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
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 by visiting the associated Learn Page.