Innate Immunity 2 PDF

Innate Immunity By: Dr. Iman Hussein Shehata Professor of Medical Microbiology and Immunology  By the end of this lesson the student is expected to: 1- List different components of innate immunity. 2- Discuss the role of mechanical and chemical barriers in inna...

Innate Immunity By: Dr. Iman Hussein Shehata Professor of Medical Microbiology and Immunology  By the end of this lesson the student is expected to: 1- List different components of innate immunity. 2- Discuss the role of mechanical and chemical barriers in innate immunity. 3- Discus mechanisms by which normal bacterial flora suppress the growth of pathogenic bacteria and fungi. 4- Enumerate phagocytic cells and describe steps and outcome of phagocytosis. 6- Describe mechanism of extracellular killing. 7- List circulating effector proteins in innate immunity and describe the function of each one. 8- Describe the events and the major purpose of inflammation  Extracellular Killing 1- Natural killer cells Performs Extracellular killing to get rid of large particles that cannot be phagocytosed by phagocytic cells as virus infected cells and malignant cells. NK cells are large granular lymphocytes that can perform extracellular killing as part of innate immune response efficiently. NK cells express two surface markers ;CD 16, CD 56  The activation of NK cells is determined by a balance between engagement of activating and inhibitory receptors expressed on the surface of NK cells. The activating receptors recognize Stress molecules which are cell surface molecules expressed on cells infected with viruses and intracellular bacteria, and cells and malignant cells The inhibitory receptors recognize the self-molecule : Class I MHC molecules. They block signaling by activating receptors Class I MHC expression protects healthy cells from destruction by NK cells In other words NK cells recognize cells that don’t express self- molecules or express altered self molecules as malignant cells or cells infected with viruses, intracellular bacteris Once activated NK cells release the content of their granules into the space between the two cells (target cell and natural killer) These granules contain perforins and granzymes forming transmembrane pores in the target cell followed by cell death NK cells also secrete effector proteins ( cytokines) during infection as interferon gamma which activates macrophages  5-Circulating effector proteins a. Complement system: The complement system is a group of soluble plasma proteins circulating in an inactive form Complement proteins can be activated by microbial surfaces or when foreign substances are complexed with antibodies  Effects of complement activation Once activated, complement leads to 1- Inflammation : Degranulation of mast cells and basophils. Release of the contents of granules leads to increased vascular permeability and recruitment of phagocytic cells 2- Enhance phagocytosis = Opsonization (act as an opsonin) is the process in which a microorganism (or other particulate material) is rendered more susceptible to phagocytosis by coating with an opsonin, a blood serum protein such as a complement component or antibody. 3- Direct lysis of bacteria Effects of Complement Activation  b- Cytokines Cytokines are small regulatory proteins that are produced in response to microbes and other antigens Cytokines allow for communication between cells to trigger the function of immune system against pathogens or tumors They are involved in all aspects of innate and adaptive immune responses as cellular growth, differentiation, inflammation and repair In response to injury, cells of immune system secrete several cytokines into the blood stream. Examples of these cytokines are interleukin 1, interleukin 6, tumor necrosis factor alpha (TNF α) and interferons.  Cytokines initiate their action by binding to specific membrane receptors on target cells cells of origin (autocrine), nearby cells (Paracrine) or cells at distant sites (endocrine) Extended Modular Program 14  Common features of cytokines Pleiotropic: a particular cytokine can act on different types of cells Redundant: the ability of a number of different cytokines to carry out the same function. Two cytokines may have synergistic or antagonistic effects Three major clasess; Mediators and regulators of innate immunity as interleukin 1, interleukin 6, tumor necrosis factor alpha (TNF α) and interferons. Mediators and regulators of adaptive immunity Stimulators of hematopoiesis e.g., Colony stimulating factors Extended Modular Program 15 Extended Modular Program 16  Properties of cytokines Pleiotropic: a particular cytokine can act on different types of cells Redundant: the ability of several different cytokines to carry out the same function. Two cytokines may have synergistic or antagonistic effects Extended Modular Program 17  Interferons (Antiviral Cytokines) Two types ❑ Type I Interferons (Interferon α and interferon β) are glycoproteins secreted early by viral infected cells and leukocytes to provide immunity to themselves and adjacent cells (induce an antiviral state) They constitute an important antiviral innate immune response against both RNA and DNA viruses by: Inhibiting viral protein synthesis and thus replication by downregulating protein synthesis in the infected cell upregulating MHC expression to facilitate recognition of infected cells. activate NK cells ❑Type II Interferons (interferon γ) which is secreted by natural killer cells to activates macrophages. Antiviral action of interferon  c- Acute phase proteins: Liver responds to cytokines released by activated immune cells as macrophages by producing acute-phase proteins as C- reactive protein and mannose binding proteins. These proteins can enhance phagocytosis (opsonins) and stimulate complement activation  Inflammation The inflammatory response is an innate immune reaction during which cells of the immune system and their active products are concentrated at the site of infection or tissue damage. The inflammatory response aids to eradicate infectious agents  Three major events occur: 1- Vasodilatation to increase local blood supply to the site of infection or injury allowing involvement of more cells of the immune system. 2- Increased capillary permeability to allow migration of white blood cells to the affected tissues. 3- Migration of white blood cells from capillaries into the affected tissue.  During the acute inflammatory response, pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α are produced. These cytokines have multiple local and systemic inflammatory effects. Local effect :TNF and IL-1 act on leukocytes and endothelium to induce acute inflammation, ❑ Systemic effects on the tissues, including ❑ Fever ( act on hypothalamus in thebrain) ❑ production of acute phase proteins by the liver ❑ Leukocytosis( increase production of leukocytes by the bone marrow ❑ Also, IL-8 (Chemokine) is produced which recruits neutrophils to the site of infection 26 Action of proinflammatory cytokines Extended Modular Program 27  Local and systemic actions of cytokines in inflammation Systemic TNF can cause the pathologic abnormalities that lead to septic shock, including decreased cardiac function, thrombosis, capillary leak, and metabolic abnormalities due to insulin resistance Extended Modular Program 28  However acute inflammation has harmful effects. Swelling may have a mechanical effect – for example, in acute epiglottitis where the airway may become obstructed by the swollen epiglottis. Inflammation also contributes to tissue damage. When acute inflammation fails to resolve, chronic inflammation occurs leading to tissue damage, which may end in fibrosis, scarring and loss of tissue function Thank You