Cells of Immune System PDF - Immunology Past Paper

Paper : 10 Immunology Module : 05 Phylogeny and Ontogeny of immune system: Cells of immune system Development Team Principal Investigator : Prof. Neeta Sehgal Department of...

Paper : 10 Immunology Module : 05 Phylogeny and Ontogeny of immune system: Cells of immune system Development Team Principal Investigator : Prof. Neeta Sehgal Department of Zoology, University of Delhi Co-Principal Investigator : Prof. D.K. Singh Department of Zoology, University of Delhi Paper Coordinator : Prof. Anju Shrivastava Department of Zoology, University of Delhi Content Writer : Dr. Ravi Toteja Acharya Narendra Dev College, University of Delhi Content Reviewer : Prof. Sukhmahendra Singh Banaras Hindu University 1 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  Description of Module Subject Name ZOOLOGY Paper Name Zool 010: Immunology Module Name/Title Phylogeny and Ontogeny of immune system: Module ID M05: Cells of immune system Keywords Hematopoiesis, B-cells, T-cells, Natural Killer cells, Monocytes, Macrophages, Dendritic cells, Neutrophils, Basophils, eosinophils, Mast Cells Contents 1. Learning objectives 2. Introduction 3. Hematopoiesis 4. Cells of the immune system a. B-cells b. T-cells c. Natural Killer cells d. Monocytes e. Macrophages f. Dendritic cells g. Neutrophils h. Basophils and eosinophils i. Mast Cells 5. Summary 2 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  1. Learning objectives  Process of generation of immune cells  Various types of cells involved in innate and adaptive immunity  Functions of various cell types in generation of immune response. 2. Introduction The response to pathogens is coordinated by the complicated interactions and activities of the large number of different cell types involved in the immune response. The innate immune response is the first line of defense and occurs soon after the exposure of pathogen. Innate immune response is carried out by phagocytic cells (neutrophils and macrophages), natural killer (NK) cells, and granulocytes. The adaptive immune response includes antigen-specific defense mechanisms and may take days to develop. Cell types with critical roles in adaptive immunity are antigen-presenting cells including macrophages and dendritic cells. Antigen- dependent stimulation of various cell types including T cell, B cells, and macrophages all play critical roles in host defense. The immune system has large collection of cells, not only lymphocytes but also phagocytes and their relatives. Some immune cells take on all comers, while others are trained on highly specific targets. The immune system stores just a few of each kind of the different cells needed to recognize millions of possible enemies. When an antigen appears, those few matching cells multiply into a full-scale army. After their job is done, they fade away, leaving sentries behind to watch for future attacks. 3. Hematopoiesis The term hematopoiesis refers to the formation and development of the cells of the blood. Hematopoiesis is a continuous process throughout adulthood. It is estimated that the average human produces 3.7X1011 blood cells per day. This process is regulated by complex mechanisms (Fig. 1). Cell division and differentiation during hematopoiesis are balanced by apoptosis (Programmed Cell Death). If apoptosis fails, a leukemic state can occur. 3 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  In humans, this process begins in the yolk sac in the first weeks of embryonic development. By the third month of gestation, stem cells migrate to the fetal liver and then to the spleen (between 3-7 months gestation these two organs play a major hempatopoietic role). Next, the bone marrow becomes the major hematopoietic organ and hematopoiesis ceases in the liver and spleen. Every functional specialized mature blood cell is derived from a common stem cell. These stem cells are therefore, pluripotent. These stem cells represent a self-renewing population of cells. These cells have the potential to differentiate and to become committed to a particular blood cell lineage. Pluripotent stem cells differentiate into two major pathways - lymphoid and myeloid. Stem cells then become progenitor cells for each type of mature blood cell. These cells have lost the capacity for self-renewal and are committed to a given cell lineage. The myeloid progenitors develop into the cells that respond early and non-specifically to infection. Neutrophils engulf bacteria upon contact and send out warning signals. Monocytes turn into macrophages in body tissues and phagocytose foreign invaders. Granule-containing cells such as eosinophils attack parasites, while basophils release granules containing histamine and other allergy-related molecules. Lymphoid progenitors develop into lymphocytes. Lymphocytes respond later in infection. They mount specific attack involving antigen-presenting cells such as dendritic cells (or macrophages). Progenitor commitment depends upon the acquisition responsiveness to certain growth factors. The particular microenvironment, hematopoiesis inducing microenvironment (HIM) within which the progenitor cell resides controls differentiation. The hematopoietic cells grow and mature on a meshwork of stromal cells, which are non-hematopoietic cells that support the growth and differentiation of the hematopoietic cells. The meshwork of stromal cells includes--fat cells, endothelial cells, fibroblasts, and macrophages. Some of the hematopoietic growth factors are  Colony Stimulating Factors (CSFs).  Multilineage Colony Stimulating Factor (multi-CSF or IL-3). 4 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system   Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF).  