Type IV hypersensitivity reactions Notes
Osmosis High-Yield Notes
This Osmosis High-Yield Note provides an overview of Type IV hypersensitivity reactions essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Type IV hypersensitivity reactions:
NOTES NOTES TYPE IV HYPERSENSITIVITY REACTIONS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Delayed, T cell-mediated (antibodyindependent) hypersensitivity reaction ▪ 24–72 hour delayed nature due to stepwise sensitization-response progression ▫ Antigen presentation by antigen presenting cells (APCs) → naive T-cells recognition → T-cells, macrophages migration, response Role of CD4+ (helper) T cells, macrophages ▪ CD4+ (helper) T cells ▫ APC displays antigen on MHC II receptor → naive CD4+ T cell binds MHC II via T cell receptor, CD4 coreceptor → T cell expresses CD28 → binds APC B7 → cobinding stimulates APC cytokine secretion ▫ Interleukin (IL) 12 produced → TH1 cell maturation → TH1 secrete IL-2, IFN𝛄 → proliferation of TH1 response, macrophage recruitment, activation ▫ IL-6, TGF-beta produced → TH17 cell maturation → TH17 secrete IL-17 → recruit neutrophils ▪ Macrophages ▫ Secrete TNF-alpha, IL-1, IL-6 → promote inﬂammation, leaky endothelium → edema, fever; secrete lysosomal enzymes, complement, and reactive oxygen species (ROS) → tissue damage ▪ Pathophysiology in inﬂammatory bowel disease (IBD), multiple sclerosis (MS), rheumatoid arthritis (RA) Role of CD8+ (AKA cytotoxic, effector, killer) T cells ▪ Altered host cell MHC I signal → CD8+ T cell receptor → activate CD8+ T cells 228 OSMOSIS.ORG ▪ Secrete perforins, granzymes → create membrane pores, induce cellular apoptosis ▪ Pathophysiology in Type I diabetes mellitus (DM), against islet cells; Hashimoto’s thyroiditis, against epithelial cells; immune response to some tumor cells Common Type IV hypersensitivity reactions ▪ Allergic contact dermatitis ▪ Mantoux test ▪ Diabetes mellitus type I ▪ Hashimoto’s thyroiditis ▪ Multiple sclerosis ▪ Coeliac disease ▪ Giant-cell arteritis ▪ Postorgasmic illness syndrome ▪ Reactive arthritis ▪ GVHD ▫ Transfusion-associated graft versus host disease TYPES Contact hypersensitivity ▪ Molecules covalently alter major histocompatibility complex (MHC) I receptors to neo-self antigens; nickel, urushiol (poison ivy molecule) Chronic, delayed hypersensitivity ▪ Agents unusually resistant to elimination by immune system; tuberculosis (TB), leprosy, silicosis, sarcoidosis COMPLICATIONS ▪ Granuloma formation in chronic, delayedtype hypersensitivity reactions ▪ Due to hyperactive macrophages, surrounding inﬂammatory reaction “walls off” offending agent (e.g. sarcoidosis, tuberculosis, silicosis)
Chapter 39 Type IV Hypersensitivity Reactions SIGNS & SYMPTOMS ▪ Local inﬂammatory reaction → erythema, warmth, edema, fever ▪ Sequelae of organ-speciﬁc cell destruction ▫ Islet cell destruction in pancreas → insulin-deﬁcient (e.g. lethargy, seizure, coma) ▪ Chronic inﬂammation → granuloma formation → organ failure DIAGNOSIS OTHER DIAGNOSTICS ▪ Exposure history of molecule/agent at site of symptoms ▪ Contact hypersensitivity ▫ Patch test (adhesive-mounted patches with miniscule amounts of allergen imbued in tape) ▫ Evaluate in 48–96 hours for local skin reaction ▪ Tuberculosis ▫ Tuberculin skin test (TST)/puriﬁed protein derivative (PPD) test ▫ Intradermal injection of tuberculin protein → pre-sensitized T-cells react to antigen → measure induration size at 48–72 hours ▫ Positive test (induration size) inversely related to TB exposure risk of individual TREATMENT MEDICATIONS ▪ Corticosteroids for inﬂammatory control ▫ Systemic for severe, generalized reactions; otherwise, site-speciﬁc (e.g. topical for contact dermatitis; inhaled for hypersensitivity pneumonitis) GRAFT-VERSUS-HOST DISEASE (GvHD) osms.it/graft-versus-host-disease PATHOLOGY & CAUSES ▪ Type of transplant rejection caused by immunocompetent, donor T cells reacting against recipient MHC I “foreign” antigens ▫ Variable time course of symptoms ▫ Common targets: skin, liver, intestine epithelial tissue ▪ Donor CD4+ T cell → recognize recipient MHC II as foreign → activated donor CD4+ T cells → cytokine release → recipient macrophage, CD4+ recruitment → exacerbate cytokine response ▫ Tumor necrosis factor (TNF) alpha: possible cause of “metabolic wasting” ▪ Donor CD8+ T cell → recognize recipient MHC I as foreign → activated CD8+ T cells → Fas, perforin-mediated cytotoxicity ▫ Majority of tissue destruction occurs via CD8+ T cells ▪ Similar graft-versus leukemia reaction (GvL) beneﬁcial in individuals with leukemia due to ability to help eliminate recipient’s hematopoietic cancer cell line RISK FACTORS ▪ Liver, bone marrow transplants (rich in lymphocytes) ▪ T cell immunodeﬁcient individuals, newborns OSMOSIS.ORG 229
SIGNS & SYMPTOMS ▪ Metabolic wasting/failure to thrive, maculopapular rash, jaundice, bloody diarrhea, hepatosplenomegaly DIAGNOSIS LAB RESULTS ▪ Histological analysis of easily biopsied tissue in individual with history of transplantation ▫ Liver, skin, gastrointestinal (GI) tract; most helpful in chronic, indolent disease OTHER DIAGNOSTICS ▪ Clinical presentation ▫ Constellation of symptoms TREATMENT MEDICATIONS ▪ Prophylaxis (e.g. cyclosporine, methotrexate) ▪ Site-directed corticosteroids ▫ Topical for primary skin manifestation; non-absorbable (e.g. budesonide, beclomethasone) for GI involvement Figure 39.1 A CT scan in the coronal plane of the abdomen of an individual with graftversus-host disease. The gastrointestinal tract, including the stomach and small bowel, is grossly edematous. OTHER INTERVENTIONS Prevention ▪ Proper donor, recipient human leukocyte antigen (HLA), MHC, minor histocompatibility (MiHA) matching; irradiation of transfused blood products Figure 39.1 A colonic biopsy taken from an individual with graft-versus-host disease. There is ﬂorid cryptitis (neutrophils inﬁltrating the crypt wall) and apoptotic debris at the crypt bases. 230 OSMOSIS.ORG
Osmosis High-Yield Notes
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