1.1.1 Type II Hypersensitivity Reactions Flashcards
What is the most common primary immunodeficiency?
Di George Syndrome
Deletion of part of chromosome 22q11.2
What is the main cause of immunodeficiency in the UK?
Malnutrition
What effects can the immune system have on the body in an autoimmune reaction?
Organ specific
Non-organ specific
What are some examples of organ specific autoimmune diseases?
Goodpasture’s syndrome
Haemolytic anaemia
Myasthenia gravis
Grave’s disease
What are some examples of non-organ specific disease?
Systemic lupus erythematosus
Rheumatoid arthritis
Define hypersensitivity
Antigen specific immune responses that are either inappropriate or excessive and result in harm to the host
What are the types of triggers for hypersensitivity reactions?
Exogenous antigens
Intrinsic antigens
Give 3 examples of exogenous antigens causing hypersensitivity reactions
- Non-infectious substances (innocuous, allergens)
- Infectious microbes
- Drugs (e.g. penicillin)
Give 2 examples of intrinsic antigens causing hypersensitivity reactions
- Infectious microbes (mimicry)
- Self antigens (auto-immunity)
What are the 4 types of hypersensitivity reactions?
- Type I- or immediate Allergy, environmental non-infectious antigens
- Type II- or antibody mediated
- Type III- or immune Complexes mediated
- Type IV- or cell mediated (Delayed), environmental infectious agents and self antigens
What antibody drives Type I reactions?
IgE mediated (Allergy)
What antibody drives type II and III reactions and how are they different?
IgG and IgM
Type II- antibodies against tissue bound antigens
Type III- antibodies against soluble antigens
What antibody drives type IV reactions?
Not antibody driven, cell mediated therefore T cells and macrophages mostly
What are the two phases of hypersensitivity reactions?
Sensitisation phase - First encounter with antigen, activation of APCs and memory effector cells
Clinically silent phase, asymptomatic
Effector phase -Pathologic reaction upon re-exposure to same antigen and activation of memory cells
Features of Type II hypersensitivity
- Develops 5-12 hours after re-encounter with infection
- Involves IgG (chronic infection) or IgM (acute infection) antibodies
- Targets cell bound antigens
- Induces different outcomes
What are the targets of type II hypersensitivity?
Exogenous
-Blood group antigens
-Rhesus D antigens
Endogenous
-Self antigens
What are the different induced outcomes of type II hypersensitivity reactions?
Tissue / cell damage
Physiological change in function
What immune mechanisms are involved in type II hypersensitivity reactions causing tissue/ cell damage?
Complement activation
-Cell lysis
-Neutrophil recruitment/ activation (C3a/ C5a)
-Opsonisation (C3b)
Antibody-dependent cell cytotoxicity
-NK cells- part of innate immunity
How do natural killer cells work?
NK cells have receptors for IgG, NK cell binds and releases its granules
What are two clinical examples of type II hypersensitivity reactions causing tissue damage? -complement activation
- Haemolytic disease of the newborn, -Rhesus D antigen
- Transfusion reactions, ABO system (mainly due to human error)
What are three clinical examples of type II hypersensitivity reactions causing tissue damage? -Antibody-dependent cell cytotoxicity
- Autoimmune haemolytic anaemia, RBC
- Immune thrombocytopenic purpura, Platelet
- Goodpasture’s syndrome, collagen in the basement membrane of the lung and glomerulus of the kidney
Give an example of a hypersensitivity type II reaction driven by IgM
Haemolytic transfusion reaction (ATR)
-Medical emergency (carry out ABC approach)
-Caused mainly by human error e.g. mislabled specimen
What is the immune mechanism behind haemolytic transfusion reaction?
- Incompatibility in the ABO antigens on RBCs
- Donor RBC lysis induced by type II hypersensitivity involving recipients IGM
What is the clinical outcome of haemolytic transfusion reaction?
Shock
Respiratory distress
Kidney failure
Death
What blood type can donate to all other blood types and what blood type is the universal plasma donor?
O- for whole blood
AB- for plasma
What is the pathophysiology of haemolytic disease of the newborn?
- Rhesus positive father
- Rhesus negative mother carrying rhesus positive foetus
- During delivery rhesus positive antigens from foetus enter maternal circulation
- Mother then produces anti-Rh +ve antibodies
- If the woman becomes pregnant with another Rh +ve foetus, anti-Rh antibodies will cross the placenta and destroy foetal RBCs
First encounter no effects as sensitisation occurs only affects the second baby
Anti-Rh antibodies cross the placenta as they are IgG
What complications arise as a result of haemolytic disease of the newborn?
- Hydrops fetalis- (fluid accumulation) liver failure, resulting in reduced albumin production, fluid moves into interstitium
- Liver/splenomegaly
- Severe hyperbilirubinaemia
- Kernicterus- brain damage due to bilirubin accumulation in brain
What is given to prevent anti-Rh antibodies forming, preventing the sensitisation phase?
RhoGAM
Rh0(D) immune globulin
- Give within 72 hours of giving birth
- 0.1% of mothers are not protected- too much blood enters maternal circulation?
How can we treat high antibody titres with Rh positive foetus?
Treat with plasmapheresis- removal of plasma which is replaced removing the anti-Rh antibodies
High dose of IV immunoglobulin
Intrauterine transfusions to ensure adequate blood supply to foetus through umbilical vein (not artery don’t make that mistake again)
How can haemolytic disease of newborn be diagnosed before birth?
-Check mother and fathers Rh antigens
-Check if mother and father had a child previously
- Indirect Coombs Test-antiglobulin test, used to check for anti-Rh antibodies
-Doppler scan of foetus to check for anaemia
-Foetal blood sample from umbilical vein for bilirubin
What physiological changes are caused by type II hypersensitivity reactions?
- Receptor stimulation,eg Graves disease, TSH receptor is the antigen that the antibody binds to
- Receptor blockade,eg Myasthenia gravis antigen is AChR
- Protein blockade, eg Pernicious anaemia, antigen is intrinsic factor in gastric parietal cells
What are the therapeutic approaches of type II hypersensitivity reactions?
Tissue/cell damage:
-Corticosteroids - anti-inflammatory
-Plasmapheresis - remove circulating antibodies and inflammatory mediators
-Splenectomy - removal of opsonised material
-IV immunoglobulin - blocks Fc receptor
Physiological change:
-Correct metabolism - antithyroid drugs in Graves
-Replacement therapy eg Pyridostigmine (Ach esterase inhibitor) in Myasthenia gravis,Vit B12 (IM) in pernicious anaemia