Macrophage Colony Stimulating Factor (M-CSF).  Granulocyte Colony Stimulating Factor (G-CSF).  Erythropoietin - Induces terminal erythrocyte development and regulates RBC production.  Interleukins - IL-4, IL-5, IL-6, IL-7, Il-8, IL-9 CSFs- act in a stepwise manner inducing proper maturation. IL-3 [multi-CSF] acts early, possibly even at the level of the pluripotent stem cell, to induce formation of the nonlymphoid cells (erythrocytes, monocytes, granulocytes [neutrophils, eosinophils, basophils], and megakaryocytes). GM-CSF acts at a slightly later stage, but it also induces formation of all the nonlymphoid blood cells. M-CSF and G-CSF act still later to promote the formation of monocytes and granulocytic cells, respectively. IL-4 - stimulates B progenitors, mast progenitors, and basophil progenitors IL-5 - stimulates eosinophil progenitor IL-6 - stimulates the myeloid stem cell IL-7 - induces the differentiation of lymphoid progenitor into B progenitor and T progenitor IL-8 - stimulates the neutrophil progenitor IL-9 - stimulates mast cell growth 5 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  Fig. 1: Diagram showing the process of haematopoiesis Source: https://en.wikipedia.org/wiki/Haematopoiesis Fig. 2: Origin and differentiation of cells of the immune system. 6 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  4. Cells of the immune system a. B-cells: B cells account for 10–15% of circulating lymphocytes. They are called B cells because they were first discovered to mature in the ‘Bursa of Fabricius’ in birds. Humans do not have this organ, and B cell maturation takes place in bone marrow. Therefore, the name of the cells remains as B cells. B cells circulate around the body in the blood stream. When activated, they release huge amount of antibodies. The major function of B lymphocytes is to develop into antibody-secreting plasma cells after stimulation by antigens (bacteria, viruses, tumor cells etc.). Antibodies are specialized protein molecules that specifically recognize and bind to specific antigens that caused their stimulation. Antibody production and binding to foreign antigens is often critical as a means of signaling other cells to engulf, kill or remove that substance from the body. Lymphocytes destined to become B cells move to bone marrowinstead of Thymus to mature (Fig. 2). After addition of cell receptors (antibodies) these are released into the blood. Once released, they move to the lymphoid tissue of the body. B cells play two important roles in providing the protection to the body: 1. Antibody production against the appropriate target antigen 2. Presenting antigens to T cells and therefore providing signals for T cell activation. The majority of B cell activation takes place in the lymph nodes. Certain types of cells in the lymph nodes eat anything foreign and present them to B and T cells. Any B cell that shares a receptor for this substance will be activated and start to multiply. B cells can also be activated by helper T cells. After activation, active B cells migrate around the body and change into plasma cells. Plasma cells: Plasma cells are B cells that are responsible for the production and secretion of a single antibody type. This secretion gives rise to the antibodies found in the circulation. Immunity is kept for as long as the plasma cell continues to secrete antibodies. 7 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  Memory B cells: Memory B cells are also formed after stimulation. These cells migrate to the lymph nodes, where they remain ready for further rounds of activation should the same antigen ever be encountered again. b. T-cells: T lymphocytes are usually divided into two major subsets that are functionally and phenotypically different. T helper (TH) cells, also called CD4+ T cells, are involved in coordination and regulation of immunological responses. They function to mediate responses by the secretion of cytokines that stimulate B lymphocytes to secrete antibodies and Tc cells to get activated in cytotoxic T lymphocytes (CTLs). The second type of T lymphocytes is cytotoxic T lymphocytes or CD8+ T cells. These cells are involved in directly killing of tumor cells, virus-infected cells or self-altered cell. CD8+ T cells are also important in down-regulation of immune responses. Both types of T cells can be found throughout the body, most conspicuously in lymphoid organs (lymph nodes and spleen) but also the liver, lung, blood, and the intestinal tract. Fig. 3: Three types of lymphocytes involved in the immune response against infectious agents in the human body. Source:http://www.open.edu/openlearnworks/mod/oucontent/view.php?id=105&section=1.4.3 8 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  c. Natural Killer cells: Natural killer cells are similar to Tc (CD8+ T cells). They function as effector cells that directly kill certain tumors and virus-infected cells. However, NK cells, unlike the CD8+ (Tc) cells, kill their target cells without need for recognition of antigen in association with MHC molecules. d. Monocytes: Monocytes are a type of white blood cell. They are the largest type of WBCs and can differentiate into macrophages. Monocytes compose 2% to 10% of all leukocytes in the human body. As the monocytes begin to travel, they enter major organs such as the liver and the pancreas. As a part of the vertebrate innate immune system monocytes also influence the process of adaptive immunity. e. Macrophages: Besides their role in phagocytosis, they may function as antigen-presenting cells (APCs) because they ingest foreign materials and present these antigens to other cells of the immune system such as T-cells and B-cells. This is the first step in