Type II Hypersensitivity

Question 1

“big picture” about type II

Answer 1

Abs against cell and tissue Ags cause tissue injury in T(II)HS rxn

Abs specific for tissue Ags may deposit in tissues and cause injury by inducing local inflammation

Question 2

Ab situation: who is target, what targets them

Answer 2

IgM, IgG targets tissue antigens on cell surfaces or extracellular matrixes

Question 3

T(II)HS: how it works from Ab to immune cell activation

Answer 3

IgG binds to neutrophil receptor and macrophage Fc receptor, activates leukocytes.

IgG/IgM activates CLASSICAL complement system— leukocyte recruitment and and inflammation

ROS and lysosomal enzymes damage adjacent tissues

Question 4

How it works: classical activation

Answer 4

1. Ab + Ag —> Ab-Ag
2. C1q + Ab-Ag —> C1qAbAg
3. C1qAbAg + Cr + Cs –C1qCrCsAbAg (Cqrs-Ab-Ag)
4. C1qrs/C4—> C1qrs + C4b + C4a
5. C4b binds to cell; C2 binds C4
6. Cs/C2 –> C2a + C2b
7. C(4/2)ba = C3 convertase
   etc—> MAC insertion, perforin action, cell lysis + C3a+C5a causing chemotaxis and leukocyte recruitment

Question 5

How it works: Fc mediated activation

Answer 5

IgG binds to neutrophils/macs Fc receptors, activates leukocytes —> inflammation

Question 6

Effector mechanism of Fc mediated activation (3 effector pathways)

Answer 6

1. Abs opsonize cell, activate complement, recruited phagocyte Fc receptor + C3b –> phagocytosis
2. Abs recuit leukocytes via direct binding to their Fc receptors OR through complement byproduct (C3a and C5a) binding to leukocytes
3. Hormone receptors may actually bind the Abs in the absence of hormones and overstimulate them (Grave’s disease)

OR

Abs may bind to neurotransmitter receptors and inhibit their activity (AcO inhibition: Myasthenia gravis inhibition) TSH inhibition

Question 7

Diseases of T(II)HS: hemolysis, anemia

Answer 7

autoimmune, hemolytic anemia

Erythrocyte membrane proteins are targeted (Rh blood groups)

Question 8

Diseases of T(II)HS: bleeding

Answer 8

Autoimmune (idiopathic) thrombocytopenic purpora

target is platelet membrane protein (integrins)

Question 9

Diseases of T(II)HS: nephritis, lung hemorrhage

Answer 9

Goodpasture’s syndrome

non-collagenous protein in basement membranes of kidney glomeruli and lung alveoli

Question 10

Diseases of T(II)HS: hyperthyroidism

Answer 10

thyroid stimulating hormone (TSH) receptor

Question 11

Diseases of T(II)HS: muscle weakness, paralysis

Answer 11

Myasthenia Gravis

acetycholine receptors targeted

Question 12

Diseases of T(II)HS: skin bullae (vesicles)

Answer 12

Pemphigus vulgaris

proteins in intracellular junctions of epidermal cells
epidermal cadherin

Question 13

Diseases of T(II)HS: myocarditis arthritis

Answer 13

Streptococcal cell wall inflammation, antibody cross-reacts with myocardial antigen