Immune System 1 PDF

Immune system 1 Dr Mouhamed Alsaqati Stage 1 [email protected]  Learning objectives Learn the basic concepts of immunology Define cells and tissue of the immune system Understand the mechanisms and functions of the...

Immune system 1 Dr Mouhamed Alsaqati Stage 1 [email protected]  Learning objectives Learn the basic concepts of immunology Define cells and tissue of the immune system Understand the mechanisms and functions of the innate immune system What is Immunology? - Definitions “The study of physiological mechanisms that humans and other animals use to defend their bodies from invasion by all sorts of other organisms” The whole of the cells dedicated to the defence collectively form the immune system The immune system is crucial to human survival. In the absence of a working immune system, even minor infections can be fatal! To provide immunity that will give protection from a disease, the immuno- system must first battle with the microorganism An immunogen is a molecule that stimulates the immune system to produce a response An antigen is the part of the immunogen that reacts with immune effector cells or soluble antibodies An epitope is the part of the antigen that reacts with immune effector cells or soluble antibodies  Pathogens Any organism with a potential to cause a disease is a pathogen 4 main types Bacteria Viruses Fungi Parasites i.e warms The immune system in the blood Red blood cells Plasma White blood cells (leukocytes) Platelets Haematopoiesis Myeloid cells classification 1) Granulocytes Neutrophil Eosinophil Basophil 2) Antigen presenting cells Monocytes Macrophages Dendritic cells 3) Mast cells Lymphoid cells classification 1) Small lymphocytes B cells T cells 2) Large lymphocytes NK cells Lymphoid organs Primary Bone marrow Thymus Secondary Spleen Adenoids Tonsils Appendix Lymph nodes Primary lymphoid tissues Bone marrow It is the soft spongy, highly cellular tissue that fills the internal cavity of bones B cells originate and mature in it T cells originate in it, but leave at an immature stage Thymus It is located just above the heart Immature T cells migrate in thymus to complete their maturation As they differentiate, T cells progress from the cortex into the medulla ! In primary lymphoid tissues, lymphocytes are only produced and matured Immune-responses do not take place here Secondary lymphoid tissues Sites where mature lymphocytes are activated to respond to invading pathogens Lymphatic vessels originate in the connective tissues throughout the body where they collect the plasma fluid that continually leaks out from blood vessels Lymph nodes lie at the junctions of a network of lymphatic vessels This fluid, called lymph, is returned to the blood vessels via the thoracic duct Circulating lymphocytes can move from blood capillaries to lymph nodes where they can eventually meet a pathogen Secondary lymphoid tissues - Lymph nodes Arriving lymphocytes segregate in different areas of the lymph node During an infection pathogens are drained in lymph nodes from the afferent lymphatic vessels where they are trapped by dendritic cells and macrophages B and T cells “meet” the pathogen and are activated, undergo clonal expansion and differentiation As the lymphocytes grow in number, the lymph node increases in size (swollen glands) Other secondary lymphoid tissues MALT (Mucosa Associated Lymphoid Tissue) are specialised lymphatic tissues that are distributed in submucosal layers of the gastrointestinal, genital, respiratory and urinary tracts i.e. tonsils and adenoids, bronchus associated lymphatic tissues, Peyer's patches, appendix and isolated follicles in intestinal mucosae Peyer’s patch in the intestine  2 types of immunity Innate immunity Adaptive immunity Rapid response (hours) No Slow response (days to weeks) memory Memory Fixed Variable Limited specificity Highly specific Constant during response Improve during response Cells of innate immunity vs cells of adaptive immunity macrophages NK cells Many locations, move around lymphatic system (specialised antigen presenting cells)  Phases of the immune response INNATE IMMUNITY 18 Immediate innate immune response Barriers Antimicrobial peptides Complement system Physical and chemical barriers Anti-microbial peptides  Complement system Group of nearly 30 serum and membrane proteins Act in an orderly sequence Have initial activation -> highly regulated enzymatic cascade Roles 1) Some activated proteins bind covalently to bacteria (opsonin) Bacteria are then phagocytosed by cells with complement receptors Complement system Classical pathway C1q C1r C1s Both antibody dependent/independent C4b opsonin Alternative pathway Both classical pathway dependent/completely independent C3b opsonin C3a/C5a pro-inflammatory MAC complex  Complement system Group of nearly 30 serum and membrane proteins Act in concert in an orderly sequence Have initial activation -> highly regulated enzymatic cascade Roles 1) Some activated proteins bind covalently to bacteria (opsonin) Bacteria are then phagocytosed by cells with complement receptors 2) Some small fragments (C3a and C5a) of complement recruit phagocytes to the site and regulate the inflammatory response 3) Some products activate B cells 4) Terminal component of system generates Membrane Attack Complex (MAC), which causes the Lysis of pathogen  Phases of the immune response INNATE IMMUNITY 18 Induced innate immune response Phagocytosis Cytokines production and inflammation Toll Like Receptors activation NK cells  Phagocytosis From the Greek word “phago” (I eat)  Main phagocytic cells: i) Neutrophils short-lived cells  multi-lobed nucleus (polymorphonuclear (PMN) cell)  abundant in sites of acute inflammation ii) Mononuclear phagocytes (monocytes and macrophages)  blood monocytes, alveolar macrophages etc.  Longer lived cells  Also Antigen Presenting Cells  Removal of the offending agents (Phagocytosis) Recognition and attachment Different types of receptors Opsonin receptors: the efficiency of phagocytosis is greatly enhanced when the microbe is coated with opsonin proteins for which the phagocytes express high-affinity receptors. The major C3b fragment of the complement and C4b Engulfment After a particle is bound to phagocyte receptors, the plasma membrane form a vesicle (phagosome) that encloses the particle. The phagosome then fuses with a lysosomal granule Killing and degradation Lysosomal enzymes (e.g. elastase, lysozyme and many more)  Cytokines production Low molecular weight proteins - (5-25kDa) secreted by cells that stimulate or inhibit the activity, proliferation or differentiations of other cells Around 20 Cytokines - include sub groups interferons, lymphokines, interleukins, chemokines 1. Mediators and regulators of innate immunity – Produced mainly by mononuclear phagocytes (neutrophils and macrophages) in response to infectious agent 2. Mediators and regulators of adaptive immunity – Produced mainly by T lymphocytes in response to specific recognition of foreign antigens 3. Stimulators of haematopoiesis – Produced by bone marrow stromal cells, leukocytes and other cells and stimulate the growth and differentiation of immature leukocytes Cytokines produced by macrophages Lots of effects!!! IL-1, IL-6, TNF induce fever to decrease bacterial/viral replication They induce a state of inflammation at the site of the infection  Inflammation -overview Features of inflammation Vasodilatation Increased vascular permeability Leukocyte migration Aim to bring immune cells in the location of the infection  Summary The immune system- cells, tissues & function Immediate innate immune response Barriers Antimicrobial peptides Complement system Induced innate immune response Phagocytosis Cytokines