L17- Allergies and hyper-sensitivities Flashcards
How do hypersensitivities hinder medical interventions?
People develop allergies to common drugs e.g. penicillin and some are allergic to egg proteins or preservatives in flu vaccines which gives vaccines bad press.
What is an example of a type I hyper-sensitivity?
Asthma- airway hypersensitivity. IgE-mediated. Get lung epithelium inflammation and smooth muscle contraction.
What are mast cells specialised in?
Mast cells specialise in releasing mediators of inflammation when the IgE/FcεR on their surface is cross-linked by allergen binding
What are Th2 cells specialized in?
Th2 cells specialise in making Interleukin-4 (IL-4) and helping B cells produce antibody of the type Immunoglobulin E (IgE)
What are the 3 steps of the first phase in a type-1 allergic reaction?
- Allergens stimulate type 2 helper T cells (Th2). Th2 cells make IL4 and help B cells make IgE type antibodies.
- B cells make IgE that recognize the allergen
- IgE circulates in blood and associates with Mast cells in tissues via FcεR
What is the first phase of a type 1 allergic reaction?
sensitisation: production of Ag-specific IgE
What is the second phase of a type 1 allergic reaction?
Re-Exposure and Activation of inflammatory response
What happens in phase 2 of a type-1 allergic reaction?
- the allergen binds to IgE on mast cells (in skin, airways, git)
- IgE signals to the mast cell to release its chemicals
- Results in vascular permeability, inflammation etc.
What does the release of the mast cells’ chemicals result in?
Results in vascular permeability, inflammation, muscle contraction, immune cell recruitment, swelling, redness, blistering, itching
What does a resting mast cell contain?
Granules containing histamine and other inflammatory mediators
What happens in an activated mast cell?
Multivalent antigen cross-links bind IgE antibody, causing release of granule contents.
What effects do mast-cell activation and granule release have on the GIT, airways and blood vessels?
GIT- increased fluid secretion, increased peristalsis (dia + vom)
Airways- decreased diameter, increased mucus (coughing, phlegm)
Blood vessels- increased blood flow, increased permeability (increase cells flowing)
Type 2 hyper-sensitivities?
IgG-mediated
Mounted against cell-associated antigens
Give an example of type 2 hypersensitivities
Foetal haemolytic syndrome
Describe type 3 hypersensitivities?
IgG-mediated
Mounted against soluble antigens in immune complex
Give an example of a type 3 hypersensitivity
serum sickness
Describe type 4 hypersensitivity?
Delayed type (DTH)
Contact hypersensitivity: allergic reaction following skin contact with allergen.
Cell-mediated (24-72h)
Swelling, redness, blistering, itching
Give an example of a type 4 hypersensitivity?
Poison Ivy
what does type 2 hypersensitivity involve?
Involves production of IgG or IgM that react with antigens on cells or tissue
What are 3 major syndromes of type 2 hypersensitivity?
- blood transfusion reactions
- haemolytic disease of the newborn
- drug-induced hypersensitivity
What happens in blood transfusion reactions?
If get wrong blood type, make IgM which binds to transfused RBC.
IgM good at fixing complement i.e. complement activated.
Causes fever, nausea, vomiting
What is haemolytic disease of the newborn?
When the mother is Rhesus negative but baby is Rh+
So mother makes rhesus specific B cells after first sensitisation event (usually birth)
How can haemolytic disease of the newborn be prevented?
By giving mother antibodies against Rh Ag before birth
What is type 3 hypersensitivity caused by?
Immune complexes of antigen and antibody
systemic disease: e.g. infection, local disease e.g. repeated inhalation of antigen, e.g. pingeon fancier’s disease
What is serum sickness?
Animal serum stimulates strong antibody response. If receive 2nd dose of serum, antibodies bind to the serum proteins forming immune complexes which are depositied in blood vessels. This causes fever, rash, arthritis and kidney disorder
What antibody does Type 4 involve?
Does not involve antibody. Involves Th, Tc and macrophages.
Is type 4 always against harmless antigens?
Not always. Can contribute to protection from pathogens.
one type is contact hypersensitivity e.g. poison ivy, nickel, hapten responses
What are the 4 types mediated by?
- IgE/Mast cell-mediated
- IgG-mediated
- IgG-mediated
- Cell-mediated
Compare all the hyper-sensitivities?
Type I – IgE / Mast cell-mediated
Type II – IgG-mediated, antigen expressed on a target cell. Eg. haemolytic disease of the newborn, Ag=Rh)
Type III – IgG-mediated, target is soluble antigen, caused by formation of immune-complexes & localised inflammation (eg infection (malaria, strep) or i.v. antigen/drug IgG kidney/liver damage)
Type IV – cell-mediated, localised, aka Delayed-type hypersensitivity (DTH) eg. contact dermatitis
How do you test allergies?
Skin prick test
ELISA- to measure antigen specific IgE levels in blood to common allergens
Please describe skin prick test
Put little bit of allergen in the epidermis, if they are sensitive they will have a wheal and flare rxn within minutes.
When you do an ELISA, what does presence of IgE in serum mean?
=Atopy- out of place.
The individual is said to be atopic.= predisposed to allergy (may not have clinical symptoms)
How do you treat allergy?
Treat the symptoms:
- anti-histamines, steroid anti-inflammatory drugs, adrenaline (epi-pen)
- low dose allergen therapies (de-sensitisation, raise IgG rather than IgE)
- oral tolerance: leads to T cell toleranc, retrain immune system to be tolerant of allergens.
What is concordance?
Incidence of disease in related individuals provides evidence of genetic/environmental basis of disease
Describe what concordance shows?
- 100% concordance (both get disease) in identical twins= purely genetic effect
- non-identical twins= indicates genetic effect.
Why do people get allergies?
Partly genetics overall rate of atopy= 15% Increases to 30%,50% with 1 or 2 parents. Concordance=60% in identical twins THEREFORE environment also plays a role
Which genes are involved in allergies?
Many genes involved:
Include MHC genes e.g. HLA-DR% is associated with birch pollen.
Non-MHC genes for immune response (e.g. IL4, FCεRI), Epithelial barrier function, tissue integrity
What are some ideas to explain why allergies/asthma have risen so much in the last 50 years?
Increased Th2 polarising substances/pollutants
Urbanization- cities, central heating, carpeting
Hygeine- elimination of parasites, vaccines, antibiotics
What is important for resistance to parasitic worm infection?
Th2 immunity
What kind of immunity is useful against parasitic worm infections? And which aren’t?
Th1-type immunity and cellular immunity (killer t cells) are not effective against parasitic worms.
Th2 and IgE-associated responses are effective at eliminating parasites.
(allergic IgE responses evolved to protect us against parasite infection)
What is the evidence for the hygiene hypothesis?
More allergies where there are fewer parasite infections and other infections.
Following de-worming, children get more allergies.
HOWEVER more allergies in SA than spain. INfluenza A virus infection linked to more asthma.
How are th1/th2 balanced to control allergy?
Th1 cells inhibit Th2 cells.
Th2 cells inhibit Th1 cells.
When inbalanced and too much th2-> more allergies-> causes hyper-sensitivity
What do th1 and th2 cells do?
th1 directly exterminate microorganisms.
th2 causes inflammation,kills parasites and neutralises microorganisms.
