Type 4 Hypersensitivity and Chronic Inflammation

Type 4 Hypersensitivity Delayed Type Hypersensitivity (DTH) Sensitization phase →initial exposure triggers production of a T-cell (THI) cell response →takes 1-2 weeks time Intracellular bacteria 10-12 CD4T1 cel Tot cells (generally) APC Antigen presenting cells Dendritic cells Macrophages Langerhans cells D-mediating call CD4+T1 generally and T17, T2, and CD occasionally Effector phase Streted clusif Mambrane Sensitized Trell Resting macrophage Cytokines: FN-TNF 5-3, GM-CSP, VI MCP-110CL2 Astreated macrophage THF Effects of macrophaje sctisation thegousta expression TNF receptors Oxygenradicals Nitricoside Defens thermakines Secondary exposure brings about the DTH response →delay (ed) response happens in 24-72 hours →mediated primarily by Tul cytokines and macrophage Contact dermatitis Contact Dermatitis Sensitization can occur if a reactive chemical compound binds proteins, which are modified and then presented to T cells to skin Could be induced by cosmetics, pharmaceuticals, industrial chemicals, metal lans paison trs pobon cak • Can cause strong cell-mediated responses against skin cells, inducing blisterlike lesions and rashes Poison Ivy/Oak Sensitization can occur if a reactive chemical compound binds to skin proteins • Urushiol oxidation in skin allows it to bind to skin proteins Modfied proseins triken ap by DCs carried to regional lymph nods whare degraded and prosented on MHC dass I MHC class peptides induce T. formation T,I collis retum to skin, releaso cytokines that activate macrophages Macrophages release inflammatory cytolines, lytic enzymes, and ROS species causing tissue damage Urushiel ON OH (CH R-TH),CH-CH(CHCH -(CH),CH=CHCH, CH=CHOCH, CH, or R(CH), CH=CHCH,CH=CHCH=ORCH, and others Tuberculin Test The DTH reaction can be detected by a skin test by injecting a small amount of antigen under the skin Ifa red, slightly swollen, firm lesion develops in 48- 72 hours, the test is positive A positive cast indicates that che individual fuas population of sensitized TH1 cellt against the antigen, bur does NOT indicate if an active infection a ocurring or if the individual already overcamo an infection (icaring mamery cells) For this reason, the Th vaccine is sat commanly administered in the United Stratos (it would Inad to finc positiver 48-72 hours infectious causest Chronic Inflammation Noninfectious casses: Hyperglyamia/cbesity Aummae responses -Allergic responses Unresolved infection Intestinal microbes Chrenic inflamonation Organ transplantation Cancer Inflammation doesn't always resolve in a short period of time; it may last indefinitely, contributing to numerous other problems • Infectious conditions can lead to tissue damage (gum disease, ongoing infection due to inappropriate clearance) • Physical damage to tissues can release DAMPs that induce inflammatory mediators (CTE?) 14TN-1818-188-17. other inflammatory mediators Tissue changes: Call death Scarring (fibrosis) Blood weesal growth (angiogenesis) Call proliferation Metabolic changes pirin signaling Obesity Type 2 diabetes • Obesity can result in a chronic inflammation due to visceral adipocyte stimulation to release inflammatory cytokines (TNFa, IL-6) Diabetes can result in chronic inflammation as a consequence of inflammatory cytokines inhibiting downstream events at the insulin receptor Other systemicconditions: Heart disease and atherosclerosis Organ failure kidney, heart, livari Cancer Alzheimer's Autoimmune diseases Autoinfammatory diseases Inflammatory bowel diseases Allergic conditions, asthma Organ transplant rejection • Cytokines released during chronic inflammation can induce widespread tissue scarring leading to organ dysfunction contributing to tumor development Genetica