Apr4 M1-Drug Hypersensitivities

Question 1

(EXAM) type 1 HS reaction cause and example

Answer 1

drug-specific IgE mast cell or basophil activation. mast cell degranulates and releases vasoactive substances
*ex: anaphylaxis

Question 2

(EXAM) type 2 HS reaction cause and example

Answer 2

Ab-dependent cell mediated cytotoxicity (ADCC). IgG or IgM bind surface of own cells (failure of immune tolerance OR self cell cross reacts with foreign Ag) or extrinsic Ag, causing the cells to be killed by ops, complement, NK cells
*ex: hemolytic anemia due to penicillin binding RBCs surface (Abs bind penicillin)

Question 3

(EXAM) type 3 HS and example

Answer 3

immune complex deposition mediated by IgM and IgG (and Ag #&raquo_space; Ab #), Ag to a drug. immune complexes form and deposit on blood vessel walls causing inflammation (1. neutrophil influx 2. MAC lysis 3. aggregation of plts 4. massive inflam)
*ex: serum sickness (vasculitis type of rx)

Question 4

(EXAM) type 4 HS and example

Answer 4

T-cell mediated (no Ab involved so not like type 1,2,3 HS) delayed response. CD4 TH1 + macrophage + infiltration of diff cell types after that: eosinophil infiltration and B cells involved too, mast cell degranulation too
*ex: contact dermatitis (IVb)

Question 5

5 types of type IV HS rx

Answer 5

IVa: CD4 th1 IFN-g. macrophages maculopapular rash
IVb: CD4 th2 eotaxin + eosinophil infiltration. maculopapular rash + bullous exanthemas (like contact dermatitis)
IVc: CD8+ T, perforin, granzyme B, kill keratinocytes. maculopapular rash + bullous + pustular
IVd: T cell (IL8) + PMN recruitment (neutrophils). pustular exanthema
IVe: CD8>CD4. other inflam cells. histamine-releasing factors cause mast cell degranulation. late urticaria (1-48 hrs later)

Question 6

2 signals of danger needed for a drug hypersensitivity rx to occur

Answer 6

1. presence of drug-derived epitope sensed by TCRs and Abs
2. constituents of damaged cells (damaged from drug, infection, trauma) acting as costimulatory signals (CK, creatine kinase for ex)

Question 7

when do you have the greatest chance of making someone have a rash (iatrogenic)

Answer 7

• give Abx to someone with viral infection
• you’re giving a 1. drug in someone with 2. IFN-g and preactivated T cells and immune system
• have all the factors needed for HDR*

Question 8

4 stages of HDR

Answer 8

1. drug Ag formation
2. Ag processing
3. Ag presentation to cognate cells
4. T and B cell responses

Question 9

hapten def

Answer 9

foreign molecules that trigger immune response only when attached to self proteins like large carrier soluble proteins, cell surface protein or MHC molecule

Question 10

dichotomous response in HDR

Answer 10

1. CD4 T cells respond to exogenous drug Ag-MHC2 complex

2. CD8 T cells respond to endogenous drug Ag-MHC1 complex

Question 11

(EXAM) different seets of T cells stimulated in HDR

Answer 11

• cytotoxic T cells (CD8, CD4)
• cytokine secreting T cells (CD4 th2 for B cell and IgE rx, CD4 th1 for cell mediated, B cell and non IgE rx. this second one is what gives maculopapular rashes and contact dermatitis via macrophages)
• T reg cells blocking T-cell priming