Type II Hypersensitivity.

Question 1

Define ‘hypersensitivity’.

Answer 1

Immune-mediated tissue injury including allergic reactions and several other types of immune reactions that cause tissue damage either acutely or chronically.

Question 2

List 6 causes of hypersensitivity:

Answer 2

1. allergic reactions
2. some infxs
3. autoimmune diseases
4. transplant rejection
5. dysregulated activation of the immune system (genetic or induced)
6. chronic inflammatory diseases of unknown etiology

Question 3

List Gell and Coombs classifications of hypersensitivity reactions (I-IV)

Answer 3

I: IgE-mediated

II: mediated by Abs binding Ags on cell membrane, BM or components of the ECM

III: immune complex disease (soluble Ab-Ag complexes precipitate in tissues and cause acute inflammatory disease)

IV: delayed-type hypersensitivity and other cell-mediated reactions (mediated by T cells, doesn’t require Ab).

Question 4

List examples of Type II hypersensitivity reactions/diseases and the antigens involved:

Answer 4

• Autoimmune hemolytic anemia (Rh group, I antigen)–> anemia
• Autoimmune thrombocytopenic purpura (platelet integrin, GpIIb:IIIa)–> bleeding
• Goodpasture’s syndrome (noncollagenous domain of BM collagen type IV)–>glomerulonephritis, pulmonary hemorrhage
• Pemphigus vulgaris (epidermal cadherin)–> blistering of skin
• Acute rheumatic fever (streptococcal cell-wall antigens, Abs cross-react with cardiac m.)–> arthritis, myocarditis, late scarring of heart valves

Question 5

What is Type III hypersensitivity reaction also known as?

Answer 5

immune-complex disease

Question 6

What are the 3 forms of immune-complex ratios?

Answer 6

• antigen excess
• equivalence
• antibody excess

Question 7

During the ‘precipitin reaction’ what immune-complex ratio causes the most precipitate?

Answer 7

equivalence zone

Question 8

During the ‘precipitin reaction’ what immune-complex ratio is most likely with immune complex disease?

Answer 8

slight antigen excess

Question 9

List examples of immune complex disease:

Answer 9

• serum sickness (rxn to animal serum)
• hypersensitivity vasculitis (ex. drug rxn)
• Systemic lupus erythematosus (anti-DNA antibodies)
• persistent infection (ex. viral hepatitis)
• inhalation of mould, plant or animal antigens (ex. Farmer’s lung)

Question 10

What mediated Type IV hypersensitivity (cell mediated) reactions?

Answer 10

T cells (not Abs)

Question 11

What hypersensitivity reaction type is often a matter of ‘collateral damage’?

Answer 11

Type IV (cell-mediated)

Question 12

List examples of Type IV (cell-mediated) hypersensitivity reactions:

Answer 12

• delayed-type hypersensitivity (24-48 hr peak) Ag: proteins like insect venom, mycobacterial proteins : tuberculin, lepromin–> local skin swelling: erythema, induration, cellular infiltrate, dermatitis
• contact hypersensitivity; Ag: haptens: pentadecacatechol (poison ivy) DNFB, small metal ions: nickel, chromate–> local epidermal rxn: erythema, cellular infiltrate, vesicles, intraepidermal abscesses
• gluten-sensitive eneropathy (celiac disease); Ag: Gliadin –> villous atrophy in small bowel, malabsorption

Question 13

What type of effector T cells are involved in Type IV hypersensitivity?

Answer 13

Th1, Th2, Th17, CTLs

Question 14

List the adverse effects of persistent inflammation:

Answer 14

• overproduction of TGF-beta, cytokines, GFs
• fibrosis of tissue, loss of normal cells, impaired funx
• carcinogenic effect (ex. inc’d colon cancer in ulcerative colitis)

Question 15

TGF-beta, a powerful immunosuppressive cytokine, has lots of negative consequences when over-produced during chronic inflammation, like:

Answer 15

• fibrosis: pulmonary fibrosis, cirrhosis of the liver
• cancer cells over produce TGF-beta which helps them to protect themselves against anti-cancer immunity (promotes tumour metastesis)

Question 16

List the functions of TGF-beta:

Answer 16

• angiogenesis (via VEGF)
• leukocyte chemotaxis
• fibrosis (via AngII, CTGF)
• inhibits: B cells, CTL, NK, Th1, Th2, Mac/DC
• activated Treg (Foxp3+ cells) via IL2
• activated Th17 (via IL6)
• early inhibition of tumour cells, invasion/mets in late tumour cells
• activates/inhibits apoptosis

Question 17

What are the principle APC in the epidermis?

Answer 17

Langerhans cells.

Question 18

What T cells do Langerhans cells from the epidermis present contact antigens to in the lymph nodes?

Answer 18

• CD4+ T cells

- TH1 cells

Question 19

Bacterial superantigens can cause lethal systemic inflammatory disease via what?

Answer 19

Polyclonal T cell activation

ex. toxic shock syndrome (cytokine storm w TNF-alpha, IL2, IFN-gamma)

Question 20

Give an example of an inherited autoinflammatory syndrome (not initiated by T cells or Abs):

Answer 20

Familial Mediterranean fever (FMF), mutation in pyrin gene–> excessive production of IL-1.

clinically: sudden inflammatory attacks: peritonitis, pericarditis, arthritis

Question 21

List the 3 antibody mediated hyersensitivity reaction types:

List the one non-antibody hypersensitivity reaction type:

Answer 21

I (IgE-mediated), II (cytotoxic Ab), III (immune complex disease)

IV- cell mediated (T cell)

Question 22

List two causes dysregulation of the immune system:

Answer 22

• exposure to superantigens (polyclonal T cell actovation)

- hereditary autoinflammatory diseases (ex. FMF: IL-1 excess)

Question 23

Which of the following HR is usually organ specific versus systemic (multi-organ):

Type II (cytotoxic Ab)
Type III (immune complex)

Answer 23

Organ specific: Type II

Systemic: Type III

Question 24

Type IV HRs are activated by what 3 things?

Answer 24

• allergy
• infection
• autoimmunity