Type III & IV Hypersensitivity (21)

In Type III, where do soluble antigens and antibody complexes form?

In tissues (localized) or in circulation (systemic)

Where can soluble antigen and antibody complexes of Type III get deposited if in circulation?

Renal glomerulus, dermal arterioles, joints, and small blood vessels in other sites

Most common site of deposition for Type III soluble antigen and antibody complexes formed in circulation

Renal glomerulus

In Type III, what does formation of immune complexes lead to?

Complement Activation (C5a and C3a)

In Type III, what changes does complement activation cause?

Vasodilation, mast cell activation, edema, and recruitment of neutrophils

In Type III, what problem can result due to changes caused by complement activation?

Inflammation and tissue damage

What causes localized type III hypersensitivity?

Antibody excess - high concentration of antigen-specific IgG at re-exposure

Localized type III hypersensitivity of the skin

Subcutaneous allergen immunotherapy and vaccination

Localized type III hypersensitivity of the lung

Hypersensitivity pneumonitis

Localized type III hypersensitivity of the eye

Uveitis

Systemic Type III circulating immune complexes leads to

Persistent antigen exposure (chronic infections and autoimmune) and delayed clearance of immune complexes

What does location of Type III determine?

Clinical signs

What aspects of location of Type III determine clinical signs?

Size of immune complexes, charge and glycosylation, blood flow, and predilection sites

Sequelae to Streptococcus equi infection

Purpura hemorrhagica

Clinical signs of Purpura hemorrhagica

Subcutaneous edema and mucosal hemorrhages

What can Purpura hemorrhagica lead to?

Thrombosis and infarcts in multiple organs

Purpura hemorrhagica treatment

Corticosteroids

What is Type IV mediated by?

CD4 Th1 cells

What does CD4 Th1 cells and IFN-gamma lead to?

Macrophage activation

What else can be involved in Type IV?

CD8 T cells

What are formed with tuberculosis?

Granulomas

What can cause false positives in tuberculin tests?

Other mycobacteria, Nocardia

What can cause false negatives with tuberculin tests?

Later or early stage of infection and decreased immune response

What are examples of haptens that cause contact allergy dermatitis?

Urushiol (poison ivy), antibiotics, metals, and insecticides

Mediates contact allergy dermatitis

CD4 and CD8 T cells (Th1 response)

Toxic epidermal necrolysis is almost always what?

Drug-associated

In toxic epidermal necrolysis, what do metabolites of the drug attach to?

Keratinocytes

Occurs after metabolites of the drug attach to keratinocytes in toxic epidermal necrolysis

CD8 T cells develop to modified antigens and kill the keratinocytes

Results of toxic epidermal necrolysis

Severe systemic signs, widespread painful skin and mucosal lesions, epidermis detaches, and infection of skin leading to sepsis

What is the milder form of toxic epidermal necrolysis?

Erythema multiforme