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Flashcards in Type II Hypersensitivity. Deck (24):
1

Define 'hypersensitivity'.

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

2

List 6 causes of hypersensitivity:

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

3

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

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).

4

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

-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

5

What is Type III hypersensitivity reaction also known as?

immune-complex disease

6

What are the 3 forms of immune-complex ratios?

-antigen excess
-equivalence
-antibody excess

7

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

equivalence zone

8

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

slight antigen excess

9

List examples of immune complex disease:

- 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)

10

What mediated Type IV hypersensitivity (cell mediated) reactions?

T cells (not Abs)

11

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

Type IV (cell-mediated)

12

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

-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

13

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

Th1, Th2, Th17, CTLs

14

List the adverse effects of persistent inflammation:

-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)

15

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

-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)

16

List the functions of TGF-beta:

-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

17

What are the principle APC in the epidermis?

Langerhans cells.

18

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

-CD4+ T cells
-TH1 cells

19

Bacterial superantigens can cause lethal systemic inflammatory disease via what?

Polyclonal T cell activation

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

20

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

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

clinically: sudden inflammatory attacks: peritonitis, pericarditis, arthritis

21

List the 3 antibody mediated hyersensitivity reaction types:

List the one non-antibody hypersensitivity reaction type:

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

IV- cell mediated (T cell)

22

List two causes dysregulation of the immune system:

-exposure to superantigens (polyclonal T cell actovation)

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

23

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

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

Organ specific: Type II
Systemic: Type III

24

Type IV HRs are activated by what 3 things?

-allergy
-infection
-autoimmunity