Hypersensitivity Intro Flashcards
Define hypersensitivity
The antigen specific immune responses that are either inappropriate or excesssive + result in harm to host
Types of triggers (antigens)
- exogenous: non infectious substances, infectious microbes, drugs
- intrinsic: infectious microbes, self antigens (autoimmunity)
Types of hypersensitivity reactions
- Type I or immediate (Allergy)
- Type II or antiBody-dependent cytotoxicity
- Type III or immune Complexes mediated
- Type IV or cell mediated (Delayed)
What is the sensitisation phase?
- first encounter with antigen
- activation of APCs + memory effector cells
What does it mean is a person is ‘sensitised’?
A previously exposed individual to the antigen is said to be ‘sensitised’
What is the effector phase of hypersensitivity reactions?
Pathologic reaction upon re-exposure to the same antigen + activation of memory cells of adaptive immunity
Describe type II hypersensitivity
- antibody dependent cytotoxicity
- usually develops within 5-12hrs re encounter
- IgG + IgM involved
-
targets cell bound antigens:
-exogenous: blood group antigens, Rhesus D antigens
-endogenous: self antigens (autoimmune) - induces tissue/cell damage or physiological change
Outline Type II hypersensitivity associated with tissue/cell damage
- IgG + IgM antibodies raised against cell bound antigens
- complement activation: cell lysis, neutrophil recruitment, opsonisation
- antibody dependent cell cytotoxicity: natural killer cells
What immunoglobulins are related to hypersensitivity reactions
Type I - IgE
Type II + III - IgG + IgM
Clinical examples of Type II hypersensitivity assocaited with tissue/cell damage - complement activation
What is the antigen?
- haemolytic disease of newborn - Rhesus D
- transfusion reactions - ABO system
When does Type II hypersensitivity occur?
Within 5-12 hours re-encounter
Clinical examples of Type II hypersensitivity assocaited with tissue/cell damage - antibody-dependent cell cytoxicity
What is the antigen?
- autoimmune haemolytic anaemia - RBCs
- immune thrombocytopenic purpua - platelets
- goodpasture’s syndrome - collagen in glomerular basement memebrnae
Outline haemolytic transfusion reaction
- incorrect blood is given
- incompatibility of ABO antigens on RBCs
- donor RBC lysis induced induced by type II hypersensitivity reaction IgM
- causing shock, respiratory distress, kidney failure + death
Outline Type II hypersensitivity associated with physiological changes
immune response against receptor
(Type V)
- IgG reaction against cell bound antigens
- receptor stimation
- receptor blockade
- protein blockage
Clinical examples of Type II hypersensitivity assocaited with physiological changes
What is the antigen?
- receptor stimulation: Grave’s disease - TSH receptor
- receptor blockade: myasthenia gravis - acetylcholine receptor
- protein blockade: pernicious anaemia - intrinsic factor
Treatment of type II hypersensitivity due to tissue/cell damage
- corticosteroids
- plasmapheresis
- splenectomy
- intravenous immunoglobulin > blocks Fc receptor
Treatment of type II hypersensitivity due to physiological change
- correct metabolism e.g. anti-thyroid drugs in Grave’s disease
- replacement therapy e.g. pyridostigmine in Myasthenia gravis or B12 in pernicious anaemia
Describe Type III hypersensitivity reactions
- develops within 3-8 hours
- involves immune complexes between IgG or IgM
- targets soluble antigens
- tissue damage caused by deposition of immune complexes in blood vessels
What are the key factors affecting immune complexes pathogenesis in Type III hypersensitivity?
What does this cause?
- Complex size
- Persistent of antigen
- Host response
- Local tissue factor
. - Persistence of ICs + deposition in blood vessels
Clinical examples of Type III hypersensitivity reactions
What antigen is involved?
- rheumatoid arthritis - Fc portion of IgG
- glomerulonephritis - infectious microbes
- systemic lupus erythematosus - double stranded DNA
When does Type III hypersensitivity occur?
3-8 hours
Describe Type IV hypersensitivity
- develops within 24-72 hours
- involves lymphocytes + macrophages
- triggered by environmental factors, infectious microbes + drugs
What are the subtypes of Type IV hypersensitivity
- contact hypersensitivity
- tuberculin hypersensitivity
- granulomatous hypersensitivity
Describe contact hypersensitivity
Subtype of Type IV hypersensitivity
- occurs 48-72 hours post exposure
- epidermal reaction
- e.g. nickel, poison ivy, latex, organic chemicals
Diagnosis of contact hypersensitivity
Patch testing
Outline granulomatous hypersensitivity
Subtype of Type IV hypersensitivity
- occurs 21-48 days post exposure
- tissue damage
e.g. TB, leprosy, schistosomiasis, sarcoidosis
Outline tuberculin hypersensitivity
Subtype of Type IV hypersensitivity
- occurs 48-72 hours post exposure
- dermal reaction
Therapeutic approaches to type III + IV hypersensitivity
- NSAIDs
- corticosteroids
- steroid sparing agents
- monoclonal antibodies
4 examples of organ specific harmful effects of immune system
- goodpasture’s syndrome
- myasthenia gravis
- haemolytic anaemia
- grave’s disease
2 examples of non-organ specific harmful effects of immune system
Systemic lupus erythematous
Rheumatoid arthritis
What are the main blood groups defined by ABO system + their associated antigens
A - A antigen
B - B antigen
AB - A+B antigen
O - none
Signs + symptoms of haemolytic disease of the newborn
- jaundice
- dark urine + pale faeces
- hepatosplenomegaly
- oedema
- kernicterus
Pathophysiology of haemolytic disease of the newborn
- Rhesus + father and Rhesus - mother > R+ fetus
- during 1st pregnancy, mother hasn’t been sensitised
- Rhesus antigens from fetus enters mother’s blood
- in response to fetal Rh antigen, mother produces anti-Rh antibodies
- if there is a second pregnancy with R+ fetus, her anti-Rh fetus damages fetal RBCs
Prevention of haemolytic disease of newborn
RhoGAM
Binds to fetal blood in mum’s circulation
Prevents mum from developing anti-Rh antibodies
Describe the direct Coombs test
- test baby’s blood
- does it have anti-D antibodies bound to baby’s blood?
Describe indirect Coomb’s test?
- Test mum’s blood
- Is mum producing anti-D antibodies?
When is RhoGam administered?
- if baby is Rb+: 30 weeks + at birth
- if unkown: 8 weeks
What is kernicterus?
Bilirubin induced neurological damage
Examples of type IV hypersensitivity reactions
- Hashimoto’s disease
- type I DM
- MS
- Sjogern syndrome
