natural immunity Specific immunity.  III. Dendritic cells They are accessory cells that play important roles in the induction of immune responses. They are with membranous or spine-like projections, and of two types: ◼ Interdigitating dendritic cells ◼ Follicular dendritic cells  IV-Granulocytes ◼ Contain abundant cytoplasmic granules ◼ Participate in the specific immune responses. ◼ Referred as inflammatory cells because they play important roles in inflammation and natural immunity and function to eliminate microbes and dead tissues. ◼ Like macrophages, granulocytes are stimulated by T cell - cytokines. ◼ There are 3 types of granulocytes (according to the staining characteristics of their predominant granules) 1) Neutrophils (Polymorphnuclear leukocytes = PMNs) 2) Eosinophils 3) Basophils (i) Neutrophils (Polymorphnuclear leukocytes = PMNs) Have multilobed, morphologically diverse nuclei. They phagocytose and destroy foreign antigens. They are activated by cytokines produced by macrophages and endothelial cells. They have receptors for IgG antibody. They migrate to and accumulate at sites of complement activation. Therefore, they phagocytose opsonized particles. (ii) Eosinophils ◼ Express receptors for a class of antibody called IgE. ◼ Bind to IgE-coated antigens, such as helminthic parasites (helminthic parasites stimulate the production of IgE). ◼ Helminthes can be killed by specialized granule proteins of eosinophils. ◼ Abundant at sites of immediate hypersensitivity (allergic) reactions. In this setting, eosinophils contribute to inflammation. ◼ Eosinophils growth and differentiation are stimulated by a helper T cell-derived cytokine called interleukin-5 (IL-5). (iii) Basophils ◼ These are the circulatory counterparts of Tissue Mast cells. ◼ Both basophils and mast cells express receptors of high affinity for IgE, therefore bind free IgE Abs. ◼ Subsequent interaction of Ags with these bound IgE molecules stimulates basophils and mast cells to secrete their granule contents, which are the chemical mediators of immediate hypersensitivity.  * Cells and Tissues of Immune System * A. Cells 1. Lymphocytes 2. Mononuclear Phagocytes 3. Dentritic cells 4. Granulocytes B. Lymphoid tissues ◼ Generative organs: Bone marrow, Thymus ◼ Peripheral organs: Lymph nodes, Spleen, Lymphoid tissues ◼ Lymphocytes originate in the bone marrow, mature in different generative organs.  Generative organs (Bone marrow, Thymus) 1. Bone marrow ✓ All blood cells originate from a common stem cell that differentiate into erythroid, megakaryocytic, granulocytic, monocytic and lymphocytic. ✓ The proliferation and maturation of precursor cells in the bone marrow are stimulated by cytokines. ✓ These cytokines are also called “colony-stimulating factors” (CSFs) because they are assessed by their ability to stimulate the growth and development of various leukocyte colonies from marrow cells. 2. Thymus It is bilobed organ situated in the anterior mediastinum, each lobe is divided into multiple lobules by fibrous septa. The thymus has a rich vascular supply and efferent lymphatic vessels that drain into mediastinal lymph nodes. The lymphocytes in the thymus, are T-lymphocytes at various stages of maturation. Precursors of T cell lineage enter the thymus via blood vessels. Bone marrow Thymus  Peripheral organs 1. Lymph nodes They are small nodular aggregates of lymphoid tissue situated along lymphatic channels throughout the body. Epithelia such as the skin and the mucosa of the GIT and respiratory tract as well as connective tissues and most organs have lymphatic drainage. Ags that enter through any of these portals end up in lymphatic vessels and are transported to lymph nodes. 2. Spleen It is an organ weighing approximately 150 gm in adults, located in the left upper quadrant of the abdomen. It is the major site of immune responses to blood-borne Ags, whereas lymph nodes are involved in responses to Ags in the lymph. The spleen is an important filter for clearing blood of unwanted foreign substances and senescent erythrocytes even in the absence of specific immunity.  Peripheral organs 3. Peripheral lymphoid tissues In addition to lymph nodes and spleen, lymphocytes are found either scattered or in aggregates in many tissues. Located beneath the mucosa of the GIT and respiratory tracts are aggregates of lymphocytes and accessory cells that resemble lymph nodes in structure and function. Dr. Gharieb S. El-Sayyad