Type IV Hypersensitivity (MT2)

Delayed type: Major cells

Th1 cells + macrophages (cause cell injury)

Delayed type: Major cytokine

Interferon gamma

Delayed type hypersensitivity (DTH)

Slow, reaction peaks around 24-48 hours after exposure to Ag (tend to be extracellular)

Can be non-granulomatous or granulomatous

Non-granulomatous etiologies

Contact dermatitis: red, dry, itchy rash

Tuberculin skin test: Raised bump from local Ag

DTH non-granulomatous pathogenesis

1. Ag exposure

2. APC activated + present MHCII

3. Th1 activation + proliferation

4. Th1 migrate to tissue and secrete interferon gamma → Supercharge macrophages

5. Inflammation from released macrophage enzymes

Ag eliminated → Inflammation ends

Ag persists → Granuloma formed

Non-granulomatous inflammation

Combination of aggregated active macrophages and the acute inflammation they are causing

Contact dermatitis

Skin inflammation due to Ag, dry itchy, red blistering rash

Etiologies: Preservatives (BAK in glaucoma drops), antibiotics (aminoglycosides), cosmetics (fake lash adhesives), urushiol (poison ivy)

Treatment: Topical steroids (short time because it can thin skin)

Purified Protein Derivative (PDD)/Tuberculin/Mantoux Test

Purified protein derivative from mycobacterium tuberculosis injected causing an induration (bump reaction in one spot) caused by activated macrophages

If exposed to M. tuberculosis → Elevated wheal within 24-72 hours

Order chest X-ray to rule out TB, can be treated with antibiotics to prevent disease

IGRA/spot test

Takes blood and exposes it to TB and look for IFN gamma

Granulomas

Walls off Ag to prevent damage to rest of body

Anoxic inside, kills obligate aerobes

Granuloma structure (inside → out)

Dead cells + Ag

Macrophages (can fuse to form multinucleated giant cells)

Th1 cells

Collagen

Fibroblasts

Most common granulomatous uveitides

Non-pathogenic: Sarcoid, chronic chalazion, foreign bodies

Pathogens: Syphilis, TB, toxoplasmosis, zoster, fungi

SSTTZ

Where can granulomas appear in the eye?

• Uveal tract - Typically indicates systemic condition

• Lid

• Conjunctiva

Sarcoidosis

Inflammatory disease of unknown etiology, characterized by non-caseating granulomatous inflammation

Chronic chalazion

Sterile granuloma around indigestible lipid

Meibomian gland occlusion causes lipid to harden

Treatment: Warm compress, treat early before collagen and fibroblasts (otherwise need surgery)

Hordeolum/Stye/Acute Chalazion

Bacterial infection with acute inflammation

Treatment: Warm compress and antibiotics

Clinical pearls for DTH

• Granuloma

• Onset - Immediate vs. 24-48 hours

• History

Understand etiology for treatment