S2 L1 Hypersensitivity Reactions and Diseases Flashcards
What is the main cause of immunodeficiency in the UK?
Malnutrition in the elderly
Give some examples of autoimmune conditions.
Disease or systemic specific
What is the definition of hypersensitivity?
- Antigen-specific immune responses that are either inappropriate or excessive and result in harm to host by damaging tissue or changing a tissues function
- Mechanisms are the same as the normal immune response
What are the two categories of triggers for hypersensitivity?
- Exogenous antigens:
- Non infectious substances (pollen, dust)
- Infectious microbes (sepsis)
- Drugs (penicillin)
- Intrinsic anigens:
- Infectious microbes (mimicry like rheumatic fever)
- Self antigens (auto-immunity)
What are the different types of hypersensitivity reactions?
- Type I / immediate (Allergy)
- Type II / antiBody mediated
- Type III / immune Complexes mediated
- Type IV / cell mediated (Delayed)
- First 3 are antibody mediated, but 4 has antibody but not primary cause
What are the two phases of hypersensitivity reactions?
Sensitisation:
- First encounter with antigen
- Activation of APCs and memory effector cells
- A previously exposed individual to the antigen is said to be “sensitized”
Effector:
- Reaction upon reexposure to the same antigen and activation of the memory cells of the adaptive immunity
Which antigens are involved in Type I hypersensitivity?
Environmental non-infectious antigens
How long does it take for a type II hypersensitivity reaction to be triggered, what antibodies are involved and what antigens are targeted?
- 5-12 hours
- IgG or IgM
- Causes tissue damage or physiological change
- Targets cell bound antigens so organ specific:
- Exogenous: blood group antigens, rhesus D antigens
- Endogenous: self antigens
What are the mechanisms in type II hypersensitivity that lead to cell/tissue damage?
- Complement activation: cell lysis (MC), neutrophil recruitment/activation (C3A/C5A), opsonisation (C3b)
- Antibody-dependent cell cytotoxicity: NK cells
- Antibody binds to antigen and activates complement
What are some examples of diseases caused by a type II hypersensitivity reaction?
What is the mechanism behind haemolytic transfusion reactions?
- Type II hypersensitivity IgM
- Incompatability in ABO or rhesus D antigens
- Donor RBC destroyed by recipients immune system through IgM
- Caues shock, kidney failure, circulatory collapse and death
What is the mechanism behind haemolytic disease of the newborn?
Type II hypersensitivity reaction IgG
- Involves Rhesus D antigen
- Mismatch between mother(Rh-) and child (Rh+) and thus antibodies are produced against Rh+ antigen
- After 2nd pregnancy, IgG antibodies cross placenta and cause HDN
How can we prevent haemolytic disease of the newborn?
When mother is Rh -ve she is given RhoGAM within 3 days of miscarriage or delivery of Rh +ve infant to bind all of the Rhesus antibodies
What mechanisms in a type II hypersensitivity reaction lead to physiological changes and give two examples of disease caused by this?
- Antibody can stimulate or block a receptor
What therapeutic approaches can be used to combat tissue/cell damage and physiological change induced by type II hypersensitivity reactions?
- Immune suppression for complement activation
- Plasmapheresis for circulating antibodies and inflammatory mediators
- Splenectomy for opsonisation/Phagocytosis
- Intravenous immunoglobulin (IVIG) for IgG degradation and hopefully bad IgG will degrade
(see image for physiological change)
What is plasmapheresis therapy and what diseases is it used for?
- Removal of antibodies from the plasma allowing short term relief and healing of damaged tissue
- Used in myasthenia gravis, goodpasture’s syndrome and grave’s as these all are primary antibodies that drive the disease
How long does it take for a type III hypersensitivity reaction to be triggered, what antibodies are involved and what are the target antigens?
- 3-8 hours
- Immune complexes between IgG or IgM and antigens
- Targets soluble antigens: foreign (infection) and endogenous (self-antigens)
- Tissue damage by deposition of immune complexes in host tissues
What are the 3 key factors in type III hypersensitivity pathogenesis?
