Autoimmunity &Hypersensitivity Flashcards
What is hypersensitivity
An over reactive immune response causing pathology
What is the concentration of IgE in most peoples blood?
<60 IU/ml - very minute
What is the concentration of IgE in atopic peoples blood?
> 450 IU/ml - very high
- Still relatively low compared to other antibodies
What are mast cells derived from?
Basophil’s
What receptors do mast cells have? What do they do?
Fcε (epsilon) receptors - Bind to the Fc region of IgE antibodies.
How are mast cell activated?
Antigen binds and cross-links two IgE molecules on mast cells
Some drugs
C3a & C5a
What are three functions of mast cells granules?
- Chemoaattractants (neutrophils etc.)
- Activators - vasodilation, complement, platelet.
- Spasmogens - SM contraction and mucus secretion.
What are some common causes of allergies?
- Rhinitis (From breathing in)
- house dust mites
- animal dander
- pollen - Insect stings
- Proteins in venom
- Anaphylaxis is common (as in blood) - Food allergies
- Wheat, milk, peanuts - Small molecules (drugs)
- Penicillin, morphine
Common sites for allergies to occur
- Respiratory tract - rhinitis, sinusitis, asthma
- Skin - Urticaria
- Gut - food allergies
- Eyes - conjunctivitis
Allergy treatment
Avoidance - often difficult
Anti-histamines - for mild forms
Sodium cromoglycate - Stabilizes mast cells
Corticosteroids - for chronic atopy (asthma)
Sympathomimetics - Adrenaline (epi-pen)
Type 2 hypersensitivity
Antibodies against cell surface antigens (auto-immunity)
Result of type 2 hypersensitivity rxn:
ADCC
Complement activation
Frustrated phagocytosis
- when cell can’t be phagocytosed (blood vessel endothelial cells) so releases contents which damages cell.
Treatment given for Rh(D) negative mother who’s just given birth to Rh(D) positive baby.
Anti Rh antibodies to neutralize
Type III hypersensitivity:
Immune complex formed against free antigens.
When does type III rxn’s usually occur?
In chronic infections, when antibodies (IgM) are finally being produced by B cells but antigens are still present. Because they’re IgM, they form large immune complexes that lodge in small capillaries and activate complement/inflammation in them causing vasculitis and nephritis.
Blood vessel effects of immune complexes in type III rxn’s:
Microthrombus formation after deposition of immune complex
Complement activation causing neutrophil chemotaxis causing vascular damage (frustrated phagocytosis)
Type IV hypersensitivity reaction:
Mediated by CD4 T cells and takes about 24-48hrs.
What is a classic example of Type IV rxn? What is it?
Mantoux test: (Delayed-type hypersensitivity) Used to test immunity for pathogens
e.g Intra-dermal injection of protein pathogen. Some CD4 memory cells recognize antigen and release cytokines to recruit other immune response. This takes a day or two as CD4 has to find antigen, become activated and recruit cells to the site.
What is a hapten
Small molecules e.g. nickel which are conjugated with a protein. Usually nickel is to small to be recognized as an antigen but a hapten is.
What type of antibodies are natural autoantibodies.
IgM - common but low concentrationas
What anti bodies are found in elderly and SLE?
Anti-Nuclear antibodies
How rare are autoimmune antibodies
Rare - they form later in life meaning there is a change in the immune system somewhere during life.
Mechanisms of tolerance
Clonal deletion (central) during B and T cell ontogeny
Clonal regulation (peripheral) - If no co-stimulators present then anergy.
Clonal suppression - Treg control self reactivity
Ignorance - Where self reactive T cells and Ab’s antigens are hidden in immunologically privileged sites. e.g. ant. chamber of eye
What are some organ specific auto-immune conditions?
Myasthenia Gravis - Ab’s against ACh receptors
Pernicious anaemia - Ab’s against B12/IF .
Idiopathic thrombocytopenic prpura - Ab’s against platelets
What is a way auto-immunity can develop?
Molecular mimicry - Antibodies made against pathogens + HLA peptide from previous infections that happen to LOOK the same as self peptides and HLA receptors.
Don’t get it in all people with the same bacteria as HLA restrictions.
