inflamation part 4 Flashcards
Chronic inflammation
in comparison with acute inflammation, chronic inflammation tends to be gradual in onset, of relatively lower intensity, longer lasting.
components: lymphocyte, plasma cell, macrophage (mononuclear cell) infiltration: tissue destruction b y inflammatory cells. Repair with fibrosis and angiogenesis (new vessel formation)
Causes of chronic inflammation
persistent injury or infection: ulcer, tuberculosis.
prolonged exposure to a toxic agent: pulmonary silicosis (silica in the lung)
autoimmune disease: self perpetuating immune reaction that results in tissue damage and inflammation: rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis.
Cell and mediators of chronic inflammation
the characteristic inflammatory cells are mononuclear cells, especially lyphocytes and or macrophages. Eosinophils and or plasma cells may be present. Tissue destruction is a hall mark of chronic inflammation.
Macrophage pathways
there are two major pathways of macrophage activation, called classical and alternative. The stimuli that activate macrophages by these pathways, and the function of the activated cells, are quite different. Several function of macrophages are central to the development and persistnce of chronic inflammation and the accompanying tissue injury. The products of activated macrophages eliminate injurious agents such as microbes and initiate the process of repair, but are also responsibel for much of the tissue injury in chronic inflammation.
Classical: IFN gammaa.Microbicidial actiona: phagocytosis and killing of many bacteria and fungi. Inflammation
Alternative pathway: IL-13 and il4. Tissue repair, fibrosis. Antiinflammatory effects.
lymphocytes
microbes and other environmental antigens activate T and B lymphocytes, which amplify and propagate chronic inflammation.
granulamatous inflammatio
pattern of chronic inflammation induced by T cell and macrophage activation in response to an agent that is resistant to eradication. it is characterized bny collections of activate dmacrophages, often with T lymphocytes and sometimes associated with central necrosis. The activated macrophages may develop abundant cytoplasm and ebgin resmmble epithelial cells, and are called epithelioid cells. Some activated macrophages amy fuse, forming multinucleate giants cells. It is mediated by cytokines produced by macrophages and lymphocytes (notably T lymphocytes.
Foreign body giant cell
are incited by relatively inert foreign bodies, in the absence of T cell mediated immune responses typically foreign, body granulomas around materials such as talc (associated with intravenous drug abuse), sutures, or other fibers that are large enough to preclude phagocytosis by a macrophage and do not incite any specific inflammatory or immune response. Epithelioid cells and giant cells are opposed to the surface of the foreign body. The foreign material can usually be identified in the center of the granuloma particularly if viewed with polarized light, in which it appears retractile.
immune granulomas
caused by a variety of agents that are capable of inducing a persistent T cell mediated immune response. This type of immune response produces granulomas usually when the incitng agent is diffuclt to eradicate, such as ta persistent mcirobe or a self antigen. in such responses, macrophages activate T cells to rpoduce cytokines, suhc as IL2 which activates other T cells, perpetuating the response, and IFN gamma, which activates the macrophages. It is not established which macrophage activating cytokines (IL4 or IFN gamma) transform the cells into epithelioid cells and multinucleate giant cells.
Caseuous necrosis
coagulative and liquifactive center: TB and fungal infecitons
noncaseating granulomas
reaction to foreign material (talc or susture), chron’s disease and cat scratch disease.
non specific indicators of inflammation: left shift
a peripheral blood msear is examined and the percentage of each type of WBC is determined. Some of the neutrophils may show immature types “bands” the immediate precursors of mature neutrophils. The number/percentage of immature neutrophils ins increased in certain infections, notably bacterial infections. When the number of immature neutorphils and especially, if even less mature types are present in the peripheral smear. Leukmoid reaction
non specific indicators of inflammation: erythrocyte sedimentation rate
the rate at which RBCS “settle” to the bottom of a tube is determiend by the amount of protein in the blood. This, in turn, is largely detremined by the amount of fibrinogen. The amount of firbinogen in the blood, and erythrocyte sedimentation rate (SER), are increased non specifically in patients who are undergoing an inflammatory responses.
non specific indicators of inflammation: C reactive protein
blood levels of this glycoprotein are non specifically elevated in patients who are undergoing an inflammatory response. It is synthesized by the liver.
Fever
Characterized by an elevation of body temperature, usually b 1 degree to 4 degree, is one of the most prominent manifestations of the acute phase response, especially when inflammation is associated with infection. Substances that induce fever are called pyrogens. The increase in body temperature is caused by prostaglandins that are produced in the vascular and perivascular cells of the hypothalamus. Bacterial products such as LPS stimulate leukocytes to release cytokines such as IL1 and TNF that increases the enzyme that convert AA into prostaglandins. In the hypothalamus, the prostaglandins, PGE2, stimulat ehte rpdocution of neurotransmitters that reset the temperature set point at a higher level. NSAIDs, inclduing aspirin, reduce fever by inhibiting prostaglandin synthesis. An elevated body temperature has been shown to help amphibians ward off microbial infections, and it is assumed that fever is a protective host response in mamal as well, although the mechanisms is unknown. One hypothesis is that fever may induce heat shock proteins that enhance lymphocyte responses to microbial antigens.
TNF
source; macrophages, mast cells, T lymphocytes
stimulates expression of endothelial adhesion molecules and secretion of other cytokines systemic effects
