Allergy and asthma Flashcards
where do all immune cells come from?
hematopoietic stem cells
which cytokines act on naive CD4 T cells to turn them into T regulatory cells?
IL-2
TGF-beta
which cytokines act on naive CD4 T cells to turn them into Th1
IL-12
which cytokines act on naive CD4 T cells to turn them into Th2
IL-4
which cytokines act on naive CD4 T cells to turn them into Th17
TGF beta IL-6 IL-21 IL-23 IL-1beta
which cytokines are produced by T reg cells
TGF-beta IL-10 IL-35 STAT6 FOXP3
which cytokines are produced by Th1 cells?
IFN-gamma
LT alpha
STAT4
T-bet
Which cytokines are produced by Th2 cells?
IL-4 IL-5 IL-13 STAT6 GATA3
Which cytokines are produced by Th17 cells?
IL-17A IL-17F IL-22 IL-21 CCL20 STAT3 ROR gamma T
what do T reg cells do?
suppresses tumour immunity
promotes immune tolerance
maintains lymphocyte homeostasis
what do Th1 cells do?
promotes tumour immunity
intracellular pathogens
drives autoimmunity
what do Th2 cells do?
extracellular pathogens
allergy
asthma
produce IgE
what do Th17 cells do?
controversial tumour immunity
breaks immune tolerance
extracellular bacteria
autoimmunity
T cell balance
equal numbers of Th1 and 2 cells
inhibit each other
autoimmune diseases
more Th1 cells than Th2
atopy
more Th2 cells than Th1
T reg cells
maintain the balance between Th1 and 2 cell populations by realsing IL-10 and TGF-beta
what is IgE used for?
kills helminths and parasites by activation eosinophils
what happens in initial sensitisation?
allergen presented to DC cells which recognise them as foreign and so presents them on MHC 2 of DCs to naive T cells which makes them become Th2 cells which activates naive B cells that produce IgM and then they are class switched through DNA splicing so they produce IgE. Clonal expansion - memory cells
IgE receptor
FCepsilonRI receptor which allows IgE to bind to cells
where are IgE receptors?
mast cells - tissue
basophils - blood
B lymphocytes - lesser extend
what cytokines cause class switching?
IL-4 and 5
how do B cells class switch?
DNA splicing
re-exposure to allergen
allergen/ antigen binds to IgE, has to cross link - bind to 2 IgE molecules and causes degranulation of the mast cell
mast cell mediators
biogenic amines
lipid mediators
cytokines
enzymes
biogenic amines released by mast cell
histamines
lipid mediators released by mast cells
Prostaglandins - PGD2
leukotrienes - LTC4
cytokines released by mast cells
TNF alpha or beta
Enzymes released by mast cells
exogenous tryptase
what do histamines do?
vasodilation and vascular leak
what do lipid mediators do?
bronchoconstriction
intestinal hypermotility
what do cytokines do?
inflammation
what do enzymes do?
tissue damage
phases of allergy
immediate and late
late phase
recruit Th17 cells which produces IL-17 and IL-22 which causes activation of eosinophils and recruitment of basophils
what do eosinophils do?
release mediators, chemokines and proinflammatory cytokines
increased inflammatory cells migration and activation
what do basophils do?
have their own IgE molecules
how long does it take for inflammatory cells to be recruited?
6 hours after exposure
eosinophils
elevated/ recruited in lungs and blood of asthmatics
allergy and parasitic infections
what activates eosinophils?
activated by cytokines
what do eosinophils release?
release toxins, leukotrienes and cytokines
what do eosinophils cause?
activation causes bronchial hyperactivity - wheezing
smooth muscle cell activation and hyperactivity
can also be caused by IFN gamma and TNF from Th1 cells when they are recruited due to imbalanced immune system
What do Il-4,13 and CCL5 do?
cause increased endothelial-cell adhesion and inflammatory cell transmigration so even if allergen is removed inflammatory process will continue
why does an allergy cause eczema?
atopic dermatitis
Th1 cells produced IFN gamma, TNF and CD95L which induces keratinocyte apoptosis and release of chemokines and proinflammatory cytokines
chronic allergic reaction
persistent inflammation
prolonged or repetitive exposure to antigens
characterised by large numbers of innate and adaptive immune cells
substantial changes in the extracellular matrix and alterations in the number, phenotype and function of structural cells in the affected tissues
fibroblasts
implicated in normal healing process and scar formation
deposit extracellular matrix
cause thickening of basement membrane
fibroblasts in lungs
tryptase affects fibroblasts in lungs but this can cause increase in extracellular matrix and thickening of basement membrane, further narrowing the airways
what happens in severe chronic asthma?
vasodilation hyperplasia and mucus hypersecretion leukocyte infiltration eosinophilia hypertrophy of smooth muscle collagen deposition partial occlusion of bronchial lumen by mucus plug thickening of basement membrane oedema desquamation/ degradation of epithelium
what are the 2 types of asthma?
type 2 inflammation
non-type 2 inflammation
non type/ Th 2 inflammation
caused by smoking
irritants
pollutants
infections
what happens in non Th2 inflammation
similar reaction but call in Th1 cells quicker and recruit neutrophils
clinical presentations of allergy
anything presented via dendritic cell can be perceived as non self or pathogenic antigens
which can then trigger an IgE mediated reaction. This can be anything
causes of IgE mediated reactions?
drug hormones genetics systemic illness food allergies stress
common drugs that cause IgE mediated reaction?
antibiotics NSAIDs - second most common allergy biologicals contrast agents blood
what infections cause hives IgE mediated reaction?
infections - Hepatitis, EBV, herpes
chronic parasites
cutaneous fungal infections
what foods cause allergies/ IgE mediated reaction?
peanuts tree nuts milk eggs wheat soy fish shellfish sesame
IgE mediated symptoms
sneezing runny nose nasal congestion discomfort in mouth swelling of lipd itching hives reddening loss of consciousness lethargy blue-white lips/ nails itchy eyes redness of eyes swelling of eyelids raspy voice wheezing whistling sound when breezing coughing difficulty breathing abdominal pain nausea diarrhoea
hives
releasing of plasma into epidermis due to vascular leak
clinical presentation of asthma
shortness of breath - exercise and interval
expiratory wheeze
cough, especially nocturnal
episodic
reversible
diagnosis based on likelihood and assessment
when making an asthma diagnosis
rationale for the diagnosis needs to be documentation
differential diagnoses in asthma
hyperventilation in teenagers viral induced wheeze primary ciliary dyskinesia bronchiectasis cystic fibrosis vocal cord dysfunction persistent bacterial bronchitis
asthma triggers
exercise pollen house dust mites saliva on fur stress emotions - anger etc. insects cold air infections smoking pollution person specific
hypothetical causes of atopy
vitamin D hypothesis
antibiotics
dual allergen hypothesis - how you are exposed to allergens
hygiene hypothesis
treating chronic asthma and chronic urticaria
monoclonal antibody - omalizumab - anti IgE
treating chronic eczema
dupilumab
