Type II Hypersensitivity Reactions in the Skin

Question 1

Intrinsic antigen

Answer 1

Normal antigen from self protein

Question 2

Extrinsic antigen

Answer 2

Could mean foreign OR haptenized/modified self antigen

Question 3

Mechanisms of antibody-dependent cytotoxicity in Type II Hypersensitivity

Answer 3

• Antibody-mediated complement activation and MAC formation, followed by cell swelling and bursting
• Antibody-mediated complement activation followed by nonspecific neutrophil degranulation (here real damage is mediated by myeloperoxidase, proteinase 3, and peroxidase)
• Antibodies coating cell attach to C3b and are effectively opsonized and are able to be phagocytosed and destroyed, usually by splenic macrophages
• Antibody-dependent cell-mediated cytotoxicity (ADCC): NK cells recognize Fc region of IgG and degranulate to kill cell
• Non-cytotoxic effects (antibody-mediated cellular dysfunction): may result in Grave’s disease hyperthyroidism, mysathenia gravis, etc etc

Question 4

List of some common Type II Hypersensitivity disorders

Answer 4

• autoimmune hemolytic anemia
• autoimmune thrombocytopenia
• autoimmune neutropenia
• Goodpasture syndrome

Question 5

Goodpasture syndrome

Answer 5

Type II hypersensitivty reaction against glomerular or alveolar collagen

Question 6

Coomb’s test

Answer 6

1. Purify erythrocytes from blood
2. Add Coomb’s reagent (anti-human IgG or IgM)
3. Observe for agglutination (clumping) due to cross-linking

Question 7

Indirect Coomb’s test

Answer 7

1. Purify patient plasma with patient antibodies
2. Use standardized blood sample from donor
3. Mix these two, then wait and add Coomb’s reagent
4. Agglutination indicates anti-erythrocyte antibodies in patient serum

This test is not used to determine self-compatibility, but rather compatibility with exogenous blood samples prior to, for example, transfusion

Question 8

Answer 8

Question 9

Desmosome vs Hemidesmosome

Answer 9

Question 10

Extracellular desmosome proteins

Answer 10

Question 11

Extracellular hemidesmosome proteins

Answer 11

Question 12

Pemphigus foliaceus diagram

Answer 12

Question 13

Pemphigus foliaceus

Answer 13

• Type II hypersensitivity reaction against desmoglein-1
• Desmoglein-1 is more concentrated in the stratum corneum and stratum granulosum than in the lower layers, so this usually presents histologically as a superficial-level detachment of epidermis
• Because these are so superficial, they often erupt before they are ever observed, and so present clinically as erosions

Question 14

Answer 14

Pemphigus foliaceus on H and E

Question 15

Answer 15

Pemphigus foliaceus patient

Question 16

Pemphigus vulgaris diagram

Answer 16

Question 17

Pemphigus vulgaris

Answer 17

• Type II hypersensitivity reaction against desmoglein-3
• Since desmoglein-3 is found in lower levels of epidermis, like the basal layer, this presents histologically as a low-level epidermal detachment, with acatholysis of keratinocytes within the bulla
• Clinically presents as flacid blistering which eventually lyses and leaves behind crusting
• Mucous membrane involvement is an important clinical feature

Question 18

Answer 18

Pemphigus vulgaris H and E

Note that the detachment is not quite at the level of the basement membrane, since the hemidesmosomes are still intact. It is at once cell layer just above the basement membrane.

Question 19

Acantholysis

Answer 19

The loss of intercellular connections of usually interconnected cells

Question 20

Answer 20

Pemphigus vulgaris patient

Question 21

Bullous pemphigoid diagram

Answer 21

Question 22

Answer 22

Bullous pemphigoid H and E

Question 23

Answer 23

Bullous pemphigoid patient

Question 24

Skin diseases with a positive Nikolsky’s sign

Answer 24

Pemphigus foliaceus

Pemphigus vulgaris

Staphylococcal Scalded Skin Syndrome

Steven-Johnson Syndrome