Type II Hypersensitivity. Flashcards
Define ‘hypersensitivity’.
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:
- allergic reactions
- some infxs
- autoimmune diseases
- transplant rejection
- dysregulated activation of the immune system (genetic or induced)
- chronic inflammatory diseases of unknown etiology
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).
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?
immune-complex disease
What are the 3 forms of immune-complex ratios?
- antigen excess
- equivalence
- antibody excess
During the ‘precipitin reaction’ what immune-complex ratio causes the most precipitate?
equivalence zone
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)
- 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
What are the principle APC in the epidermis?
Langerhans cells.
What T cells do Langerhans cells from the epidermis present contact antigens to in the lymph nodes?
- CD4+ T cells
- TH1 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
Type IV HRs are activated by what 3 things?
- allergy
- infection
- autoimmunity
