Allergy Immunotherapy Flashcards
What is an allergy?
Allergy is an exaggerated response from body’s immune system to an antigen.
What different types of hypersensitivity reactions are there?
- Type 1 (actual allergy)
- Type 2
- Type 3
- Type 4
What type 1 hypersensitivity is characterised by?
- IgE mediated
- Hypersensitivity reactions (anaphylaxis, hay fever)
- Very rapid - within minutes
What type 2 hypersensitivity is characterised by?
- IgG or IgM mediated
- Antibodies flag cells to be engulfed by CD8 T cells
- e.g. graft rejection, autoimmune disorders like Hashimoto’s
What type 3 hypersensitivity is characterised by?
- Immune complex mediated
- Immune complexes lead to activation of complement and attraction of neutrophils
- e.g. RA and SLE
What is type 4 hypersensitivity is characterised by?
- Cell-mediated
- T cells and macrophages
- e.g. contact dermatitis
- Usually days after exposure to antigen
What 2 phases are there in allergic reaction (type 1 hypersensitivity)?
- Induction phase
- Elicitation phase
What are steps of induction phase?
- First exposure to antigen
- Processing of allergen by DCs
- Induction of Tfh, th2 and ILC2 cells
- Class switching of B cells to IgE
- Production of IgE by plasma cells
- IgE binds to receptors on mast cells
What are steps of elicitation phase?
- Repeated exposure to allergen
- Mast cells degranulation
- Production of vasoactive amines, lipid mediators, enzymes
- Effect on organs (plasma leakage, hypotension, bronchospasm)
What are rules for allergens?
- Nearly always proteins or chemicals bound to proteins
- Usually requires repeated exposure
- Small, stable, soluble - absorbed intact and disseminated widely
- often enzymes
Barrier function in allergy
- Poor barrier functions can increase possibility of allergic disease (e.g. skin)
- Patients with eczema are more likely to develop food allergens
- Filaggrin (structural protein crucial for skin barrier function) mutations allow easier access of allergens to DCs
T cell help in allergy
- Th2 and Tfh cells are important in allergy induction and antibody production
- IL-4, IL-13 and IL-5 environment
Mast cells
- Myeloid-derived tissue resident cells
- Important for inflammatory response not only allergy
- Highly granulated with preformed mediators
Mast cells granules
- Histamine - increases vascular permeability, stimulates smooth muscle cell contraction (pre-stored)
- Tryptase - tissue damage (pre-stored)
- PGD2 - vasodilation, bronchoconstriction (newly-synthesised)
- Leukotrienes - Bronchoconstriction, mucus secretion (newly-synthesised)
What are characteristics of anaphylaxis?
- Cardiorespiratory compromise
- Dropped blood pressure + increased vascular permeability
- Bronchoconstriction
- May include hives
- May include gastrointestinal symptoms (diarrhoea, vomiting)
- May include neurological symptoms
- Can be fatal
- Treated with adrenaline
How is allergy diagnosed for IgE mediated allergy?
- Skin prick testing
- Intradermal testing
- Measuring serum specific IgE in the lab
First two if reaction after 15 min then diagnosed as allergy
How is T cell mediated hypersensitivity (type 4) diagnosed?
- Patch testing - read after 2 days
What immunotherapies are there for allergy?
- Repeated injections of high doses of allergen to induce tolerogenic DCs
- Within weeks induction of Tregs
- Tregs produce IL-10
- Class switch to IgG1 or IgG4
What allergy is immunotherapy successful for?
- Wasp venom - very effective
- Bees venom - very effective
- Grass pollen - quite effective
- Peanut allergy - slightly effective but only when done in kids
Food allergy
- Most commonly for eggs, meal, nuts and shellfish
- Very frequent
What is a cross-reactivity?
Some people have allergies for multiple things because of cross-reactivity for example plants evolved and some share similar proteins and same epitopes are shared and then a person will have allergic reaction to these shared epitopes on similar proteins.
Why some people have allergy for example only to raw apples but not baked apples?
Because proteins have different stabilities and can be broken down by:
- chemicals e.g. amylase in saliva
- heat e.g. cooking
- storage, pickling