Where do immune complexes mainly deposit in the body with a type III hypersensitivity reaction?
- MULTISYSTEMIC DISEASE unlike type II which is more organ specific
- Joints, kidney, small vessels, skin
What are some examples of diseases caused by type III hypersensitivity reactions?
- Rheumatoid arthritis (self-antigen)
- Glomerulonephritis (infectious)
- SLE
What is the pathophysiology of glomerulonephritis?
Type III hypersensitivity reaction following infection
- Bacterial endocarditis
- Hep B infection
What are the mechanisms involved in rheumatoid arthritis and what are some poor prognosis factors?
- Antigen: Anti-Rheumatoid factor Fc portion of IgG
- Articular and extraarticular features with episodes of inflammation and remission
What is the immune mechanism involved in type III hypersensitivity?
- Intermediate-sized IC’s deposited in tissue
- Complement activated
- Neutrophil chemotaxis, adherence then degranulation
What type of hypersensitivity reaction is SLE?
- Type III
- Antigen: Ds-DNA
- Most prevalent immune complex disease that is more common in females
How long does it take for type IV hypersensitivity to be triggered, which antibodies are involved and what are the different subtypes?
What are the mechanisms of tissue destruction in a type IV hypersensitivity reaction?
- APCs activate TH1 cells
- Granulomas
What is the duration of contact hypersensitivity and the reactions involved?
- 48-72 hrs post exposure
- Epidermal reaction and requires endogenous proteins but exogenous antigens
caused by things like nickel, poison ivy, organic chemicals
What are some examples of granulomatous hypersensitivity reactions?
- TB
- Leprosy
- Schistosomiasis
- Sarcoidosis
Occur 21 to 48 days post exposure and forms to try and contain microbe so occurs due to persistence of antigen
State the duration of tuberculin hypersensitivity and the reaction involved.
- 48-72hr
- Dermal reaction (induration and swelling)
- Type IV hypersensitivity
Whata are some diseases caused by Type IV hypersensitivity to endogenous antigens?
Both Hashimoto’s and Grave’s disease are hypersensitivity reactions that affect the thyroid, however they are different categories of reactions, what are they?
- Hashimotos: Type IV, treat with thyroxine
- Grave’s: Type II, treat with thyroidectomy
What are some anti-inflammatory drugs and monoclonal antibodies used in type III and IV hypersensitivity reactions?
What are some of the signs and symptoms of jaundice in a newborn?
- Yellow discolouration
- Muscle and abdominal pain
- Dark urine/pale stools
- Loss of appetite
- Fever
(hydrops fetalis is swelling in at least 2 compartments)
What is the Rhesus antigen and what is the issue if a father is Rhesus positive?
- If you have the Rhesus D antigen this means Rhesus +ve but if you have C,c, E,e you are negativ
- Father could make a fetus with Rhesus +ve blood which crosses the placenta. A rhesus -ve mother will then make Anti-D IgG that can cross the placent and attack the fetus RBCs causing HDN
What is the main complication of raised bilirubin levels in a newborn’s blood due to HDN?
Kernicterus = brain damage due to bilirubin accumulation in the brain
Occurs as the placenta is no longer clearing bilirubin so baby cannot conjugate all of the bilirubin itself
How can we diagnose HDN before a baby is born and how can we predict it without testing?
- Check mother and father to see what rhesus antigen they have and ask them if they have had a child before
- Indirect Coombs Test
- Doppler scan of fetus MCA to see if anaemia and if there is take a fetal blood sample
Why does a mismatch of ABO between mother and fetus rarely lead to HDN?
- The anti-A and anti-B antibodies in the plasma are IgM so cannot cross the placenta
What type of hypersensitivity reaction is HDN?
- Type II as IgG mediated against D antigen causing a loss of function
- The antibodies opsonise the red blood cells causing them to be destroyed by the liver and spleen
How can we treat a mismatch in rhesus antigens?
Give the mother RhoGAM to prevent her from making antibodies and becoming sensitised
Which blood types are universal blood donors and universal plasma donors?
- Universal blood donors: O
- Universal plasma donors: AB
What is the difference between the direct and indirect coombs test?