the initiation of an immunological response (Fig. 4). Macrophages, stimulated by certain cytokines, exhibit increased levels of phagocytosis and are also secrete cytokines that modulate immune responses. Fig. 4: Steps of a macrophage ingesting a pathogen. (Source: https://en.wikipedia.org/wiki/Macrophage) 9 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  a. Ingestion through phagocytosis, a phagosome is formed b. The fusion of lysosomes with the phagosome creates a phagolysosome; the pathogen is broken down by enzymes c. Waste material is expelled or assimilated (the latter not pictured) Parts: 1. Pathogens 2. Phagosome 3. Lysosomes 4. Waste material 5. Cytoplasm 6. Cell membrane Fig. 4 b: Various types of macrophages Source: http://www.nature.com/nri/journal/v15/n12/abs/nri3920.html 10 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  f. Dendritic cells: Dendritic cells also originate in the bone marrow and function as antigen presenting cells (APCs). Dendritic cells are more efficient APCs than macrophages. These cells are found in lymphoid organs (thymus, lymph nodes and spleen), bloodstream and other tissues of the body (Fig. 5). They capture and process antigens in lymphoid organs where an immunological response is initiated. Fig. 5: Dendritic cells in skin Source: https://en.wikipedia.org/wiki/Dendritic_cell g. Neutrophils: Neutrophils are phagocytes that travel throughout the body. These cells are normally found in the bloodstream and are the most abundant type of phagocyte (Fig. 6). During the acute phase of inflammation neutrophils migrate toward the site of inflammation and are usually the first cells to arrive at the scene of infection(Fig. 7). 11 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  Fig. 6: Neutrophils with segmented nuclei surrounded by erythrocytes. Intra-cellular granules are visible in the cytoplasm (Giemsa stained). Source: https://en.wikipedia.org/wiki/Neutrophil Fig. 7: A Phagocyte in Action: Neutrophil engulfing anthrax bacteria.. Scale bar is 5 micrometers. Source: https://www.boundless.com/microbiology/textbooks/boundless-microbiology-textbook/ immunology- 11/overview-of-immunity-135/cells-and-organs-of-the-immune-system-694-3503/ h. Basophils and eosinophils: Basophils and eosinophils are related to neutrophils (Fig. 8). They secrete chemical mediators that are involved in defending against parasites, and play a role in allergic reactions, such as asthma. 12 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  Fig. 8: Basophil and Eosinophil Source: https://simple.wikipedia.org/wiki/Basophil, https://en.wikipedia.org/wiki/Eosinophil i. Mast Cells: Mast cells reside in connective tissues and mucous membranes, and regulate the inflammatory response (Fig. 9). They are most often associated with allergy and anaphylaxis Fig. 9: Mast cell Source: https://en.wikipedia.org/wiki/Mast_cell 5. Summary Both adaptive and innate responses are carried out by number of cell types. These cells are formed in bone marrow by the process of hematopoiesis. Following is the brief summary of various cell types involved in generation of immune response. 13 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  B cell (B lymphocyte): A white blood cell that produces antibodies specific to the antigen. Basophil: A white blood cell that releases histamine (a substance involved in allergic reactions) and that produces substances to attract other white blood cells (neutrophils and eosinophils) to a site of injury. Dendritic cell: A cell that is derived from white blood cells, resides in tissues, and helps T cells recognize foreign antigens. Eosinophil: A white blood cell that kills bacteria, that kills other foreign cells too big to ingest, that may help immobilize and kill parasites, that participates in allergic reactions, and that may help destroy cancer cells. Helper T cell (TH Cell): A white blood cell that helps B cells produce antibodies against foreign antigens, that helps killer T cells become active, and that stimulates macrophages. Killer T cell (TC Cell): A T cell that attaches to infected cells and cancer cells and kills them. Leukocyte: A white blood cell, such as a monocyte, a neutrophil, an eosinophil, a basophil, or a lymphocyte (a B cell or T cell). Lymphocyte: The white blood cell responsible for acquired (specific) immunity, including producing antibodies (by B cells), distinguishing self from nonself (by T cells), and killing infected cells and cancer cells (by killer T cells). Macrophage: A large cell that develops from a white blood cell called a monocyte, that ingests bacteria and other foreign cells, that helps T cells identify microorganisms and other foreign substances, and that is normally present in the lungs, skin, liver, and other tissues. Mast cell: A cell in tissues that releases histamine and other substances involved in inflammatory and allergic reactions. Natural killer cell: A type of white blood cell that can recognize and kill abnormal cells, such as certain infected cells and cancer cells, without having to first learn that the cells are abnormal. Neutrophil: A white blood cell that ingests and kills bacteria and other foreign cells. 14 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system  Phagocyte: A type of cell (such as a neutrophil or macrophage) that ingests and kills or destroys invading microorganisms, other cells, and cell fragments. Regulatory (suppressor) T cell: A white blood cell that helps end an immune response. T cell (T lymphocyte): A white blood cell that is involved in acquired immunity and that may be one of three types: helper, killer (cytotoxic), or regulatory. 15 ZOOLOGY Immunology Phylogeny and Ontogeny of immune system: Cells of immune system