Hypersensitivities Type III and Type IV

immune complexes

what are type III hypersensitivity reactions mediated by?

sensitization and elicitation

Type III require what two normal steps?

classical complement cascade/inflammation in the walls of blood vessels and in tissues

what do immune complexes cause reaction wise?

vessels through which plasma is filtered at high pressure

where do immune complexes especially deposit?

widespread vasculitis involving skin kidney or joints

systemic reaction of type III hypersensitivity?

persistent infection antigen

microbial Ag

infected organs (eg kidney)

site of persistent infection

autoimmunity antigen

self-ag

kidney, joints, skin and arteries

site of autoimmunity

extrinsic antigen

environmental Ag

lung

site of extrinsic

efficiently removed by phagocytes

large, normal immune complexes are what ? (too large and too small are opposite)

smaller

in the presence of antigen excess, immune complexes are ________.

immune complex deposits in kidney to cause kidney failure occurring after streptococcal pharyngitis or skin infection

post-streptococcal glomerulonephritis is due to

serum sickness

Originally described after systemic administration of antivenins or antitoxins that had been raised in other animal species like horses

immune complex disease studied

serum sickness was considered the first what?

rashes, joint pain, nephritis, hematuria and proteinuria

what are some major symptoms of serum sickness?

systemic lupus erythematosus

vascular injury when complexes of the antibodies (anti-DNA) and self antigens (DNA) deposit in vessels in different organs. There is impaired blood flow in skin, joints and kidneys

vasculitis, arthritis and nephritis

immune complexes cause VAN:

serum sickness (VAN causing)

drugs or infused foreign proteins

post streptococcal glomerulonephritis

cell wall antigens form streptococci

systemic lupus erythematosus (VAN causing)

nuclear antigens or other antigens

type IV hypersensitivity disease

issue injury is caused most often by cytokines produced by effector CD4+ and/or CD8+ T cells

release of inflammatory mediators and direct killing of host cells

what two things occur with type IV hypersensitivity diseases?

macrophages and neutrophils

what is the actual tissue injury within type IV hypersensitivity disorders caused by?

delayed-type hypersensitivity (DTH)

so called because it occurs 24-48 hours after an individual previously exposed to a protein antigen is challenged with the antigen infiltration of T cells and monocytes home to site of antigen challenge

mycobacterial antigen PPD

DTH reaction by _______ _____ _____ in skin arise in 24-48 hours helps detection of past or active TB

urushiol

Delayed type hypersensitivity (DTH) reaction in skin after exposure to ________ a small, lipophilic molecule found in poison ivy, poison oak and poison sumac

hapten action

Urushiol penetrates skin, covalently binding and altering multiple proteins

Th1 cells and CTLs

Subsequent skin exposure to urushiol elicits a local DTH reaction:

3 weeks

symptoms of poison ivy usually 24-48 hours after contact and dermatitis will resolve within

induration and erythema

PPD (purified protein derivative ex. mycobacterial PPD)

type IV hypersensitivity

nickel-induced contact hypersensitivity