introduction to immunity & Innate immunity.ppt
- 2. Learning Objectives Define immunity and its types and innate immunity Classify types of immunity according to their function especially innate immunity List the components of immune system Discuss the functions of immune system Discuss the role of T cells, B cells, natural killer cells, macrophages in immunity Discuss the specificity of the immune response and properties, component and pattern of recognition receptors Discuss properties, components & pattern recognition receptors.
- 3. 1.1. Definition of terms Immunology The study of immune system or immunity the study of all aspects of host defense against infection and of adverse consequences of immune responses. The study of the physiological mechanisms which enable the body to recognize materials as foreign and to neutralize, metabolize or eliminate them without injury to the host tissue.
- 4. Immunity: State of protection from infectious diseases OR Defined as resistance to disease specifically infectious disease. Immune system: the collection of cells, tissues and molecules that mediate resistance to infections.
- 5. How do these specific protective mechanisms originate? The process by which these host defenses originate can be summarized by three actions: (1) the recognition of the foreign organism by specific immune cells, (2) the activation of these immune cells to produce a specific response (e.g., antibodies), (3) the response that specifically targets the organism for destruction.
- 7. Innate immunity Innate immunity (also called natural, or native, immunity) refers to intrinsic mechanisms that are poised to react immediately, and thus constitute the first line of defense. Mediated by cells and molecules that recognize products of microbes and dead cells and induce rapid protective host reactions.
- 8. Innate immunity: Properties Non – specific i.e., same response to the range of pathogens Always present, ready to provide immediate defense has no memory i.e., same response after repeated exposure Relies on already formed components Based on genetic makeup
- 9. Innate immunity: Functions 1. Initial most response to microbes 2. Eliminate damaged cells and initiate the process of tissue repair 3. Stimulates adaptive immune response
- 10. Innate immunity: Components Physical (Epithelial barrier) Cellular mechanisms {phagocytic cells (mainly neutrophils and macrophages), dendritic cells, natural killer cells etc.} Humoral mechanisms {antibodies, complement proteins, antimicrobial peptides etc.}
- 11. Lines of defenses in immune system Innate defense system has two lines of defense First - external body membranes (skin and mucosae) Second - antimicrobial proteins, phagocytes, and other cells Inhibit spread of invaders Inflammation most important mechanism Adaptive defense system Third line of defense attacks particular foreign substances Takes longer to react than innate system
- 12. Prevent entrance: Structural barriers – effective with most microorganisms Skin - epidermis = layers of tightly packed epithelial cells. Outer layer is dead cells and keratin, waterproofing protein Inner layer skin - dermis = blood vessels, hair follicles, sweat glands, and sebaceous glands that produce an oily secretion called sebum Cilia and cough reflex – helps expel microbe containing mucous Sneeze Innate Defense: Physical barriers
- 13. Mucus membranes - conjunctivae, alimentary, respiratory, and urogenital tracts • saliva, tears, and mucous secretions wash away invaders and contain antibacterial or antiviral substances. • acidity (pH 5.6) of sweat, sebaceous glands, vagina (pH 5) and stomach (pH 1) – unfriendly to many microorganisms enzymes present in the skin and stomach, tears Normal flora - out compete pathogens for attachment sites on the epithelial cell surface and for necessary nutrients. Innate Defense: Physical barriers
- 14. Innate Defense: Cellular & Humoral mechanisms To prevent expansion of penetration Recognize carbohydrates not normally present on cells such as mannose May cause nonspecific activation of white cells Phagocytosis – by neutrophils, eosinophils, basophils, or macrophages, mast cells, and dendritic cells Clotting mechanism which entraps organisms in fibrin clots Complement System can lyse cells or enhance phagocytosis
- 15. Phagocytes: engulf bacteria, release toxic chemicals, present antigens Residue is exocytosed Phagolysosome destroys infectious agent Phagosome Lysosome Macrophage Infectious agent engulfed Neutrophil, macrophage, eosinophil: Phagocytic cells Originally WBCs – they migrate into connective tissue The “clean-up crew”: phagocytose debris and digest via lysosomes Neutrophils enter first then macrophages (derived from monocytes) Eosinophils involved with parasitic infections and Ag-Ab complexes Also an APC
