wk2: AED - Immunopath Allergic Response Flashcards
Outline the 6 steps for the general mechanism of allergic response
- First exposure to allergen
- Antigen activation of TH2 cells + stimulation of IgE class switching in B cells
- Production of IgE
- Binding of IgE to FCeR1 on mast cells (sensitises them)
- Repeated exposure to allergen
- Activation of mast cell: release of mediators
What 3 mediators do activated mast cells release?
Vasoactive amines
Lipid Mediators
Cytokines
In what phase of allergic reaction do mast cells release vasoactive amines and lipid mediators? (When)
Immediate hypersensitivity reaction (minutes after repeated exposure to allergen)
In what phase of allergic reaction do mast cells release cytokines? (when)
Late-phase reaction (2-4 hours after repeated exposure to the antigen)
Why are TH2 cells important for the allergic response?
Because they drive IgE production
Describe the 2 phases of an allergic reaction
Immediate phase, followed by late-phase reaction which involves recruitment of eosinophils (sometimes neutrophils)
What mediates activation of mast cells?
IgE antigen complex
By what process is degranulation triggered?
Transduction
What does a mast cell release when it degranulates? [3]
Histamines, Proteases, and Chemotactic factors (ECF, NCF)
What part of the mast cell is responsible for the release of secondary mediators?
Membrane phospholipids
What secondary mediators do membrane phospholipids drive?
drives the arach. acid pathway and platelet-activating factor
Where is the H1 receptor expressed? What does activation of the H1 receptor cause?
In nerve terminals (e.g. sensory nerves of conj.). Activation cases nerv stimulation - e.g. conjunctival itching
Where is the H2 receptor expressed? What does activation of the H2 receptor cause?
In the smooth muscle of blood vessels (e.g. walls of conj. vessels). Activation causes vasodilation - e.g. cause of conj. redness
Which phase of allergic reaction is more severe? Immediate or Late-phase
Immediate is more severe
What is a histopathological sign of an allergic reaction?
Eosinophils present in the epithelium
What is the difference between what neutrophils and eosinophils ingest?
Neutrophils ingest cellular debris, Eosinophils ingest antigen-antibody complexes
Does the presence of presence of eosinophils mean there’s a parasitic infection?
Not always. In non-parasitic infections, the eosinophils come in thinking there’s a parasite even if there isn’t
What happens to a parasite before being ingested by eosinophils?
It gets coated in antibody: marking it for the eosinophil to come eat
What do eosinophils do in a mast cell/IgE-mediated response to small antigens?
They arrive at the site but then are bystanders because there are no antigen-antibody complexes for them to ingest
What type of cell can be used as a diagnostic tool for IgE-mediated responses?
Eosinophils
What is the difference between delayed hypersensitivity (Type IV) and an allergic response?
DTH is not IgE mediated or immediate
Note: some drugs such as penicillin or atropine can stimulate immediate IgE reactions, however most drugs show delayed response - not clear why
What 3 different types of eye discharge are there that can help guide our diagnosis
Pus discharge
Mucus discharge
Watery discharge
How can ocular IgE-mediated allergic response present clinically? [9]
Intense Itchiness, Red eye, Conjunctival chemosis , Blurred vision, Mucus discharge, Lid thickening , “Cobblestone” papillae
Limbal infitrates, SPK, Corneal ulcer
Why might a patient with IgE-mediated allergy experience conjunctival chemosis?
B/c of the oedema that occurred
In what IgE-mediated allergic reaction would patient most likely to experience lid thickening?
papillary conjunctivitis
How can ocular IgE-mediated allergic response lead to the development of SPK (superficial punctate keratitis/keratopathy)?
via mechanical trauma from the cobblestone papillae scratching the inside of the eye
What is SPK (superficial punctate keratitis)?
An eye disorder caused by death of small groups of cells on the surface of the cornea. Causes the eyes to become red, watery, sensitive to light and possible vision reduction
What are the 4 main ways ocular allergies may present?
