Hypersensitivity Flashcards
4 signs of immunodeficiency
SPUR
Severe infection - life threatening
Persistent - even with antibiotics
Unusual - organism or location of infection
Recurrent
Causes of immunodeficiency
HIV Asplenic Malnutrition - main cause Diabetes Organ transplant
Hypersensitivity
Inappropriate or excessive antigen specific immune response that results in harm to the host
Types of hypersensitivity triggers
Exogenous:
- allergens e.g. pollen, dust
- infectious microbes - sepsis
- drugs - Steve -Johnson syndrome
Intrinsic:
- host antigens (autoimmune)
- infectious microbes - mimicry
Mimicry
The antigen of the pathogen has a similar structure to the host therefore the immune response attacks the pathogen and the host
E.g. rheumatic fever
Which triggers are harder to remove
Intrinsic antigens - therefore causes chronic inflammation as harder to eradicate
Type I hypersensitivity
Trigger: environmental, non infectious antigens
Mechanism: Immediate allergy response
Antibody: IgE
Type II hypersensitivity reaction
Trigger:
- exogenous - blood group antigens (transfusion), rhesus D antigens (HDN)
- endogenous - self antigens
Mechanism: antibody mediated immune response
Antibody: IgG or IgM
Target: membrane bound antigens in tissue and cell surfaces
Outcome:
- tissue or cell damage
- physiological change e.g Grave’s disease
Time: develops within 5 -12 hours
Type III hypersensitivity reaction
Trigger:
Exogenous- infection
Endogenous - self antigen
Mechanisms: immune complexes circulate in the blood and deposit in host tissue causing infection
Antibody: IgG and IgM
Target: soluble antigens
Time: 3-8hrs
Type IV hypersensitivity infection
Trigger: environmental infectious agents and self antigens
Mechanism: cell mediated delayed response
Antibody: are involved but predominantly lymphocytes and macrophages
Time: 1-3 days
Sensitisation phase of hypersensitivity
First encounter with the antigen
Activated antigen presenting cells and memory effector cells
Effector phase
Re-exposure to the same antigen
Causes a pathological reaction
Activates memory cells of the adaptive immune response
Type II hypersensitivity mechanism
- Antibody binds to antigens on the cell surface
- Activates the compliment cascade
- cell lysis by macrophages
- neutrophil activation and recruitment - C3a and C5a
- opsonisation - C3b - Also activate antibody dependent cell cytotoxicity by NK cells
Diseases caused by Type II hypersensitivity reactions
Autoimmune haemolytic anaemia
Immune thrombocytopenia purpura
Goodpasture’s syndrome - nephritic syndrome
Grave’s disease - hyperthyroidism as antibody stimulates the TSH receptor continuously
Myasthenia gravis - antibodies against acetylcholine receptors, impairs neuromuscular signalling causing paralysis and weakness
Difference between IgM and IgG
IgM antibodies are larger
Haemolytic transfusion reaction consequences
Life threatening
Can cause shock
Kidney failure
Immune mechanism of haemolytic transfusion reaction
Incompatibility in the ABO or rhesus D antigens
Therefore donor RBCs are destroyed by recipient’s immune response
Caused by IgM
Blood types and antibodies
A - anti B
B - anti A
AB - none
O - anti A and anti B
Rhesus +ve - no antibodies against rhesus D antigens
Rhesus -ve - antibodies against rhesus D antigens
Haemolytic disease of the newborn (HDN)
Father - rhesus positive
Mother - rhesus negative - has rhesus D antibodies
Child - rhesus positive - has Rhesus D antigens
- Some foetal RBCs cross the placenta and enter the maternal circulation in the third trimester of the first trimester. Therefore the mother becomes sensitised and produces IgG
- In subsequent pregnancies as already sensitised, IgG crosses tube placenta and binds to the foetal rhesus D antigens causing haemolytic disease of the newborn
How to treat haemolytic disease of the newborn
Give Rhogam to the mother to prevent sensitisation
Rhogam contains antibodies against rhesus D antigens therefore the mother does not need to create its own IgG and become sensitised
Treatment of type II hypersensitivity reactions
Anti- inflammatory drugs:
- prevent complement activation
- cytotoxic and can cause serious side effects
Plasmapheresis:
- separate platelets and haematocrit
- remove the inappropriate antibodies and inflammatory mediators
- introduce plasma back into the circulation with supportive fluid
Splenectomy - reduces opsonisation and phagocytosis
Intravenous immunoglobulin (IVIG) - igG degradation
Grave’s - Anti thyroid drugs or thyroidectomy
Myasthenia gravis - pyridostigmine - increases Ach in the neuromuscular junction
Key factors affecting type III hypersensitivity
Complex size:
- small and large immune complexes are cleared
- intermediate immune complexes are difficult to clear
Host response:
- low affinity antibody
- complement deficiency - can cause immune complex type III hypersensitivity disease as less immune complexes reach the liver to be degraded
Local tissue factor:
- haemodynamic factors
- physio chemical factors
Where do immune complexes deposit usually
Joints
Kidney
Small vessels - where birfucates
Skin
- multisystem disease
Immune complexes
Small IC - cleared by monocytes and macrophages
Large IC - cleared once opsonised
Intermediate IC
- deposits in tissues and activates the complement cascade
- causes neutrophil chemotaxis - C5a
- neutrophils adhere to the cell surface and degranulate releasing cytotoxic substances e.g ROS
