Flashcards in Type II Hypersensitivity. Deck (24):
Immune-mediated tissue injury including allergic reactions and several other types of immune reactions that cause tissue damage either acutely or chronically.
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
List Gell and Coombs classifications of hypersensitivity reactions (I-IV)
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).
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
What is Type III hypersensitivity reaction also known as?
What are the 3 forms of immune-complex ratios?
During the 'precipitin reaction' what immune-complex ratio causes the most precipitate?
During the 'precipitin reaction' what immune-complex ratio is most likely with immune complex disease?
slight antigen excess
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)
What mediated Type IV hypersensitivity (cell mediated) reactions?
T cells (not Abs)
What hypersensitivity reaction type is often a matter of 'collateral damage'?
Type IV (cell-mediated)
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
What type of effector T cells are involved in Type IV hypersensitivity?
Th1, Th2, Th17, CTLs
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)
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)
List the functions of TGF-beta:
-angiogenesis (via VEGF)
-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
What are the principle APC in the epidermis?
What T cells do Langerhans cells from the epidermis present contact antigens to in the lymph nodes?
-CD4+ T cells
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)
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
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)
List two causes dysregulation of the immune system:
-exposure to superantigens (polyclonal T cell actovation)
-hereditary autoinflammatory diseases (ex. FMF: IL-1 excess)
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