Lecture 30: Type IV Hypersensitivity

What is mediates type IV hypersensitivity reactions?

T cells

What types of T cells are involved in type IV hypersensitivity?

CD$+ and CD8+

What is not important in type IV hypersensitivity?

antibodies

True or false: type IV hypersensitivity is delayed.

true

The mechanism of type IV hypersensitivity reactions is established for elimination of _________.

intracellular pathogens

What is the mechanism of a type IV hypersensitivity reaction in response to soluble antigen?

APC presents tissue antigen to a CD4+ T cell, T cell releases pro inflammatory cytokines, tissue is injured

What is the mechanism of a type IV hypersensitivity reaction in response to a cell-associated antigen?

CD8+ T cells are activated to kill host cells causing cell death and tissue injury

What is the clinical presentation of type IV reactions?

induration: hard, raised lesions; erythema and vesicles

Give three clinical examples of type IV hypersensitivity.

1. Tuberculin reaction (mycobacterium spp. tuberculosis)

2. Contact dermatitis (poison ivy, nickel, flea collar)

3. Stevens Johnson Syndrome (drug coats cell and CD8+ destruction occurs)

Describe the type IV hypersensitivity pathway.

1. Antigen presented in tissue

2. Langerhans cells activated (engulf antigen and move to lymph)

3. APC meets with naive T cell → sensitized T cell or meets with memory T cell in lymph node

4. Lymphotactin recruits T cells and NK cells

5. IL-1, TNF-alpha, TNF-gamma, and chemokine secreted to activate basophils and macrophages

6. Basophils and macrophages secrete serotonin enzymes and oxygen metabolites to cause inflammation

What is used to identify individuals with TB?

mycobacterial extract

What is a type IV hypersensitivity endemic in cattle?

Bovine Tuberculosis

What are the four types of tuberculin tests used in cattle?

single intradermal, comparative, short thermal, stormont

What is the mechanism of allergic contact dermatitis?

1. reactive chemical on skin binds to PRRs (skin proteins like keratin can act as hapten carriers)

2. recognized by langerhans cells that present antigen to T cells in lymph node

3. Activated T cells produce IFN-y and IL-17 and activate cytotoxic T cells

4. after 24 hours to activate, T cells kill altered cells

What are the clinical signs of allergic contact dermatitis?

vesicles, itching, sloughing of skin

Re-exposure of allergens over time generates ______ reaction in allergic contact dermatitis.

stronger

What is the difference in pathogenesis of atopic dermatitis and allergic contact dermatitis?

atopic is type I hypersensitivity and allergic is type IV hypersensitivity

What area does allergic contact dermatitis usually target?

hairless areas

What is the pathological difference between atopic dermatitis and allergic contact dermatitis?

atopic involves mast cell and eosinophilic infiltration and edema and allergic involves mononuclear cell infiltration and gesticulation

What is Stevens-Johnson Syndrome?

a mucocutaneous reaction involving a T cell-mediated hypersensitivity to drugs

What are the clinical signs of Stevens-Johnson Syndrome?

rash that blisters into vesicles, shed large areas of epidermis and develop skin ulcers

What causes the skin ulcers of Stevens-Johnson Syndrome?

skin ulcers due to keratinocyte apoptosis, which is due to drugs or their metabolites binding to the epidermal cells and triggering CD95L expression, leading to triggering of destruction by CTLs and through apoptosis