Microbiology

Immune system – Cells and organs Dr P Ramjathan Department of Microbiology Cells and Organs of Immune system Part 1 • White blood cells Part 2 • Lymph nodes • Spleen • Bone marrow • Thymus Part 1 : cells of the immune system Origin of Leucocytes Pleuripotent stem cell Leukocytes • White blood cells that provide either innate or specific adaptive immunity. • Myeloid Cells: First line of defense, non-specific innate immunity (eg. when exposed to a microbe for the first time) • Neutrophils • Eosinophils • Basophils/Mast cells • Monocytes/Macrophages/Dendritic Cells BEN M baso, eosi, neutro, mono(mac and den) • Lymphoid Cells: Humoral and Cell Mediated specific immunity • B Lymphocytes • • T Lymphocytes (Helper and Cytolytic) • Lymphoid Cells: non-specific immunity • Natural Killer Cells Myeloid cells Neutrophils Neutrophils are produced in the bone marrow from • myeloblast-type stem cells • often called polymorphonuclear cells (PMN's). • Multilobed nucleus • The neutrophil's main role is in inflammation. – First to arrive at inflammation site – Leave blood/endothelium into tissue (extravasation). • Neutrophils are attracted into the tissue by chemotactic factors stimulated by tissue damage Neutrophils • In the tissues, neutrophils are active phagocytes. • They destroy ingested microorganisms via oxygen dependent or independent pathways. • Produce myeloperoxidases to assist with destroying microbes. Eosinophil • Granulocytes stain intensely with 'eosin’; bilobed nucleus. • Contain basic crystal granules in cytoplasm to mediate toxic reactions to large parasites. • Eosinophils are motile, sometimes phagocytic, and are particularly active in parasitic infection. Basophils • Found in low numbers in the blood. Act like mast cells. • Involved in Type I hypersensitivity responses. • Have high affinity receptors for IgE on their surface. • Cross-linking of the IgE causes the basophils to release inflammatory mediators (histamine, prostaglandins, leukotrienes). Mast Cells • Formed in tissue from undifferentiated bone marrow precursors. • Similar importance in allergic reactions as basophils, but only found in tissues. • Contain granules with preformed mediators to be released • after stimulation – histamine, prostaglandins – leukotrienes • Stimulation of mast cells occurs • by the anaphylatoxins • complement or • by cross-linking of surface immunoglobulin (IgE). Cells of the Reticuloendothelial System • The “phagocytic system” of the body, including fixed macrophages of tissues • Cells of the RES provide natural immunity against microorganisms • phagocytosis and intracellular killing of microbes • Immune cell Recruitment via molecular mediators • Presentation of peptide antigens to lymphocytes • Cells of the RES include: • circulating monocytes • resident macrophages in the liver, spleen, lymph nodes, thymus, submucosal tissues of the respiratory and alimentary tracts • macrophage-like cells including dendritic cells in lymph nodes, Langerhans cells in skin, and glial cells in the central nervous system. Monocytes/Macrophages • Monocytes circulate in the blood after leaving the bone marrow. • Survive only a day or so before they enter the tissue to mature into macrophages. • Involved in phagocytosis and intracellular killing of microorganisms. • Chew ingested proteins via degradative enzymes. • Generation of toxic metabolites through respiratory burst eg. nitric oxide, hydrogen peroxide, superoxide anion. • Monocytes/Macrophages are also antigen processing and presenting cells. • Present to adaptive cells (lymphocytes) Macrophages • When monocytes enter the tissues and become macrophages: – Enlarge and increase production of intracellular lysozymes – Greater phagocytosis. – Can live for years in tissue; highly motile. • Activation of these cells occurs by phagocytosis of antigens, or in response to T cell derived cytokines. Activated macrophages recognize and remove unwanted invading organisms. Dendritic Cells • Specialized phagocytic cells. • Found in most tissues. • Abundant at interfaces between the external and internal environments (skin, lining of the gastrointestinal tract), where they encounter invading pathogens. • Innate immune system responds to microbes quickly as it does not need prior exposure and is non specific. Adaptive immunity responds more slowly as this is a more specific immune response directed against a specific antigen. Natural Killer Cells • Part of innate immunity. • Cells that kill viral infected or tumor target cells. • Killing is nonspecific - they do not need to recognize foreign antigens presented on the target cell. • NK cells do not have a specific cell receptor. • Target recognition occurs by a Killer Inhibitory Receptor, KIR, which is lacking on infected and tumor targets. • Kills targets by releasing perforin which damages target cell membranes. B Lymphocytes • Develop from stem cells in the bone marrow. • Produce antibodies with specificity for antigens. • Plasma cells = Activated B cells • Plasma cells produce antibody Activation of B Lymphocytes • Activation into antibody secreting cells is antigen-dependent. • Antigen binding to surface Ig