1.1 hypersensitivity reactions Flashcards
what is the definition of the term hypersensitivity?
the antigen- specific immune responses that are either inappropriate or excessive and result in harm to host
what are the common features of hypersensitivity reactions?
sensitisation phase
- first encounter with the antigen. activation of APCs and memory effector cells. A previously exposed individual to the antigen is said to be sensitised.
effector phase
- pathological reaction upon exposure to the same antigen and activation of the memory cells of the adaptive immunity.
what are types of hypersensitivity reactions?
type I - Allergy - IgE driven
type II - antiBody mediated - IgG, IgM
type III - Complexes mediated - IgG, IgM
type IV - Delayed - cell mediated
what is the key difference between type II and type III hypersensitivity reactions?
type II = against cell bound antigen
type III = against soluble antigen
however, both involve IgG and IgM
what are the features of a type II hypersensitivity reaction?
usually developed within 5-12 hrs
involves IgG or IgM antibodies
targets cell bound antigens
- exogenous: blood group antigens, rhesus D antigens
- endogenous: self antigens
induces different outcomes e.g tissue/cell
damage and physiological damage
what is the mechanism of type II hypersensitivity reactions?
complement activation
- cell lysis
- neutrophil recruitment (c3a/c5a)
- opsonisation (c3b)
antibody dependent cell cytotoxicity
- NK cells
what is the importance of the compliment pathway in type II hypersensitivity reactions?
- opsonisation
- inflammation
- lysis of pathogens
- promotion of T cell response
- enhance immunological memory
how can a difference in maternal and paternal rhesus gene cause haemolytic disease of the newborn?
Rh+ father and Rh- mother
mother gets pregnant
the first pregnancy, is the sensitising pregnancy. The baby will be Rh+ and its antigens can enter the mothers blood during delivery. In response, mother will have IgG go to IgM (IgG can’t cross placenta, IgM can)
in the second pregnancy (= effector pregnancy), IgG that is anti Rh can cross the placenta and damage foetal red blood cells = haemolytic disease of the newborn
what are the properties of a type III hypersensitivity reaction?
usually develop within 3-8hrs
involve immune complexes between IgG and IgM and antigens
target soluble antigens
- foreign (infections)
- endogenous (self antigens)
tissue damage caused by the deposition of immune complexes in host tissue
what affects immune complex pathogenesis in type III hypersensitivity reactions?
- immune complex size
- host response
- local tissue factos
what factors give a poor prognosis of rheumatoid arthritis?
- high titre of rheumatoid factor
- <30 yrs old
- female
- joint erosions
name two diseases caused by type III hypersensitivity reactions.
Rheumatoid arthritis
Lupus
what are the properties of a type IV hypersensitivity reaction.
develops within 24-72 hrs
involves lymphocytes and macrophages
different subtypes = clinical outcomes
what is the pathogenesis of type III hypersensitivity reactions?
sensitisation phase = host first encounters antigen, get TH1 cells
effector phase = TH1 cells activate macrophage. this macrophages will try clear injected microbe by releasing chemicals = cause local damage to tissues but also recruit more TH cells = cytotoxic cells.
what are the features of type IV hypersensitivity: ‘contact hypersensitivity’ reactions?
contact hypersensitivity
- 48-72 hrs post exposure
- epidermal reaction
- requires endogenous protein
examples
- nickel
- poison ivy
- organic chemicals
what are the features of type IV hypersensitivity: ‘granulomatous sensitivity’ reactions?
granulomatous hypersensitivity
- occurs 21-48 days post exposure
- tissue damage
examples
- TB
- leprosy
- schistosomiasis
- sarcoidosis
what diseases are caused by type IV hypersensitivity to endogenous antigens?
- diabetes mellitus
- hypothyroidism
- rheumatoid arthiritis
what are the main blood groups of the ABO blood system?
blood group A – has A antigens on the red blood cells and have anti-B antibodies in the plasma
blood group B – has B antigens and have anti-A antibodies in the plasma
blood group O – has no AB antigens and have both anti-A and anti-B antibodies in the plasma
blood group AB – has both A and B antigens and have NO antibodies in the plasma
what are the universal donor and recipient blood groups?
Since group O individuals lack any A or B antigens on their red cells, they are considered universal blood donors.
Group AB individuals are universal plasma donors, as they lack AB antibodies.
how will haemolytic disease of a newborn present?
with jaundice
Destruction of red blood cells causes elevation of bilirubin level in the bloodstream. After delivery of baby with Haemolytic Disease of the Newborn (HDN), bilirubin present in the neonate’s blood is no longer cleared via the placenta, leading to the accumulation of bilirubin in the baby’s bloodstream (called hyperbilirubinemia) and other tissues/fluids resulting in JAUNDICE.
what is the main consequence of raised bilirubin levels in a baby?
If levels continue to rise, bilirubin may enter the brain to cause kernicterus, a potentially fatal condition that leaves permanent neurological damage in the babies that survive.
Why does a mismatch of the ABO system rarely causes HDN?
The naturally occurring anti-A or anti-B antibodies are IgM and do not cross the placenta
