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
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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