molecules triggers differentiation into plasma cells. B cells and antibody production T Cells • A T cell is a type of lymphocyte, a white blood cell. • The "T" in T cell stands for thymus. • The thymus is where T cells mature. • Types • Cytotoxic T cells (Tc cells) • Helper T cells, (Th cells) • Regulatory T cells (Treg cells), used to be called suppressor T cells • Natural Killer T cells (NKT cells) T Lymphocytes • T lymphocytes regulate immune responses. • Integral in cell mediated immunity. • Mature T cells display either CD4 or CD8. • Develop in the thymus. • Cells with a CD4 marker are called helper T cells (Th cells). • CD8 marker positive cells are cytotoxic T cells (Tc cells). • Each T cell has a T cell receptor (TCR )to recognize antigen Terminology: Cluster Of Differentiation (CD) • Unique cell surface molecules. • Molecules given number designations. • The acronym CD describes the cluster of unique determinant • The number describes the order in which it was discovered. T Helper Cells • All express the CD4 molecule. • Aid effector T lymphocytes in cell-mediated immunity and • aid antigen-stimulated subsets of B cells to proliferate and differentiate toward antibody-producing cells. T cytotoxic cells • T cytotoxic cells (CTLs) are cytotoxic against tumor cells and host cells infected with intracellular pathogens. • These cells express CD8. T Suppressor/Regulatory Cells • Suppress T and B cell responses. • Serve as regulators of T cell responses. Antigen Presenting Cells (APCs) • APCs are found primarily in the skin, lymph nodes, spleen and thymus. • These cells process antigens and present them to T-cells. • Professional antigen-presenting cells, including macrophages, B cells and dendritic cells. • Present foreign antigens to helper T cells, and/or cytotoxic T cells. • An antigen-presenting cell (APC) is a cell that displays antigen complexed with major histocompatibility complexes (MHCs) on their surfaces. • This process is known as antigen presentation. • T cells may recognize these complexes using their T cell receptors (TCRs). • Antigen-presenting cells are vital for effective adaptive immune response, as the functioning of both cytotoxic and helper T cells is dependent on APCs. • Antigen presentation allows for specificity of adaptive immunity Antigen presentation • After dendritic cells( in various parts of body) have phagocytosed pathogens, they usually migrate to the vast network of lymph vessels and are carried by lymph flow to the draining lymph nodes. • Each lymph node is a collection point where APCs can interact with T cells. • The antigen is digested into smaller peptides containing epitopes, which are then presented to T cells by the MHC.( major histocompatibility complex) • Antigen presentation activates the immune system via cytokines and can lead to antibody production or activation of other cells. • Antibodies formed are specific to a particular antigen. Antigen presentation Part 2 : organs of the immune system ORGANS Primary/Secondary Lymphoid Tissues • Primary: - Adult Bone Marrow - Thymus Gland • Secondary: - Spleen - Lymph Nodes - Tonsils - Appendix - Peyer’s patches - Aggregates of cells in lamina propria (GALT, BALT, MALT) Primary lymphoid organs: Thymus: encapsulated organ where T cells mature and are selected based in part on their ability to not recognize the host Bone Marrow: site of remaining hematopoiesis, B cells mature here, mostly in skull, ribs, sternum and pelvis Thymus • Thymocytes are educated to become T lymphocytes here. •Expression of specific receptors. •T cells learn to recognize self as self so that immune cells don’t kill bodies own cells. Lymph Nodes Lymphoid Tissue: • Specialized connective tissue and organs where lymphocytes form the major cellular component. • Physical location for interaction between leukocytes – Myeloid (innate) – Lymphoid (specific) • Contains high numbers of lymphocytes that mediate responses. • Cellular immunity (protection from pathogens) • Humoral immunity (immunoglobulin production) Lymph nodes • The substance of the lymph node is divided into the outer cortex and the inner medulla. • B cells are mainly found in the outer (superficial cortex) where they are clustered together as follicular B cells in lymphoid follicles and the T cells are mainly in the paracortex. • The number and composition of follicles can change especially when challenged by an antigen, when they develop a germinal center. • Lymph enters the lymph node through multiple afferent lymphatic vessels, and flows through spaces called sinuses. • Sinuses drain the filtered lymphatic fluid into the medullary sinuses, from where the lymph flows into the efferent lymph vessels to exit the node. Spleen Spleen •Defense against microorganisms in blood, filters blood. •Site of removal of aged or abnormal RBCs/platelets •Capsule with trabeculae •Comprised of splenic pulp – Red pulp and White pulp with follicles •Supported by network of reticular fibers •Largest lymphoid organ Lecture Objectives: •Identify cell types involved in the innate and adaptive immune response. •Understand structure and function of primary and secondary lymphoid organs.