Hypersensitivities

Question 1

What is hypersensitivity?

What is required for it?

Briefly list the four types.

Answer 1

Abnormal immune response to non-pathogenic antigens.

Requires a pre-sensitized state

ACID

Anaphylactic or atopic (IgE-mediated) [Type 1]

Cytotoxic (Ab-mediated) [Type 2]

Immune complex [Type 3]

Delayed (T cell mediated) [Type 4]

Question 2

Type I Hypersensitivity

Answer 2

• Anaphylactic or **Allergic **or **Atopic **or Asthma
• Immediate
• Sensitization or First exposure:
  
  • B cells/DCs encounters allergen and presents it to Th2 cells → Th2 cells release IL-4 → IL-4 promotes B cell differentiation into IgE-producing plasma and memory B cells → IgE binds Fc-episilon-receptor on mast cells/basophils → sensitized mast cells/basophils
  • Host experiences no symptoms from this rxn
• Second exposure to allergen:
  
  • Free antigen cross-links IgE on presensitized mast cells/basophils → mast cell/basophil degranulation → release of vasoactive amines like histamine
  • Host experiences symptoms

Question 3

How do histamines cause symptoms of hypersensitivity?

Answer 3

• Vasodilation:
  
  • In CNS → headache, nausea, vomiting
  • In CV system → cardiac arrythmia, HypoTN, anaphylaxis
• Endothelial permeability:
  
  • In Skin → flushing and urticaria
  • In Resp. system → nasal obstruction, sneezing, & bronchoconstriction
• Mucus secretion → nasal obstruction, sneezing, & bronchoconstriction in respiratory system

Question 4

Examples of T1H

Answer 4

• Bee sting
• Some food allergies
• Some drug allergies
• Allergic rhinitis (hay fever)
• Eczema
• Hives
• Asthma

Question 5

Type II Hypersensitivity

Answer 5

• Antibody-mediated cellular cytotoxicity
• IgM and IgG bind to fixed antigen on target cell → cellular destruction via:
  
  • Opsonization → phagocytosis
  • Opsonization → complement activation → complement-mediated lysis (MAC)
  • ADCC w/ NK cells → cell lysis & death

Question 6

Examples of T2H

Answer 6

• Autoimmune hemolytic anemia
• Pernicious anemia
• Idiopathic thrombycytopenic purpura (ITP)
• Erythroblastosis fetalis
• Acute hemolytic transfusion reactions
• Rheumatic fever
• Goodpasture syndrome
• Bullous pemphigoid
• Pemphigus vulgaris (also T4H)

Question 7

Type III Hypersensitivity

Answer 7

• Immune-complex deposition mediated inflammation
• Antibody-antigen complexes (IgG) activate complement → C3a and C5a anaphylaxatoxins → neutrophil recruitment and binding to mast cells/basophils → mast cell release of histamine and neutrophil release of lysosomal enzymes → vasodilation/platelet aggregation & tissue damage (respectively)
• **FYI **it is the small immune complexes that bind complement and cause problems. Large immune complexes are engulfed by phagocytes and cleared from the body.

Question 8

What are some sites of immune complex deposition?

Answer 8

• Glomerulus → glomerulonephritis
• Blood vessel walls → arteritis
• Synovial membranes → arthritis
• Skin → rash

Question 9

Examples of T3H

Answer 9

• SLE
• Polyarteritis nodosa
• Poststreptococcal glomerulonephritis
• Serum sickness (now caused by drugs acting as hapten, not serum)
• Arthus reaction (e.g., swelling & inflammation following the tetanus vaccine)

Question 10

Type 4 Hypersensitivity

Answer 10

• Delayed-type Hypersensitivity
• T-cell mediated
• sensitized T cells encounter antigen and then release lymphokines → macrophage activation
• No** antibody involved**

Question 11

Examples of Type IV Hypersensitivity

Answer 11

• Multiple sclerosis
• Guillain-Barre syndrome
• Graft-versus-Host diseae
• PPD test
• Contact dermatitis (e.g., poison IVy, nickel allergy)