Type III and IV Hypersensitivity Reaction

Question 1

What is a type III hypersensitivity reaction?

Answer 1

Soluble antigen and specific antibody form a complex depositing in blood vessel membrane and causing tissue damage by inflammation (vasculitis)

Clinical: >3-6 hours after antigen exposure

Question 2

How is a type II reaction generated?

Answer 2

Antibody binds to an antigen as a soluble complex and deposits in small blood vessel.

C3b binds to exposed Fc site and complement activation/neutrophilic inflammation in vessel occurs

Question 3

What is serum sickness?

Answer 3

Type III reaction against foreign antigens (e.g. antivenom)

Question 4

How is vasculitis induced in a type III reaction?

Answer 4

Immune complex deposition leads to platelet aggregation and microthrombus formation

Immune complexes/complement products from activated cascade act on complement receptor on basophil/mast cell to allow for release of vasoactive amines

Question 5

How do you differentiate a “hive” from type I reactions and type III reactions?

Answer 5

Type I - presence of itching

Type III - presence of vessel damage indicates source is non-allergic

Question 6

What is Rheumatoid Arthritis?

Answer 6

Type III hypersensitivity reaction

Rheumatoid factor is patient’s autoantibody of IfM Fab component directed against Fc portion of own IgG

Question 7

What is the therapy for rheumatoid arthritis?

Answer 7

Anti-cytokine monoclonal antibody

Anti-B cell monoclonal antibody

Question 8

What is the antibody isotype of immune complex of Henoch Schonlein Purpura?

Answer 8

IgA

Question 9

What is post-streptococcal glomerulonephritis?

Answer 9

Type III hypersensitivity reaction

Causes immune complex deposition in the capillary/kidney unit (glomerulus)

Question 10

What is the arthus reaction?

Answer 10

Local immune complex deposition after antigen injection in skin with preformed antibody present

Occurs in presensitized individuals

Edema, necrosis, complement activation

Question 11

How can you test for type III hypersensitivity?

Answer 11

Skin or renal biopsy - leukocytoclastic vasculitis with infiltrate of neutrophils (lumpy bumpy appearance)

Hypocomplementemia - complement activation depletes C3/C4

Small vessel vasculitis in favored locations of kidney, joint, skin

Question 12

What is the therapy for type III hypersensitivity reactions?

Answer 12

Glucocorticoids and plasmapheresis (acute flare)

Immunosuppressants fro autoimmune disease

Question 13

What is a type IV hypersensitivity reaction?

Answer 13

Inflammation via CD4 T cell cytokine activation of macrophages and /or CD8 T cell mediated cell lysis

> 48 hours to weeks develop

Question 14

What is Steven’s Johnson Syndrome/Toxic Epidermal Necrolysis?

Answer 14

Type IV hypersensitivity reaction caused by drugs such as penicillin, sulfa or anti-seizure

Also caused by infection such as HSV or Mycoplasma

Question 15

What is the mechanism of SJS/TEN?

Answer 15

CD8 T cell response to drug hapten or antigen causes T cell activation which kills keratinocytes via cytolysis

Also induces apoptosis

Question 16

What is the therapy for SJS/TEN?

Answer 16

Cyclosporine, glucocorticoids

Question 17

What is the mechanism of Allergic Contact Dermatitis?

Answer 17

Antigens are soluble haptens which bind to keratinocytes enabling immunorecognition

Memory T cells (4 and 8) in dermis proliferate on 2nd exposure and inflammatory infiltrate ensues

Question 18

What is the therapy for allergic contact dermatitis?

Answer 18

Antigen removal and glucocorticosteroids

Question 19

How do you test for type IV hypersensitivity?

Answer 19

Sensitizing agent placed on skin and then examined in 48 hours

Question 20

What antigen properties enable type IV reaction?

Answer 20

Environmental chemical antigens

Hard to clear, chronic intracellular pathogens

Medication (haptens, e.g. penicillin and sulfa drugs)

Self antigens - MS, insulin dependent diabetes, RA

Question 21

What infection is a source of delayed type IV reaction?

Answer 21

TB

Question 22

What does the PPD (Mantoux test) reflect?

Answer 22

Reflects INF-gamma production by antigen specific CD4 T cells

Immunosuppression will decreasee the size of the reaction