Flashcards in Respiratory Immunology Hypersensitivity Deck (54)
Gel and Coomb's classification
Type I: immediate hypersensitivity (allergy)
Type II: direct cell killing (antibody mediated)
Type III: Immune Complex mediated
Type IV: Delayed hypersensitivity
IgE mediated antibody response to external antigen (allergen).
sign of an allergic reaction
skin rash with raised, red itchy bumps that may burn or sting
sign of an allergic reaction
rapid swelling of dermis, subcutaneous tissue, mucosa, and submucosal tissues. Very similar to urticarial, but urticarial occurs in the upper dermis, and angioedema in the dermis
angioedema is self-limiting, non-pitting oedema, not itchy unless associated with urticaria
which T cell is involved mainly in the allergic response? Which cytokines does it produce?
They produce IL-4, IL-5, IL-10 (anti-inflammatory), and IL-13
These instruct activated B cells to use epsilon heavy chains to secrete IgE
what are some examples of adverse reactions that are NOT allergies?
Ones that are not IgE mediated!
coeliac disease, lactose intolerance, bacterial food poisoning caffeine, irritable bowel syndrome, eating disorders
clinical features of Type I allergic disease
-occurs quickly after exposure to allergen (minutes to 1/2 hours)
-responses are stereotyped
-may be associated with more than one organ system
-urticarial, angioedema, asthma, allergic rhinitis and conjunctivitis, anaphylaxis
role of B lymphocytes, T lymphocytes and mast cells in allergic disease?
B lymphocytes: recognise antigen, produce antigen-specific IgE
T lymphocytes: help B lymphocytes to make IgE
Mast cells: inflammatory cells that release vasoactive substances
role of mast cells in allergic reactions?
-express receptors for Fc region of IgE
-on encounter with allergen, B cells produce antigen-specific IgE
-allergen is cleared
-residual IgE binds to circulating mast cells via Fc receptors
-upon SECONDARY exposure: allergen binds to IgE coated mast cells and disrupts cell membrane
-release of vasoactive mediators (histamine, tryptase)
-increased cytokines and leukotriene transcription
Intrinsic asthma is IgE mediated. True/ False?
Intrinsic asthma is "non-allergic" asthma - so it is NOT IgE mediated.
EXTRINSIC asthma is IgE mediated and is allergic disease
What happens clinically when an allergic reaction occurs in the lung? (First: release of histamine and other inflammatory mediators...)
-muscle spasm (causes bronchoconstriction, this manifests as a wheeze)
-mucosal inflammation (causes mucosal oedema and increases secretions, manifests as sputum production)
-inflammatory cell infiltrate (infiltration of lymphocytes and eosinophils into bronchioles - making sputum yellow. Infiltration is associated with chronicity).
apart from being mediated by IgE, what else can cause mast cell degranulation?
-drugs: morphine, opiates, aspirin and non-steroidal anti-inflammatories
-physical urticarial (urticarial in response to heat/ pressure)
This affects 20% asthmatics
wheeze 0.5-3 hours after ingestion
Non-steroidal anti-inflammatories (NSAIDs)
this is a drug class that groups together drugs that provide analgesia (pain-killing) and antipyretic effects, and, in higher doses, anti-inflammatory effects
This is aspirin-exacerbated respiratory disease, which is a condition consisting of:
-recurrent sinus disease with nasal polyps
-sensitivity to aspirin and other NSAIDs
Samter's triad may require diet modification
What is the investigation that can be done to find evidence of mast cell degranulation during anaphylactic episode?
measure the serum mast cell tryptase levels (tryptase is a marker for mast cell activation as its levels only rise in anaphylaxis, and not in local reactions)
skin prick test
a few drops of purified allergen are gently pricked onto the skin
a positive response is a local wheal and flare response
(Drugs can influence the response! The person should discontinue anti-histamines at least 48 hours before test)
This test is cheap, quick
BUT: requires experience for interpretation, and may (rarely) induce anaphylaxis
What's a specific IgE test (RAST test - radioallergosorbent test)
amount of IgE in serum against a specific allergen is measured
Sensitivity of this test is about 70% compared to skin prick test
How useful is measuring total IgE when investigating allergic disease?
-not useful in the diagnosis / investigation usually
-other things (vasculitis, lymphoma, drugs) can cause elevated IgE
-also, significant allergic disease can occur in absence of elevated IgE
management of type I hypersensitivity?
-block mast cell activation
-prevent effects of mast cell activation
-management of anaphylaxis
what can be used to block mast cell activation?
-sodium cromoglicate (mast cell stabiliser)
-It has poor oral absorption, can be used as a topical spray when allergen exposure is predicted
what can prevent the effects of mast cell activation?
-These are H1 receptor antagonists and are the main treatment of allergic disease
They block bronchoconstriction, bronchial smooth muscle contraction, vasodilation, and block the promotion of visceral hypersensitivity involved in itch perception
ALSO: leukotriene receptor antagonists
These block effects of leukotrienes which are synthesised by mast cells after activation. e.g, montelukast
They block the early and late phase
what anti-inflammatory agents can be used to treat allergic disease?
They inhibit formation of many different inflammatory mediators
what does an epi-pen do and what's it for?
it's a self-injectable adrenaline syringe, to use in anaphylaxis
It acts on B2 receptors to constrict arterial smooth muscle- increasing BP and therefore limiting vascular leakage, dilating bronchial smooth muscle- and so decreasing airflow obstruction
what is immunotherapy?
In a controlled manner: exposing more and more of the allergen the patient to train their immune system to not overreact. This induces regulator T cells (which produce IL-0 - an anti-inflammatory cytokine).
Type II hypersensitivity
Direct cell killing
Antibody binds to cell-surface antigen, resulting in activation of complement (leading to cell lysis/ opsonisation), and opsonisation (leading to antibody-mediated phagocytosis)
IgG and IgM are important here: they are good at activating complement - their conformational change allows them to activate C1
What happened if elimination of self-reactive B cells is not working, and a type II response is initiated?
Complement will be activated, and there is no pathogen: so tissue damage will occur
Which components of complement are known as "anaphylotoxins"?
C3a and C5a fragments
They are released after activation, and increase permeability of blood vessels - increasing traffic of cells to sites of infections
(They can also act indirectly to induce the same effects by activating mast cells (resulting in mast cell degranulation and release of histamine, tryptase, leukotrienes, and other pro-inflammatory mediators)
In type II hypersensitivity, how is there regulation of the process of complement activation?
Fragments of complement can dissolve the immune complexes which triggered them: switching off the process of complement activation