Lecture 24: type IV hypersensitivities

immune mechanism of type IV hypersensitivity

-CD4 T cells
-CD8 CTLS

mechanism of injury: type IV hypersensitivity

-macrophage activation, cytokine inflammation
-cell lysis

type IVa hypersensitivity is mediated by

-IFN-gamma, TNF-alpha (Th1 cells)
-macrophage

EX: tuberculin reaction

type IVb hypersensitivity

Mediated by Th2 cells --> IL-5, IL-4, IL-13
-eosinophils
ex: chronic asthma, allergic rhinitis, exanthema

type IVc hypersensitivity

Mediated by cytotoxic T cells --> perforin, granzymes
-T cells
EX: contact dermatitis

type IVd hypersensitivity

-mediated by IL-8, GM-CSF
-neutrophils

EX: AGEP

type IV hypersensitivity is aka

T-cell mediated
delayed type

type IV hypersensitivity mechanisms of injury

-for a, b, and d: cytokines induce inflammation
-for c: directly killing target cells

name some antigens that cause TIVH response

-infectious agents (TB)
-environmental antigens/chemicals
-autoantigens
-transplanted organs

describe patch tesing

-used to diagnose type IV hypersensitivity

-used to diagnose suspected contact dermatitis

-apply thick panels of allergens to skin, check reactions after several days

list some TIVH diseases

rheumatoid arthritis, multiple sclerosis, type I DM, IBS, psoriasis
-transplant rejection

p-i reactions

-pharmacologic interaction with immune receptors
-drug binds to MHC or TCRand stimulates T cell

direct p-i reaction

drug binds to TCR

indirect p-i reaction

drug binds MHC-peptide

type IVa hypersensitivity is mediated by what cells?

-primarily Th-17 (IL-17) and Th1 cells
-IL-17 recruits neutrophils
-IFN-y activates macrophages' and TNF recruits leukocytes

types of IVa reactions

-tuberculin reaction: mantoux (PPD) test
-granuloma formation
-tuberculoid granuloma
-allergic contact dermatitis

what causes the induration of PPD skin tests?

-TH1 effector cel recognizes antigen and releases cytokines which act on vascular endothelium
-recruitment of macrophages mediates tissue damage

false positives of tuberculin skin tests often appear with

-previous infection to non-TB mycobacterium
-prior BCG vaccination
-incorrect administration or interpretation of test

false negatives of tuberculin skin tests result from

-very recent or very old TB infection
-very young age
-recent live virus vaccine
-some viral diseases

what causes granuloma formation

CMI removes most intracellular organisms
-continuous stimulation/accumulation of macrophages

what causes contact dermititis?

-haptens penetrate skin and trigger immune response
-langerhans cells present Ag to T cells
-keratinocytes secrete cytokines
-damage is rash is monocyte/cytokine mediated

list some common allergens that cause contact dermatitis

poison ivy most common
-nickel, gold
-laatex, rubber
-plant resins/saps
-formaldehyde
-bacitracin, neomycin
-cosmetics

what are the two phases of contact dermatitis/DTH?

-sensitization: keratinocytes activated by allergen; produce TNF, IL-1, GM-CSF
-challenge: subsequent exposure, rapid activation of Th1 cells; IFN-y causes macrophage infiltration

Type IVb reactions

-eosinophil activation, triggered by Th2 type immune response
-seen in chronic asthma airway remodeling

type IVd reactions

-neutrophilic inflammation mediated by T cells
-acutee generalized exanthematous pustulosus

Acute Generalized Exanthematous Pustulosis (AGEP)

type IVd disease

type IVc hypersensitivity is aka

delayed type hypersensitivity

mediation of type IVc hypersensitivity

-CD4 T cells recognize Ag on APC, become Th1 cells
-Th1 cells secrete IL-2 and IFN-y
-takes 24-48 hours

type IVc hypersensitivity is found in

contact dermatitis, drug reactions, hepatitis, graft rejections

Stevens-Johnson Syndrome

skin detachment of <10% of body

type IVc

-commonly cauased by meds

Toxic Epidermal Necrolysis

detachment of >30% of the body

Type IVc

-commonly caused by meds

IVc reactions cause what?

the cell death causes epidermis to separate from dermis (ex TEN and SJS)

which type has no cytokines involved

type IVc; uses cell death by cytotoxic T cells