Allergy Flashcards
What is an allergic disorder?
An immunological process that results in immediate and reproducible symptoms after exposure to an allergen.
What is an allergen?
Usually a harmless substance that can trigger an IgE mediated immune response and may result in clinical symptoms.
What is sensitisation?
Sensitisation is the detection of specific IgE either by skin prick testing or in vitro blood tests: occurs more often than allergic disease.
Which immunoglobulin is clinically significant?
IgE
What is the immune response to bateria, viruses and fungi?
Microbial PAMP > Recognition of conserved microbial structure > Th1, Th17 immune response
What is the immune response to helminths, allergens and venoms?
Recognition by change in function > Th2 immune response
In contrast to immune responses to bacteria, virus and fungi, immune responses to worms, venoms and allergens tend to react to tissue damage caused by these agents rather then relying on direct recognition of the pathogen. Worms, venoms and allergens are far more diverse than bacteria.
What are the signalling cytokines in a Th2 response?
GM-CSF, IL-25, IL-33, TSLP
Which mediate
Th9 cells, ILC2, Th2 Cells
What are the effector cytokines in a Th2 response?
Th9 cells, ILC2, Th2 Cells: IL-5, IL-9, IL-4, IL-13
Tfh2 cells: IL-4, IL-21
What are the effects of these effector cytokines?
Trigger eosinophil activation
Cause B cells to release IgE and IgG4
What do mast cells release?
Histamine
Prostaglandins
Leukotrienes
Proteases
What are innate lymphoid cells?
Innate lymphoid cells found at mucosal barriers (skin, respiratory and the gastrointestinal tract) which lack antigen specific receptors.
Respond to a number of inflammatory cytokines (IL-33, TSLP, IL-25) IL-1 and IL-12 family cytokines member.
How can CD4 ILC be classified?
ILC1, ILC2, ILC3, based on their cytokine production and transcriptional profiles with ILC1s, ILC2s, and ILC3s resembling CD4+ T helper (Th)1, Th2 and Th17/22 cells, respectively.
What do ILC2 secrete?
ILC2 secrete IL-4, IL-5, IL-9, IL-13 and amphiregulin (AREG).
Secretion of type 2 cytokines by ILC2 implicated in allergic asthma, allergic rhinitis AD, food allergy and eosinophilic oesophagitis. Amphiregulin paly an important role in epithelial barrier repair in skin and respiratory tract. In allergic disease overcome steady state inhibition exerted by tissue CD4 T regulatory cells.
How do CD4 Th2 cells contribute to an allergic response?
Distinct CD4 T subset characterised by expression of the lineage determining transcription factor GATA-3 and the signal transduction protein STAT-6
- Signature cytokines are IL-4, IL-5, IL-13
- Helps B cells to produce IgE (IL-4)
- Expands and activate eosinophils (IL-5)
- Stimulate mucous secretion (IL-13)
Role in host defense against helminths, parasites and tissue repair. Contribute to late stage tissue damage in allergic disease.
What is the role of eosinophils in an allergic response?
Host defence against parasites, bacteria and viruses.
Eliminate pathogens by secretion of cytotoxic granules, RNAase proteins and extracellular traps.
IL-5 is the key cytokine in the development and expansion of eosinophils.
Implicated in late stage tissue damage in atopic dermatitis, asthma, eosinophilic oesophagitis, and granulomatous disease
What is the function of IgE in an allergic response?
IgE binds to high affinity receptor (FceR1) on mast cells, basophils, eosinophils and DC.
IgE also binds to ‘low affinity’ (FceR2) receptor on above cells as well as B cells, respiratory and gastrointestinal epithelial cells.
Protection against helminth and parasitic infection. IgE induces mast and basophil degranulation associated with immediate hypersensitivity (allergic) reactions.
What is the role of mast cells in an allergic response?
2 main subtype in human: MC (Tryptase T) skin and MC (Chymotryptase CT) in airways.
Mast cells degranulation triggered by 1) IgE/IgG receptors which respond to antibody-antigen cross linking and 2) G-protein-coupled receptors which are ligands for soluble mediators (complement and drugs).
Role in immediate and late phase immune responses to helminths, bacteria. Play an important role in allergic disorders.
What are key mast cell receptors?
FcReR1(IgE)
FcgR1 and FcgR1IA (IgG)
MRGPRX2 (opiates, quinolones)
What does cross linking of bound IgE by antigen results in?
Release of pre-formed inflammatory mediators from granules (histamine)
Release and synthesis of lipid mediators (leukotrienes, prostaglandins)
Synthesis of pro-inflammatory cytokines
What does mast cell degranulation lead to?
Recruitment of soluble proteins and inflammatory cells to site of infection.
Increase in rate of lymphatic flow back to regional lymph nodes.
Smooth muscle contraction in lungs and gut (may help to expel pathogens) and activation of sensory neurons (itch, sneeze).
What factors promote IgE production?
Antigen dose
Length of exposure
Physical properties of allergen:
- Source
- Small water soluble proteins
- Carbohydrate
- Resistance to heat, digestive enzymes
Route of exposure
What is the difference between oral exposure compared to skin and respiratory exposure?
Oral exposure promotes immune tolerance whereas skin and respiratory induces IgE sensitisation.