Immune System 4BBY1030 2016-2017 Lectures

The Immune System 4BBY1030 Dr. Brian Stramer [email protected] The Immune System Represents a number of surveillance mechanisms: that respond to infection by micro-organisms. which can help repair damaged tissues. that may help retard cancer development How? The system is capable of recogniz...

The Immune System 4BBY1030 Dr. Brian Stramer [email protected] The Immune System Represents a number of surveillance mechanisms: that respond to infection by micro-organisms. which can help repair damaged tissues. that may help retard cancer development How? The system is capable of recognizing self vs non-self Can secrete protective substances into bodily fluids (humoral immunity) Can launch a cellular response (cellular immunity) The Immune System There are several mechanisms which protect the body before the immune system is invoked. Barriers Both physical and chemical in nature. The skin, mucous membranes and cilia are examples of physical barriers. Chemical barriers include mucous and the acidic properties of the stomach. Surface epithelia can secrete specific microbicidal substances e.g. lysozyme and phospholipase in saliva and tears, and cryptidins and defensins in the gut. Blood also contains antimicrobial substances e.g. complement The Two Arms of the Immune System Ilya metchnikoff Paul Ehrlich Innate Immunity Adaptive Immunity Innate Immunity Innate Immunity Non specific. Rapid. Response to infections (non-self). Response to altered self. Can be humoral or cell mediated. Adaptive Immunity Adaptive Immunity Specific. Slower to develop. Response to infections (non-self). Response to altered self. Can be humoral or cell mediated. Has memory. Cells of the Innate Response Macrophage Neutrophil Highly phagocytic Contain lysosomal and microbiocidal proteins which destroy engulfed bacteria, cellular debris or foreign particulate matter. Neutrophils die after having disposed of their target Macrophages can produce new lysosomes and continue to engulf and destroy foreign material. Macrophages Macrophages can reside in a tissue or wander and survive for several weeks or even months. In certain locations they have specific names as well as specific functions: 1. Liver - kupffer cells 2. Bone - osteoclasts 3. Kidney – mesangial cells 4. Brain - microglia They are also found in lung, lymphoid organs and connective tissue. Kupffer Cells Osteoclasts Neutrophil Action Neutrophils survive for only a few days on leaving the circulatory system and have to be constantly replaced which explains their high concentration among circulating white blood cells Neutrophil wound response Other “Killer” Cells Eosinophil Natural Killer Cell Natural killer cells (lymphocyte lineage) attach to virally infected cells, transplanted cells, and some tumor cells by causing pores to form in the target cell membrane which induces apoptotic death. Eosinophils contain granules with cytotoxic proteins that attach to, and kill, parasites. Adaptive Immune Cells Cells are slower to react than innate immune cells. Respond to a near infinite range of different organisms. Recognize foreign, possibly harmful substances termed antigens. Cells act to neutralize or destroy these foreign substances. Adaptive response can be both cellular and humoral in nature. Adaptive Immune Cells lymphocytes Make up about 30% of WBC population. Different functional classes of lymphocyte: B Cell T Cell Circulate in the blood and lymph and become activated in secondary lymphoid organs B vs T cells B Cells T Cells Arise in bone marrow Arise in bone marrow Mature in the bone marrow Mature in the thymus Activated in 2° lymphoid organs Activated in 2° lymphoid organs Secrete antibodies specific to the target antigen Long term immunity maintained by “memory B cells” Activated to induce a cellmediated adaptive immune response. Long term immunity maintained by “memory T cells” T Cells Direct and recruit other cells of the immune system as well as attacking diseased cells directly. Specific T cell receptors (TCR) are responsible for recognition of antigen. There are four functional subsets : 1.Helper T cells - can activate B cells and/or… 2.Cytotoxic T cells - which can specifically kill infected cells. 3.Regulatory T cells - Help modulate responses. 4.Memory T cells. B Cells Activated by antigen and helped along by helper T cells Secrete antibody when activated. Antibodies can then either: 1. neutralize the pathogen 2. facilitate uptake by phagocytes (opsonization). There are two functional subsets : 1. Plasma cells 2. Memory cells Antigens Substance that may or may not be harmful which activates the immune system. It can be a protein, lipid, carbohydrate, or nucleic acid. Can induce a T cell and/or a B cell response. Antibodies Glycoprotein (immunoglobulins) that interacts with a specific antigen. Can neutralize the antigen (if harmful) or they can coat the antigen to induce phagocytosis (opsonization) by macrophages. Staggering array of diversity. ~ 5x1013 or 5,000,000,000,000 varieties!! Antibodies Antibodies T Cell Receptor Diversity generated by a similar somatic recombination mechanism to antibodies. ~1018 or 1,000,000,000,000,000,000 varieties!! Lymphocyte Activation Antigen presentation via an antigen presenting cell B T B B Th Clonal Expansion Clonal Expansion Plasma Cells T helper Cytotoxic B B T T T B B B Memory B Cells B B B T T