Intrinsic antigen
Normal antigen from self protein
Extrinsic antigen
Could mean foreign OR haptenized/modified self antigen
Mechanisms of antibody-dependent cytotoxicity in Type II Hypersensitivity
- 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
List of some common Type II Hypersensitivity disorders
- autoimmune hemolytic anemia
- autoimmune thrombocytopenia
- autoimmune neutropenia
- Goodpasture syndrome
Goodpasture syndrome
Type II hypersensitivty reaction against glomerular or alveolar collagen
Coomb’s test
- Purify erythrocytes from blood
- Add Coomb’s reagent (anti-human IgG or IgM)
- Observe for agglutination (clumping) due to cross-linking
Indirect Coomb’s test
- Purify patient plasma with patient antibodies
- Use standardized blood sample from donor
- Mix these two, then wait and add Coomb’s reagent
- 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
Desmosome vs Hemidesmosome
Extracellular desmosome proteins
Extracellular hemidesmosome proteins
Pemphigus foliaceus diagram
Pemphigus foliaceus
- 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
Pemphigus foliaceus on H and E
Pemphigus foliaceus patient
Pemphigus vulgaris diagram
Pemphigus vulgaris
- 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
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.
Acantholysis
The loss of intercellular connections of usually interconnected cells
Pemphigus vulgaris patient
Bullous pemphigoid diagram
Bullous pemphigoid H and E
Bullous pemphigoid patient
Skin diseases with a positive Nikolsky’s sign
Pemphigus foliaceus
Pemphigus vulgaris
Staphylococcal Scalded Skin Syndrome
Steven-Johnson Syndrome