Allergy and Transplantation Flashcards
What is an allergy?
Type 1 (immediate) hypersensitivity Excess immune response to allergens, harmless antigens
Allergies damaging clinical needs?
Key drugs e.g. penicillin make conditions harder to treat
Egg proteins in vaccines trigger egg allergies, adding to vaccine hesitancy
Type 1 hypersensitivity in asthma?
IgE in airways = lung epithelium inflammation, smooth muscle contraction and mucus production
- Sensitisation
Ag specific IgE produced: allergen stimulates Th2 = IL4 for B cell IgE production, which circulate and associate with mast cells in mucosal and connective tissues with Fc region - Re-exposure and activation
Allergen binds Fc IgE on mast cells, cross linking receptors
Mast cells release mediators of inflammation = symptoms
Role of mast cell localisation?
GI tract = increased fluid secretion and peristalsis = diarrhea, vomiting
Airways = decreased diameter, increased mucus = congestion, wheezing, swelling in nasal passages
Blood vessels = increased blood flow and permeability = greater fluid in tissues increasing lymph drainage to nodes = effector response
Anaphylaxis?
Systemic response triggered by excessive histamine - blood vessels severely dilate = unconsciousness, airways narrow, oedema occurs
Often in nut allergies
Other hyper sensitivities?
Type 2; IgG mediated against cell or cellular-matrix associated antigens
e.g. haemolytic anaemia
Type 3; IgG against soluble antigens in immune complexes
e.g. lupus
Type 4; delayed type responding to contact hypersensitivity i.e. allergic response from skin contact, cell mediated and only involves T cells
e.g. MS
Type II hyper sensitivities?
IgG/IgM
React with anitgens on cells/tissues
Cause blood transfusion reactions, haemolytic disease of the new born, haemolytic anaemia, drug induced hypersensitivity (autoimmune)
Blood transfusion - IgM binds RBCs for complement activation
Haemolytic disease of newborn - Rhesus antibodies interacting
Type III hypersensitivities?
Immune complexes causes this
Systemic disease e.g. infections like malaria
Local disease e.g. Farmer’s lung from mould in hay
e.g. serum sickness
Animal serum = antibodies
Re-injection = immune complexes
Type IV?
NO ANTIBODIES
Not always harmless antigens e.g. poison ivy response
Cell mediated and localised
Allergy testing?
Skin prick test giving wheal and flare reaction quickly, and late phase later on
ELISA - detects IgE in serum when it should not be suggests you are atopic i.e. predisposed to allergens
Patch tests for type 4 - left for 24-72 hours
Causes of allergy?
Again, twin studies show concordance suggesting genetic component, not 100% = environment too
Genetic causes of allergy?
MHC genes
Non-MHC genes e.g. for rest of immune response
Environmental causes of allergy?
Increased Th2 polarising substances e.g. pollutants
Urbanisation - more common in developed countries
Hygiene
Expososome increased
Hygiene Hypothesis?
Children from more rural environments less likely to develop allergy as exposed to more things early on helps immune system develop
Old Friends hypothesis?
Few worm infections in areas with common AD and allergy - suggests losing these from our microbiome contributes to disease
Role of parasitic worms?
Th2 and IgE evolved in tandem with worm infections, where IgE initial response was to protect us from these
Disproving the hygiene hypothesis?
Not universal - South/Latin America has higher asthma than Spain/Portugal
Worm infections still common in parts of USA
Asthma on the rise in poverty-living African Americans
Influenza A in childhood linked to increased asthma
Industrialised nations still dirty - pollution, food additives
Balanced immune systems?
Th2 cells inhibiting Th1 and vice versa
Skewing of this e.g. allergic Th2 responses more upregulated
Treating allergies
Avoid allergen
Anti-histamines
Steroids to reduce inflammation
Epi-pens
Types of allergen therapies?
Low dose - de-sensitisation, raising IgG rather than IgE
Antibody - blocks IL4 cytokines that promote Th2 activation of B cells
Oral tolerance - exposure to antigens that usually cause T cell tolerance with Tregs
Worm therapy - may induce Tregs, reduce Th2. Hookworms used clinically to treat asthma
What did Peter Medawar find about rejection?
First set rejection kinetics - rapid rejection of graft to allogeneic (different MHC) recipient
Second set rejection - even more accelerated, same donor to same recipient i.e. showing immunological memory
Transfer of 2nd set kinetics to naive mouse if T cells from a mouse who has received a transplant are transferred to naive, who then receives a graft from same donor as the first mouse
Immune suppressant drugs?
Another key breakthrough in transplantation science -e.g. Azathioprine and cyclosporin A
Current issues?
Managing organ rejection - drugs must be taken long term, but this also suppresses the immune system leading to infections etc
Organ supply - very limited
Ageing society
What affects frequency of transplantation?
Organ availability
Other treatments
Risk/reward
Clinical demand
