Presentation on theme: "Inflammation 1.Inflammation: local defensive response resulted by damage to body tissue. 1.Causative agents: microbial infection physical agents (heat,"— Presentation transcript:
Inflammation 1.Inflammation: local defensive response resulted by damage to body tissue. 1.Causative agents: microbial infection physical agents (heat, radiant agents, electricity, and sharp objectives) chemical agents (acids, basis, and gases). 2.Signs: redness pain heat swelling 3. (and sometimes) loss of function.
Inflammation 3.Functions of inflammation: To destroy the injurious agent, if possible, and to remove it and its by-products from the body. If destruction is not possible, to limit the effects on the body by confining or walling off the injurious agent and it's by products. To repair or replace tissue damaged by the injurious agent and it's by products.
Inflammation 4.Stages of infection: A.Vasodilatation and increase permeability of blood vessels: this is caused by chemical released by cells of damaged tissue listed in table (3-1) ChemicalProduced byFunction 1 Histamine mast cell basophiles platelets Vasodilatation 2 Kinins By liver and present in blood plasma Vasodilatation, Chemotaxis for granulocytes 3 Prostaglandi ns Cells of damaged area Vasodilatation, help phagocytes move through capillary wall. 4 Leukotrienes mast cell of (skin, respiratory system, blood vessels) basophiles Increase permeability of blood vessels, help attack phagocytes to pathogen 5 Cytokines: IL-1, IL-6, IL-8, IL-12, and TNF-α Macrophages (fig. 3-1) Vasodilatation, increase permeability of blood vessels, Chemotactic factors
Activates vascular endothelium, activates lymphocytes, local tissue destruction, increase access of effector cells Local effects Activates vascular endothelium, and increase vascular permeability which leads to increase entry of IgG, complement and cells to tissue and increase fluid drainage to lymph nods Chemotactic factor recruits neutrophils, basophile and T cells to site of infection Lymphocyte activation, increase antibody production Activates NK cells induces the differentiation of CD4 T cells into T H1 Systemic effects Fever Production of IL-6 Fever, Moblization of metabolite shoks Fever, induce acute- phase protein production Activated macrophages secret a range of cytokines
Inflammation B.Phagocyte migration and phagocytosis: PMNs and monocytes leave the blood and migrate to sites of infection in a multistep process mediated through adhesive interactions that are regulated by macrophage-derived cytokines and chemokines. 1.The first step (Rolling adhesion) involves the binding of leukocytes to vascular endothelium through interactions between E-selectins on the endothelium and their carbohydrate ligands on the leukocyte sialyl-Lewis X moiety (s-Le X )
Inflammation 2.The Tight binding does, however, allow stronger interactions, which occur as a result of the induction of intercellular adhesion molecules ICAM-1 on the endothelium and the activation of its receptors leukocyte functional antigens LFA-1 on the leukocyte by contact with a chemokine like IL-8and its receptor. 3.This binding allows the leukocyte to squeeze between the endothelial cells forming the wall of the blood vessel leading to diapedesis and migration toward the source of chemokines.
Inflammation 4.The invading microbes were eliminated by phagocytosis of PMNs other phagocytes start establishes for adaptive immune response. 5.The pain is caused by nerve damage pressure of edema irritation by toxins.
Inflammation 3.Tissue repair: the process in which tissue replace dead or damaged tissue. 1. Skin has a high capacity for regeneration, whereas, cardio muscular does not. 2.Some microbes evade phagocytosis and cause chronic inflammation like Mycobacterium tuberculosis, such away lead to continuous production of cytokines and induce fibroblast in the site of infection to synthesis collagen fiber which leads to fibrosis.
Fever Fever : abnormally high body temperature 1.The most causes of fever are bacteria, toxin, and viruses. 2.Bacterial endotoxin (LPS) bound to CD14 on macrophage. This then triggers the membrane protein Toll Like Receptor 4 (TLR4) to signal to the nucleus, activating the transcription factor, which in turn activates genes involved in production cytokines IL- 1(endogenous pyrogen) and TNF-α 3.These cytokines cause the hypothalamus to release prostaglandin that reset the hypothalamic thermostat at high temperature, thereby causing fever.
Fever 4.A high body temperature is caused by constriction of blood vessels, increase rate of metabolism, and shivering. 5.Fever is considered defense against disease according to: IL-1 helps to activate T-cells and so on adaptive immunity. High body temperature intensifies the effect of antiviral interferon. Increase production of transferrins that decrease the iron availability to microbes. High body temperatures increase speed of body reactions and help tissue repair.
Antimicrobial substances Antimicrobial substances: Complement system. Complement is a system of more than 30 plasma proteins that activates a cascade of proteolytic reactions on microbial surfaces but not on host cells, coating these surfaces with fragments that are recognized and bound by phagocytic receptors on macrophages. The cascade of reactions also releases small peptides that contribute to inflammation and cytolysis (fig. 3-3).
Complement Complement activation can occur on three pathways according to activation manner: A.Classical pathway: this pathway is initiated by an antigen-antibody reaction. The splitting of C3 into C3a and C3b starts a cascade that result in cytolysis, inflammation, and opsonization. (fig 3-4)
Complement B.Alternative pathway: this pathway is activated by contact between certain complement protein (C3 and factors B, D, and P) and pathogen there are no antibody involved. Once C3a and C3b are formed they participate in cytolysis, inflammation, and opsonization. (fig 3-5)
Complement C.Lectin pathway: when the plasma protein mannose- binding lectin (MBL) binds to mannose sugar on the surface of microbes. MBL function as an opsonin that enhance phagocytosis and splitting of C3 into C3a and C3b starts a cascade that result in cytolysis, inflammation, and opsonization. (fig 3-6)