T T Memory T Cells T T T The Link Between Innate and Adaptive Immunity The Antigen Presenting Cell (APC): Vital for activation of lymphocytes. Include macrophages, dendritic cells, and B lymphocytes. The antigen is taken up by phagocytosis by an APC (e.g. macrophage or a professional APC). These cells then migrate to lymphoid tissue to present antigen to the lymphocytes. The antigen is presented on the surface of the APC and shown to a T cell. If the T cell has the correct receptor to bind to the antigen the immune response will proceed. The Professional APCs: Dendritic Cells Sentinels of the Immune System Derived from bone marrow blood cell precursors. Reside in many tissues but can also circulate. Resident DCs often given special names dependent on their localization (e.g. langerhans cells of the skin). Often in close contact with the external environment where they search for antigen. Capable of migrating to lymph nodes where they have a chance to present their antigen to T cells. Dendritic Cells Langerhans Cells The Immune System as a Defence Organization 1) Its function is selective destruction. 2) It is large, complicated and elaborate. 3) It is expensive. 4) It is wasteful. 5) It has distinct components performing apparently identical functions. 6) It is slow to react. 7) It is prepared for events that never happen. 8) It fights today’s threats with the solutions of past problems. 9) It is susceptible to corruption. 10) It can destroy that which it protects. Parnham Nature 1990; 344;709-11 The Tissues of the Immune System The Tissues of the Immune System Primary Lymphoid Tissues - where immature lymphocytes acquire the capacity for antigen recognition. Bone marrow- T cell development, and B cell development and maturation Thymus- T cell maturation Secondary Lymphoid Tissues- Sites of lymphocyte activation Lymph nodes- Screens lymph Spleen- Screens blood borne antigens Mucosa Associated Lymphoid Tissue (MALT)- Screens mucosa Thymus A bilobed encapsulated organ located in the lower neck. Site of T cell maturation 1) acquisition of T cell immunocompetence 2) development of immunological self tolerance Once immunocompetent T cells have been selected they enter the circulation and migrate to other lymphoid organs. Thymus progenitor cells from bone marrow lobule cortex proliferation & cortex (Immature T cells) selection capsule medulla Mature T cells enter circulation medulla septa Thymus cortex capsule lymphoblasts mitotic cells macrophages Thymus adipose tissue Degeneration of the thymus in adults Secondary Lymphoid Organs Secondary Lymphoid Tissues- Sites where immune responses are carried out. Lymph nodes- Screens lymph Spleen- Screens blood borne antigens Mucosa Associated Lymphoid Tissue (MALT)- Screens mucosa Lymph Nodes Lymph Nodes Small organs found in groups or chains in sites where lymphatic vessels drain an anatomic region. They have two main functions: 1. Phagocytic cells within the nodes act as non specific filters of particulate matter e.g. carbon & micro-organisms, preventing them from reaching the general circulation. 2. Location where lymphocytes can interact with new antigens and APCs, which facilitates activation of an immune response. Lymph Nodes Structure Surrounded by a fibrocollagenous capsule from which trabeculae extend into the node forming a supportive network. The surface is penetrated by a number of afferent vessels which drain into the node leading to the hilum where the efferent vessels transport the lymph into the collecting vessels. The parenchyma consists of an extracellular matrix supporting regions of lymphocyte aggregates (follicles) where immune activation takes place. Lymph Nodes Lymph Nodes capsule subcapsular sinus cortex follicles paracortex medulla hilum Lymph Nodes Lymphoid follicle mantle germinal center Follicles- regions of B cell activation The germinal center consists of activated, dividing B cells, with a few T cells. The mantle zone is primarily resting B cells. T cells make up the majority of cells in the paracortex. Secondary Lymphoid Organs Secondary Lymphoid Tissues- Sites where immune responses are carried out. Lymph nodes- Screens lymph Spleen- Screens blood borne antigens Mucosa Associated Lymphoid Tissue (MALT)- Screens mucosa Spleen Responsible for immunological responses against blood antigens. Removes aged or defective blood cells. Haematopoietic organ in the embryo. Spleen Trabeculae Red Pulp White Pulp White Pulp Fibrous capsule Spleen Red PulpResponsible for filtering blood macrophages White PulpImmunological region of the organ Spleen mantle zone germinal center Splenic follicles similar in structure and function - to follicles of lymph nodes. Secondary Lymphoid Organs Secondary Lymphoid Tissues- Sites where immune responses are carried out. Lymph nodes- Screens lymph Spleen- Screens blood borne antigens Mucosa Associated Lymphoid Tissue (MALT)- Screens mucosa Mucosa Associated Lymphoid Tissue (MALT) Populations of immune cells in the mucosa of many epithelial tissues. They may be organized aggregations of immune cells or simply be a collection of scattered lymphocytes within the tissue. Functionally analogous to lymph nodes. Mucosa Associated Lymphoid Tissue follicle Peyer’s Patch (Gut Associated Lymphoid Tissue) Mucosa Associated Lymphoid Tissue Ileum Appendix Diffuse collection in the lamina propria Mucosa Associated Lymphoid Tissue Tonsil