L14 Hypersensitivity and Allergy Flashcards
define type 1 hypersensitivity
exposure to an allergen (antigen) produces an IgE response. Mast cells bind IgE via their FceRI Fc receptor.
what happens when IgE binds to the allergen?
IgE crosslinking on mast cells, mast cell degranulation, release of mediators, brings about immediate hypersensitivity
examples of type 1 hypersensitivity
allergic rhinitis (hayfever) affecting 10% of population, eczema (atopic dermatitis), asthma, food allergies, diffuse urticaria (hives)
eczema (atopic dermatitis), define, immune cells involved
type I hypersensitivity reaction, immune cell infiltration under skin.
cytokine response is largely Th2, produces IL-4 and TNFα
name a drug which dampens the T cell response
corticosteroids which will inhibit cytokine synthesis
causes of urticaria (hives)
environmental, foods, medicines
what happens when an IgE is exposed to a parasite the second time?
triggers mast cell degranulation onto the surface of intestinal parasites
what cell produces IgE and what triggers its release
B cells and plasma cells make IgE in response to an antigenic stimulus
what does the presence of IL-4 and IL-13 indicate regarding class-switching of immunoglobulins?
they will trigger class switching from other isotypes to IgE
List properties of antigens
mainly proteins, water soluble, low Mw, Glycosylated, diverse functions, triggering immediate hypersensitivity
examples of allergens
dust mite (antigens in feces), cats (dander particles)
describe the wheal and flare reaction
inject allergen intradermally. wheal and flare will indicate IgE response if patient has been exposed to allergen previously.
name the MHC/HLA’s associated with allergy
DR2/Dw2, DR3/Dw3
if one of the two monozygotic twins has allergies, what is the likelihood the other twin also has it?
Approximately 50%
what percentage of Ig serum levels is typical of IgE?
0.001% of total serum Ig
Are levels of IgE elevated or decreased in allergies?
Elevated
name cell(s) and their receptor which binds IgE
basophils and mast cells bind IgE via their Fc receptors
name the different types of mast cells? (hint: think location)
connective tissue and mucosal (asthma) mast cells
name an instance where mucosal mast cells (MMCs) infiltrate the nasal epithelium.
hay fever patients during pollen season, bronchoalveolar fluid from lungs in asthmatics
what is the half life for IgE normally and what is its half-life when bound to mast cells?
normally 2 days, with mast cell bound is approx. 10 days.
what does the IgE-antigen complex crosslink with and what effect does this have?
cross links with the FceRI molecules on the mast cells. induces the release of mediators responsible for hypersensitivity reaction
percentage of asthma associated with IgE-mediated reaction and other non-immune stimuli of asthma
70% IgE related, other causes include drugs, cold, exercise.
name mediators in the immune system which elicit bronchoconstriction upon inhalation of allergens?
histamine, leukotrienes and prostaglandins including LTD4, are spasmogens which cause bronchoconstriction.
what effect do the spasmogens (histamine, LTD4, etc) have besides bronchconstriction?
induce edema, increase mucus secretion, smooth muscle constriction
name mediators released after asthma patient inhales an allergen that cause effects other than bronchoconstriction and give their function
IL-5 and TNFalpha are chemotactic factors which recruit cells like eosinophils, neutrophils, lymphocytes, and macrophages from circulation.
what impact does the inflammatory infiltrate have on the lung?
The inflammatory infiltrate chronically modifies the lung. effects include goblet cell hyperplasia (increased mucus), collagen deposition below the BM, and some evidence of possible smooth muscle hyperplasia.
what can be seen in exhalation of a patient with chronically modified lungs due to asthma?
increased exhalation of nitric oxide.
histopathological features of bronchial asthma
excess mucus, smooth muscle cell hypertrophy, submucosal inflammatory infiltration (lymphocytes and eosinophils), thickened BM.
what is meant by a biphasic response regarding bronchial asthma?
initial response (immediate), later response (hours later, flat-type response, potentially more dangerous)
effect of sodium cromoglycate on mast cells?
prevents mast cell degranulation and release of mediators like histamine, prostaglandins and leukotrienes. also blocks arachidonic acid
ventolin inhalers (active ingredient, what does it treat)
active ingredient is salbutamol, treats bronchospasm (sudden contriction of bronchiole smooth muscle)
beta2 agonists and asthma target and effect
binds beta2 receptors, blocks binding of epinephrine and norepinephrine. causes muscle relaxation and airway opening
describe desensitization as a treatment for hypersensitivity type 1
regular injections of allergen extracts. progressively increase dose. small 20 aa peptides approx.
risk of anaphylactic shock, should result in gradual change from IgE production to IgG
which T helper cell response is stronger in allergy sufferers? which interleukin does this produce?
Th2 cell response which produces IL-4
IL-4 promotes the production of which immunoglobulin?
IgE
are Treg cells pro or anti-inflammatory?
anti
what are some anti-inflammatory cytokines?
IL-10 and TGF-Beta
name the monoclonal antibody used to treat moderate-severe asthma and chronic hives, give mechanism
omalizumab, subcutaneous (once every 2-4 weeks), prevents IgE interaction with mast cells and its FceRI Receptor. removes ‘free IgE’
role of IL-4
amplifies IgE and histmamine induced vascular endothelium dysfunction, vasodilation, and anaphylaxis.
monoclonal antibody that targets IL-4, mechanism and what it treats
dupilumab, blocks IL-4 receptor which IL-13 also binds to. treats eczema, injections, can be used with topical steroids.
non-allergic food hypersensitivity example
lactose - milk - tolerance
define oral tolerance
oral tolerance is a state of local and systemic immune unresponsiveness that is induced by oral administration of ‘innocuous’ antigens such as food proteins.
name the 3 immune inductive sites in the GIT
Peyer’s patches, mesenteric lymph nodes and lamina propria
requirements of GALT
GALT must be able to:
- digest dietary antigens without causing untoward immune reactions
- protect the organism from pathogens.
explain T and B cell anergy and give a cause of it
this is where the T&B cells have been subjected to clonal deletion and are unresponsive. caused by high doses of orally fed food antigens.
name a cell involved in the induction of T&B cell anergy
dendritic cells
what happens if T&B cell anergy is not maintained?
this can cause chronic GIT inflammation and hypersensitivity.
what regulates the gut oral tolerance to dietary antigens?
T regulatory cells and their immunosuppressive effects stimulated by the uptake, processing and presentation of antigens in mucosal inductive sites.
what is a way of decreasing the likelihood of childhood peanut allergy?
introducing peanuts early can decrease the frequency of the develpment of peanut allergy among children who are at high risk for developing the allergy.
Systemic Lupus Erythematosus: define
a prototypic immune complex mediated disease, chronic, remitting and relapsing multi-system autoimmune disease.
SLE clinical manifestations
predominantly women
rashes, arthritis, glomerulonephritis, thrombocytopenia, CNS involvement also seen
characteristic features of SLE
auto-antibodies, often anti-nuclear (anti-DNA) antibodies as well as anti-ribonuclear proteins and anti-histones.
how to diagnose SLE
serology for anti-double stranded DNA antibodies.
MHC associated with increased risk of SLE
HLA-DR2, HLA-DR3
