Lecture 3. Immunology Lecture Notes PDF

BIO 471 – Immunology Cells and tissues of the immune system Andria Michael, B.Sc., M.Sc., Ph.D. What we will discuss today Cells of the Immune System Phagocytes Mast cells Basophils & Eosinophils Dendritic Cells Lymphocytes Natural Killer cells Anatomy and...

BIO 471 – Immunology Cells and tissues of the immune system Andria Michael, B.Sc., M.Sc., Ph.D. What we will discuss today Cells of the Immune System Phagocytes Mast cells Basophils & Eosinophils Dendritic Cells Lymphocytes Natural Killer cells Anatomy and Functions of Lymphoid Tissues Bone Marrow & Thymus Lymphatic System Lymph Nodes Spleen Cutaneous & Mucosal Immune Systems The origins of the immune cells Phagocytes Phagocytes Include neutrophils and macrophages Primary function: Ingest and destroy microbes Remove damaged tissue Functional response: 1. recruitment of the cells to the sites of infection 2. recognition of and activation by microbes 3. ingestion of the microbes (phagocytosis) 4. destruction of ingested microbes Secrete cytokines to communicate with other cells to promote/regulate immune responses Neutrophils vs Macrophages Neutrophils Most abundant WBC population Key factor in acute inflammation 12-15µm in diameter with numerous membranous projections Nucleus segmented in 3-5 connected lobules hence called polymorphonuclear leukocytes (PMNs) In the cytoplasm: 2 types of membrane-bound granules Specific granules filled with enzymes (such as lysozyme, collagenase & elastase) Azurophilic granules filled with enzymes (i.e. myeloperoxidase) & microbicidal substances (i.e. defensins & cathelcidins) Production of neutrophils is stimulated by granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF)  Neutrophils 1 x 1011 per day Circulate the blood for a few hours or up to 5 days before dying Major function of neutrophils Development of Macrophages and Monocytes Development of Macrophages and Monocytes After birth, cells of the monocyte-macrophage lineage arise from committed precursor cells in the bone marrow, driven by a cytokine called monocyte (or macrophage) colony-stimulating factor (MCSF) These precursors mature into monocytes, which enter and circulate in the blood Blood monocytes are efficiently recruited into tissue sites of infection or injury, and therefore most macrophages at sites of inflammation are monocyte-derived. Most long-lived tissue-resident macrophages are derived not from the bone marrow but from yolk sac or fetal liver precursors during fetal development. They often assume specialized phenotypes depending on the organ Subsets of Monocytes 10-15µm in diameter & bean-shaped nuclei Finely granular cytoplasm containing lysosomes, phagocytic vacuoles, and cytoskeletal filaments Express class II major histocompatibility complex (MHC) molecules Heterogeneous Distinguished by cell surface markers and functions (not by morphology) Classical or inflammatory monocytes, (90% to 95% of blood monocytes) produce inflammatory mediators, are phagocytic, and are rapidly recruited to sites of infection or tissue injury Circulating monocyte, called nonclassical monocytes (5-10% of blood monocytes), are recruited into tissues after infection or injury and may contribute to repair.  Functions of Macrophages secrete Tissue-resident macrophages Cytokines Initiate and amplify the protective response against microbes Enhance recruitment of monocytes and other leukocytes from the blood to infection site Stimulate leukocyte migration to the infected/damaged tissue  Functions of Macrophages undergo Engulfed microbes Leads to release of cytokines → enhance immune response  Functions of Macrophages Macrophages ingest Macrophages can necrotic host cells, specifically recognize including cells that die in and engulf cells that die tissues because of the by apoptosis (including effects of toxins, trauma, apoptotic neutrophils) and neutrophils that die before the dead cells after accumulating at can release their sites of infection. This is contents and induce part of the cleaning-up inflammatory responses. process. Ingest necrotic host cells  Functions of Macrophages Macrophages also function as antigen-presenting cells (APCs) Display fragments of protein antigens to T cells & activate their recruitment to the injury site or infection  Functions of Macrophages Macrophages promote tissue repair Stimulate angiogenesis Fibrosis  Macrophage receptors and activation Macrophages get activated by recognizing various different microbial molecules, as well as host molecules produced in response to infections and injuries These molecules bind to specific signalling receptors located on the surface of macrophages Subsets of Macrophages Mast Cells Mast cells Bone marrow-derived cells Most abundant in the skin and mucosal epithelia Upon activation → release many potent inflammatory mediators that defend against infections by helminthic parasites or cause symptoms of allergic diseases Mature mast cells are found in tissues & usually adjacent to small blood vessels and nerves Cytoplasm contains numerous membrane-bound granules, which are filled with preformed inflammatory mediators, such as histamine, and acidic proteoglycans Various stimuli can activate mast cells to release the cytoplasmic granule contents into the extracellular space, as well as to synthesize and release cytokines and inflammatory lipid mediators The released histamine and other mediators promote changes in the blood vessels that cause inflammation Mast cells express IgE receptors. When these bind to an antigen → mast cell activation Basophils Basophils Granulocytes Derived from haematopoietic precursors Mature in bone marrow Circulate in the blood germinal centre)  Anatomic organization of B & T lymphocytes T lymphocytes are located mainly beneath and more central to the follicles, in the paracortical cords Naive T cells enter the T cell zones through specialized cortical blood vessels called high endothelial venules (HEVs) The anatomic segregation of B and T lymphocytes in