Acute rhinoconjunctivitis or allergic/perennial/seasonal conjunctivitis (ARC)
Vernal keratoconjunctivitis (VKC) (seasonal)
Atopic keratoconjunctivitis (AKC)
Giant papillary conjunctivitis (GPC)
Name 3 clinical signs of VKC (vernal keratoconjunctivitis)
Giant papillae on superior tarsal conjunctiva
Gelatinous limbal lesions
Mucous discharge
Is VKC acute or chronic?
Chronic/recurring
When does VKC occur?
Seasonal, but can be perennial (especially in warmer climates - i.e. it’s rarer in cooler climates)
Describe the gender distribution of incidence of VKC
In youth: mostly males get it
In adults/older: both genders equally get it
How successful are anti-allergy medications in the treatment of VKC?
Often unsuccessful
What is the initiating factor for VKC?
Abnormal TH2 cells making the body hypersensitive to the antigen
What type of hypersensitivity is VKC?
Mixed: Type 1 and IV
What do you find in the tears of a patient with VKC?
Large numbers of eosinophils/neutrophils along with TH2 lymphocytes
How high are IgE levels in the tears and plasma of a patient with VKC? What does this suggest?
Very High. Suggests systemic involvement
What do conjunctival biopsies on patients with VKC reveal?
large amounts of TH2 CD4+ lymphocytes
What is the role of TH2 lymphocytes?
stimulate plasma cells and stimulate production of IgE by B-lymphocytes
What does a biopsy of the giant papillae of VKC patients indicate/show?
High concentrations of mast cells (many of which are degranulating)
What does a conjunctival biopsy of VKC patients show?
eosinophil invasion into oedematous stroma from vasculature
What does the invasion of eosinophils into the stroma of VKC patietns lead to? (3)
Thickened epithelium (b/c epithelium undergoing hyperplasia) Folds in epithelium develop Start to get crypts, where epithelium involutes into the tissue (as the folding gets worse)
What does the tarsal histology of VKC patients reveal? (3)
Epithelial ingrowth forming pseudo-glandular arrangements of goblet cells Mucin secretion (possibly due to histamine) Mucin plugs forming in pseudo-glands
What are “pseudo-glands”?
When the epithelium folds in the tissue, you get these pseudo-glands that apear to be glands but are not. They are actually made up of goblet cells, which are secreting truckloads of mucin, which are dumped out onto the ocular surface and tear film
What does histopathology of VKC at the limbus reveal? (i.e. the limbal form of VKC) [3]
Biopsy of gelatinous limbal lesions in VKC shows marked inflammatory cell infiltration, oedema, and expression of eotaxin and RANTES in conjunctiva
What does histopathology of VKC at the cornea reveal? (i.e. the corneal form of VKC)
Subepithelial eosinophils/toxic eosinophil protein deposition
In the cornea of VKC patients, where do most of the eosinophil proteins deposit?
At areas of total epithelial ulceration
What is the main cause of GPC (Giant Papillary Conjunctivitis)?
Almost exclusively a result of CL wear (can occur with any type of CL)
Is GPC a mechanical condition or type 1 hypersensitivity?
it has both a mechanical component and type 1 hypersensitivity (is partly IgE mediated)
How does the tarsal conjunctiva in GPC patients have in common to VKC/AKC? (2)
tarsal conjunctival tissue is loaded with many types of inflammatory ells and tear IgE is particularly high (suggesting allergic response)
What does biopsy of conjunctiva in GPC monkey show? (2)
large numbers of IgE positive plasma cells in stroma and mast cells in epithelium
How is the biopsy of giant papillae in GPC similar to VKC/AKC? [3]
shows inflammatory infiltrate (not wholly eosinophilic), oedema, and formation of epithelial pseudo-glands (which are seen to contain goblet cells)
What treatments are useful for IgE-mediated response? (2)
Mast cell stabilisers, antihistamines
What treatments are useful for controlling cellular response in hypersensitivity? (2)
steroids, NSAIDS