- 17. How do phagocytes invade the area of infection or injury? - Inflammatory factors – released by mast cells, etc. - Vasodilation – capillaries become permeable - Margination – WBCs slow down & align on the vessel wall -Diapedesis – blood cells leave vessels & enter the CT -Chemotaxis – blood cells follow a chemical gradient (move toward the source ie., bacteria)
- 19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (b) Venule Eicosanoids Histamine Basophil Arteriole Basophil and mast cell: Proinflammatory chemical-secreting cells Heparin Vasodilation Increases capillary permeability Capillary Anticoagulant Increases inflamation Basophils open up vessels & increase blood flow
- 20. Eosinophils: Parasite-Destroying Cells Eosinophil Parasitic worm Cytotoxic chemicals Eosinophils: Parasite-destroying cells (d) Eosinophils also phagocytose antigen-antibody complexes
- 22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Recognizes unhealthy cell (usually expressing abnormal proteins or viral proteins – uses perforins (make a hole in the membrane) and granzymes; cells that lack "self" cell-surface receptor Induce apoptosis in cancer cells and virus-infected cells Apoptosis Unhealthy or unwanted cell NK cell Granzymes enter pore, causing apoptosis of cell Perforin forms a transmembrane pore Perforin and granzyme NK cell: Apoptosis-initiating cells Immunological surveillance: NK cells
- 23. Complement Proteins C C Elimination of immune complexes Antigen Antibody Complement Erythrocyte Complement (C) cross-links immune (antigen-antibody) complexes to erythrocyte and transports to liver and spleen. Complement proteins create MAC to lyse cell. Complement activates and attracts various cells of innate immunity. Complement (C) binds to pathogen; acts as opsonin Macrophage Pathogen Complement Inflammation Opsonization Cytolysis Complement MAC protein Pathogen Inflammation Macrophage Neutrophil Basophil Mast cell A series of ~20 enzymes normally circulating in an inactive form • May be activated by the classical or alternate pathways • Can result in lysis or enhanced phagocytosis of cells Thus, helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism.
- 24. Binds receptors of neighboring cells: Promotes macrophage function and apoptosis of infected cell Triggers synthesis of enzymes destroying viral RNA or DNA Triggers synthesis of enzymes that inhibit synthesis of viral proteins Interferons – signaling molecule (cytokine) released by viral-infected cells
- 25. Reactions of Innate Immunity The innate immune system provides host defense by two main reactions. 1. Inflammation. 2. Antiviral defense.
- 26. Reactions of Innate Immunity: Inflammation Overall non-specific reaction of body to injury or invasion – starts immediately with infection or trauma Reactants may initiate, expand, or sustain the response Can be acute (short duration) or become chronic (prolonged duration) Has 4 cardinal signs: heat, pain, redness, loss of function.
- 27. Reactions of Innate Immunity: Antiviral defense Type I interferons produced in response to viruses act on infected and uninfected cells and activate enzymes that degrade viral nucleic acids and inhibit viral replication, inducing what has been called an antiviral state. NK cells recognize virus-infected cells
- 28. Reactions of Innate Immunity: Antiviral defense
- 30. Microbial pattern recognition by innate immunity Cells that participate in innate immunity are capable of recognizing components shared by microbes and molecules released by injured and necrotic cells through their pattern recognition receptors (PRR).
- 31. Microbial pattern recognition by innate immunity
- 32. Pattern recognition receptors (PRR) expressed mainly By immune cells such as dendritic cells, macrophages, monocytes, neutrophils, as well as By non-immune cells e.g., Epithelial cells Function of pattern recognition receptors (PRR) 1. Opsonization 2. Phagocytosis 3. Activation of complement 4. Activation of proinflammatory pathways 5. Induction of apoptosis
- 33. Location of pattern recognition receptors (PRR) Plasma membrane receptors detect extracellular microbes, Endosomal receptors detect ingested microbes, and Cytosolic receptors detect microbes in the cytoplasm
- 34. Classes of Pattern recognition receptors (PRR) 1. Extracellular PRR (Binding activate proinflamm. Activity) Toll-like receptors (TLRs) C-type lectin receptors (CLRs) 2. Endosomal PRR (Mediate microbial uptake by phagocytes) Toll-like receptors (TLRs) 3. Cytosolic PRR (Activate complement proteins) NOD-like receptors (NLRs) and the inflammasome RIG-I-like receptors (RLRs)
- 35. Thank you