distinct areas of the node is dependent on chemokines (chemoattractant cytokines), that direct the migration of the lymphocytes These specialized cells are fibroblastic reticular cells (FRCs) in the T cell zones and follicular dendritic cells (FDCs) in the follicles  Anatomic organization of B & T lymphocytes Some types of FRC that play central roles in maintaining the structure and functions of lymph nodes include: Marginal reticular cells that form the subcapsular sinus floor Perivascular reticular cells that form layers around HEVs T cell zone FRCs that direct movement of T cells and DCs within the lymph node B cell zone FRCs that direct movement of B and T cells in and out of B cell follicles  Anatomic organization of B & T lymphocytes After stimulation by protein antigens, B and T cells change their expression of chemokine receptors and begin to migrate toward one another in response to signals from chemokines and other mediators Activated T cells either migrate toward follicles to help B cells or exit the node and enter the circulation Activated B cells migrate into germinal centres and, after differentiation into plasma cells, may home to the bone marrow  Antigen Transport Through Lymph Nodes Lymph-borne substances that enter the subcapsular sinus of the lymph node are sorted by molecular size and delivered to DCs, macrophages, and FDCs to initiate T and B cell responses Microbes and high-molecular-weight antigens are taken up by sinus macrophages and presented to cortical B lymphocytes just beneath the sinus Low-molecular-weight soluble antigens are transported out of the sinus through the FRC conduits and passed to resident cortical DCs located adjacent to the conduits  The Spleen Highly vascularized organ Secondary lymphoid organ with other non-immunological Major functions: to remove aging and damaged blood cells and particles from the circulation to initiate adaptive immune responses to blood-borne antigens Capsule with fibrous partitions (SEPTAE) Lymphocytes enter & leave mainly via blood stream (good blood supply, most antigens travel by blood)  The Spleen Immunological role: as for lymph nodes wth germinal centres developing during immune responses The splenic parenchyma is divded into: Red pulp (composed mainly of blood- filled vascular sinusoids) White pulp (lymphocyte-rich) Red pulp Filters damaged or aged red blood cells White pulp Periarteriolal Lymphoid Sheath (PALS) - % associated clusters of lymphocytes – the lymphatic follicles or nodules Follicles similar to those in lymph nodes  The Spleen Blood enters the spleen through a single splenic artery that pierces the capsule at the hilum and divides into progressively smaller branches that remain surrounded by protective and supporting fibrous trabeculae Some of the arteriolar branches of the splenic artery end in extensive vascular sinusoids, filled with large numbers of erythrocytes, and lined by macrophages and other cells The sinusoids end in venules that drain into the splenic vein, which carries blood out of the spleen and into the portal circulation The macrophages serve as a blood filter, removing microbes, damaged cells, and antibody- coated cells and microbes  The Spleen The white pulp contains the cells that mediate adaptive immune responses to blood-borne antigens In the white pulp are many collections of densely packed lymphocytes, which appear as white nodules against the background of the vascular sinusoids The white pulp is organized around central arteries, which are branches of the splenic artery distinct from the branches that form the vascular sinusoids Several smaller branches of each central artery pass through the lymphocyte-rich area and drain into a marginal sinus  The Spleen A region of specialized cells surrounding the marginal sinus, called the marginal zone, forms the boundary between the red pulp and white pulp The central arteries are surrounded by cuffs of lymphocytes, most of which are T cells; T cell zones periarteriolar lymphoid sheaths (PALS). B cell–rich follicles occupy the space between the marginal sinus and the periarteriolar sheath The marginal zone just outside the marginal sinus is a distinct region populated by B cells and specialized macrophages The B cells in the marginal zone, known as marginal zone B cells, are functionally distinct from follicular B cells Antigens in the blood are delivered into the marginal sinus by circulating DCs or are sampled by the macrophages in the marginal zone The anatomic arrangements of the APCs, B cells, and T cells in the splenic white pulp promote the interactions required for the efficient development of humoral immune responses The segregation of T lymphocytes in the periarteriolar lymphoid sheaths and B cells in follicles and marginal zones is dependent on the production of different cytokines and chemokines by the stromal cells in these different areas, analogous to the case for lymph nodes  Mucosa-associated lymphoid tissue (MALT) Diffusely distributed lymphoid tissues in lining (mucosae) of gastrointestinal, respiratory & urinogenital tracts Gut-associated lymphoid tissue (GALT) & bronchus ALT (BALT) are the best characterised ones GALT made up of Peyer’s patches & isolated follicles in colonic submucosa Lymphocytes also found in: lamina propria intestinal epithelium lumen of intestine Peyer’s patches Aggregates of lymphocytes; B cells from central follicle surrounded by T cells and macrophages Have efferent lymphatics that drain into mesenteric lymph nodes, but not afferent lymphatics Covered by specialised lymphoepithelium consisting of cells known as M cells Antigen in the gut enters via M cells that selectively take up particles & deliver them to lymphoid follicles also by specialised dendritic cells which ‘reach’ into the gut lumen Gap & holes, clumps of lymphocytes, lymphy areas Summary The anatomic organization of the cells and tissues of the immune system The different cells of the immune system and their function Lymphocyte development and maturation Lymphoid organs