Immunology (Liz - Hypersensitivity) Flashcards
What is hypersensitivity?
Unfavourable exaggerated action of the immune response
What are the 4 types of hypersensitivity?
Type I - IgE-mediated hypersensitivity
Type II - IgG or IgM mediated cytotoxic hypersensitivity
Type III - Immune complex mediated hypersensitivity
Type IV - Cell-mediated hypersensitivity
What is are the typical manifestations of type I hypersensitivity?
Systemic and localised anaphylaxis such as hay fever, asthma, hives, food allergies and eczema
What is the structure of the IgE antibody?
- Has an extra constant region domain (CH4) like IgM but no hinge region
What does IgE bind to?
- Fc receptors on the membranes of blood borne basophils and tissue mast cells in the CH3 domain of the IgE molecule (look at slide 5 for clarification)
Describe both the first and subsequent allergic response to ragweed pollen
First contact:
- Ragweed antigen binds to B cells
- B cell differentiates to a plasma cell that produces large amounts of ragweed IgE antibody
- IgE molecules attach to mast cells
Subsequent contact:
- IgE-primed mast cells release molecules that cause sneezing, runny nose, watery eyes etc
Describe how IgE antibodies bind to the mast cell and what this triggers the mast cell to do
- Bind to alpha chain of high affinity Fc receptors Fc(epsilon)RI on mast cell
- Activated mast cells secretes IL-4 which causes B cells to class switch
- B cells start to produce antigen-specific IgE instead of IgG
Which part of the FcR causes signal transduction?
The gamma and beta chains
What signal transduction occurs as a result of IgE/FcR binding?
- First, activation of tyrosine kinases
- Tyrosine kinases activate both protein kinase C (PKC) and mitogen-activated protein kinases (MAPK)
- Both activate transcription factors such as NFkB that regulate cytokine production (e.g IL-4)
- PKC activates phospholipase D (PLD) which causes degranulation
- MAPK activates phospholipase A (PLA) which causes production of leukotrienes and prostaglandins
(See diagram for clarification)
Why are leukotrienes and protaglandins important?
Lipid mediators of inflammation
- cause vasodilation and increased vascular permeability
What is the wheal and flare reaction?
The reaction to allergins injected into the skin, in which blanched wheals appear surrounded by redness
How are people tested for whether they’re allergic to particular allergens (grass etc)
Intradermal injection of allergen
- Measure weal diameter 15-30 mins after exposure
In tern of food allergies, what is the response in nonallergic individuals vs allergic individuals
Nonallergic individuals:
- Food allergens cross the gut epithelium and are taken up into APCs
- APCs present food antigen to T cells and induce tolerance via the production of T reg cells
Allergic individuals:
- Allergic individuals have larger gaps between intestinal epithelial cells
- Once present, food allergen-specific IgE antibodies help transcellular food uptake via low affinity binding to CD23 on epithelial surface
- Allergen taken in by APC
- APC causes production of Th2 cells that signal (via cytokines e.g IL-4) to B cells to produce IgE antibodies
What factor influences Treg vs Th2 induction pathways
The gut microflora
- TLRs on APCs binding to PAMPs can induce Treg formation over Th2
What is the hygiene hypothesis?
That exposure to pets and farmyard animals etc in childhood can protect children from food allergies
- due to early exposure to microbes
- Drives the immune system into a general state of Th1 responsiveness and no allergy development
Allergic responses to inhaled antigens e.g grass pollen can be divided into what 2 phases?
1) Intermediate phase
2) Late phase
What is an asthmatic response measured using?
Peak expiratory flow rate (PEFR)
What occurs to PEFR during an asthmatic response and why?
Falls
- Due to rapid histamine release from mast cells
- Causes smooth muscle contraction
Describe what causes the intermediate and late phase responses and when each happens
Intermediate:
- happens minutes after antigen inhalation and subsides after an hour
- Due to mast cells releasing histamine
Late:
- 6-8 hours after antigen challenge
- Response in the lung
- Due to migration of inflammatory leukocytes to the lungs attracted by chemokines
How do dust mite fecel pellet allergens penetrate the epithelial barrier?
Have a proteolytic enzyme, Der p1, that cleaves occludin, a protein that helps maintain tight junctions
How does the dust mite allergic response occur?
- Der p1 taken up by dendritic cells for antigen presentation and Th2 priming
- DC migrates to lymph node and primes naive T cell to become Th2 cell
- Th2 cell incudes B-cell switch to IgE production
- Plasma cell tavels back to mucosa and produces Der p1-specific IgE antibodies which bind to mast cells
- Mast cell degranulation = allergic symptoms
Development of atopic allergic diseases is a result of what 2 factors?
- Genetic susceptibility
- Environment
Describe the interaction between genetics and environment that give and no not give allergic responses
Atopic:
HIGH genetic susceptibility with ‘HYGIENIC’ environment - gives mainly Th2 responses
Non-atopic:
LOW genetic susceptibility with ‘LESS HYGIENIC’ environment gives Th1 responsiveness
Almost all allergy triggers are from what type of organism?
Eukaryotic (plants,animals, fungi)
Only 1% from bacteria
