Allergy Flashcards
What is type I hypersensitivity?
IgE mediated degranulation of mast cells - immediate type hypersensitivity
Peaks at 30 minutes
e.g. allergic rhinitis, allergic asthma, urticaria
What is type II hypersensitivity?
IgG mediated, a cytotoxic reaction e.g. a drug allergy
Peaks at days
Complement lysis/ADCC: Complement Lysis: When the antibodies bind to the target cells (e.g., red blood cells or platelets), they activate the complement system. This is a group of proteins in the blood that, when activated, can form a complex called the membrane attack complex (MAC). The MAC forms holes in the cell membrane, leading to lysis (breaking open) and destruction of the target cells.
Antibody-Dependent Cellular Cytotoxicity (ADCC): In ADCC, the antibodies bound to the target cells can recruit natural killer (NK) cells, macrophages, or neutrophils. These immune cells have receptors for the constant region of the antibody (Fc region) and, when they bind to the antibody-coated target cells, they release cytotoxic substances that kill the targeted cells.
What is Type III hypersensitivity?
IgG mediated
Immune complex reaction - complement activation e.g. allergic vasculitis
What is type IV hypersensitivity?
IgG and T-cell mediated, delayed type hypersensitivity
peaks at 48-72 hours
e.g. allergic contact eczema
Name the common allergens in Type I hypersensitivity.
Small soluble proteins
Proteases
What are some diseases caused by type I hypersensitivity?
Allergic rhinitis
asthma
anaphylaxis
What are the organ manifestations of type I hypersensitivity?
Skin mucosa- 45%
Respiratory tract - 25%
GI tract - 20%
CVS - 10%
What is the mechanism of type II hypersensitivity?
IgG or IgM bind to cell-surface antigens -> complement activation -> cell lysis
What does the enzyme Der P1 do?
It cleaves occludin in tight junctions and enters mucosa for DCs to take up for antigen presentation and TH2 priming
describe protease-mediated Type I IgE hypersensitivity.
1) Der p 1 enzyme cleaves occludin in tight junctions and enters mucosa
2) Der p 1 taken up by DCs for antigen presentation and TH2 priming
3) DC primes cell in lymph node and TH2 cell induces B-cell class-switching to IgE production
4) Plasma cell travels back to mucosa and produces Der p 1-specific IgE antibodies
5) IgE binds to FceRI receptor on mast cells
6) Der p 1-specific IgE binds mast cell and Der p 1 triggers mast cell degranulation (conformational change)
6) Mast-cell granule contents cause allergic symptoms
Which allergens of Der p that are proteases?
1, 3, 6, 9
Which receptor has high affinity for IgE?
Fc-epsilon-RI
what are the effects of histamine and heparin?
toxic to parasites
increase vascular permeability
cause smooth muscle contraction
anticoagulation
what cytokines stimulate and amplify the TH2-cell response?
IL-4 and IL-13
Which cytokines promote eosinophil production and activation?
IL-3, IL-5
What is the effect of TNF-alpha?
promotes inflammation
stimulated cytokine production by many cell types
activates endothelium
what is the biological effect of chemokine CCL3?
attracts monocytes, macrophages and neutrophils
What are the biological functions of prostaglandins D2, E2 and leukotrienes C4, D4, E4?
smooth muscle contraction
chemotaxis of eosinophils, basophils and TH2
increase vascular permeability
stimulate mucus secretion
bronchoconstriction
what is the effect of platelet-activating factor?
attracts leukocytes
amplifies production of lipid mediators
activates neutrophils, eosinophils and platelets
what are the effects on the GI tract of mast cell activation and granule release?
increased fluid secretion, increased peristalsis
expulsion of GI tract contents -> diarrhoea, vomiting
what are the effects on the eyes, nasal passages and airways of mast cell activation and granule release?
decreased diameter, increased mucus secretion
congestion and blockage of airways (wheezing, coughing, phlegm)
swelling and mucus secretion in nasal passages
what are the effects on the blood vessels of mast cell activation and granule release?
increased blood flow and permeability
increased fluid in tissues causing increased flow of lymph to lymph nodes
increased cells and proteins in tissues
increased effector response in tissues
hypotension potentially leading to anaphylactic shock
what is another term for vascular leakage?
oedema
what are common allergens of systemic anaphylaxis?
drugs, venom, food, serum
what is the biological response to systemic anaphylaxis?
oedema, increased vascular permeability, laryngeal oedema, circulatory collapse, death
what are common allergens for acute urticaria?
animal hair, insect bites, allergy testing
what is the biological response to acute urticaria?
local increase in blood flow and vascular permeability
oedema
what might be seen in the airways of someone with chronic asthma?
collagen deposits - remodelling - also may see eosinophils and mast cells in the lung
what is T-bet?
a transcription factor that controls T-cells
Which mutant triggers cold-induced urticaria?
NLP3 mutants - activates the inflammasome
How does vibrational urticaria occur?
The EMR2 GPCR is a mechanosensor so can measure shear stress - overly sensitive mechanotransduction induces mast cell degranulation
what are leukotrienes an example of?
lipid mediator
what do eosinophils do?
kill parasites via reacting towards opsonised parasites
how would inducing T regulatory cells be a good treatment for allergy?
would switch off TH2 cells, as well as blocking IL4 and IL14 to skew TH2 response
what is the cleanliness hypothesis?
more allergies due to being brought up in a sterile/clean environment
children will therefore not encounter as many pathogens and will grow up not to have as good of a TH1 response -> TH1 turns off TH2
