Type IV hypersensitivity

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Delayed type hypersensitivity, Type IV

T cell mediated hypersensitivity reaction occuring more then 24 hrs after contact with the antigen

Delayed type hypersensitivity characeristics

an influx of nonspecific inflammatory cells, mostly macrophages into tissues. Lacks antibody involvement

DTH response

not always detrimental - but can cause extensive tissue damage and plays an important role in host defense against intracellular pahtogens and contact antigens

causative agents of type IV hypersensitivity rxn

bacteria, fungi, protozoa, noninfectious agents (chemicals)

transfer of DTH rxn

cannot be transferred via serum, only by T lymphocytes

sensitization phase of DTH

1-2 wks after primary contact with antigen

peptide epitopes and MHC class II proteins, CD4+ T cells associate to result in

a ell mediated response and the generation of memory Tdth cells

PPD

purified protein derivative, results in activation nof memory Th1 cells by APC and intiation of DTH

activated Tdth cells

secrete cytokines that result in vasodilation, increased vascular permeability, and recruitment/activation of macrophages

neutrophil appearence

early, 6-12 hrs

blood monocyte and T cell appearence

24-48 hrs after antigen exposure

crucial cytokines

TNF-alpha, IFN-y, MCF, MIF, IL-1, TNF-beta

tissue damage in DTH

results from release of hydrolytic enzymes and reactive oxygen intermediates from macrophages

the most important clinical form of DTH

granulomatous hypersensitivity

granulomas formation due to

1. persistance of particles in macrophage, 2. persistant immune complexes, 3. chronic irritants

ACD

allergic contact dermatitis, a T cell mediated eczematous disease

ACD characterized by

48-72 hr delayed eczematous response to the epicutaneous application of the antigen

ACD sensitization phase

10-14 days, haptens form complexes with skin proteins

epidermal langerhans cells

modified self proteins in ACD internalized by these cell and then migrate as veiled cell to regional lymph nodes

veiled cells produce

in the lumph node present to CD4+ and form memory CD4+ Th1 cells

Tdth

Th1 cell

elicitation phase

occurs with 48-72 hrs, activation of the Tdth cells and cytokines

CD8+ T cells role

contribute to tissue damage by cell-mediated cytotoxicity

lipid soluable chemicals

can cross the cell membrane and modify intracellular proteins

lesion

acute and chronic eczematous rxn observed in a hairless area

DDX of DTH

patch testing, positive test = local erythema and vesiculation

poison ivy exposure

oils (urushiol) leads to rash within 12-48hr and persists 2-4wks

pentadecacatechol

lipid soluable hapten, formed intermediate of urushiol

poison ivy lesion origin

lysis of altered epidermal cells by CD8+ T cells and lytic enzymes released from activated macrophages

treatment for ACD

steroids

pathology of ACD

mononuclear cell infiltration

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