13.1 Allergy & Hypersensitivity Flashcards
What is hypersensitivity?
- An overreaction to harmless molecules which results in an immune response that causes inflammation and tissue damage
- All hypersensitivities involve the adaptive immune system
Briefly explain the types of hypersensitivity & what they cause & the conditions they cause
Are allergies in society getting less common, the same, more common?
Allergy incidence is INCREASING
What are the causes of allergies?
Explain how 2 of them cause reactions?
- Inhaled – dust mite faeces, plant pollen
- Injected – insect venom, drugs
- Ingested – peanuts, shellfish
- Contact – plant oil, metal
Dose and site of exposure to allergens influences the type of immune response seen
- Pollen - Respiratory tract entry causing wheezing, sneezing,mucus production
- Peanuts – Ingested and absorbed into blood steam causing systemic oedema and vasoconstriction and anaphylaxis
What is the function of IgE?
And why are some pathogens less antigenic?
- The function of IgE induced responses is to get rid of multicellular parasites which are too large to be phagocytosed
- These pathogens often have antigens which are similar to our own and as such are inherently less antigenic.
What are some IgE promoted responses to (foreign) antigens?
What cells are involved in Type 1 hypersensitivity?
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MAST CELLS
- IgE becomes bound to FcεRI (Fc receptors) on mast cells
- One mast cell can have multiple IgE antibodies which recognise different antigens on their surface
- Release histamine and other mediators
- Tissue resident cells found predominantly in mucosal tissues near the surface and in connective tissues near blood vessels
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EOSINOPHILS
- Have IgE receptors
- Highly toxic response
- Numbers of eosinophils are increased by Th2 cells
- Small number in the blood, resident in connective tissues under mucosal surfaces
- Can synthesise cytokines and have preformed mediators including enzymes in their granules
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BASOPHILS
- Closely related to eosinophils
- Possibly key in initiating Th2 responses by secreting IL-4 and IL-13 at the beginning of an immune response
- Recruited during infections and activated by TLRs
- Evidence they can help switch B cells to IgE production
What is this?
A mast cell with antibodies
What is this?
An eosinophil
What is this?
A basophil
Explain how Type 1 hypersensitivity occurs and the 2 stages
Give examples of mast cell mediators that are performed in granules
Enzyme
Product: Tryptase, chymase, cathepsin G, carboxypeptidase
Biological effect: Remodelling of connective tissue
Toxic mediator
Product: Histamine, Heparin
Biological effect: Poison parasites, increase vascular permeability, cause smooth muscle contraction
Cytokine
Product: TNF-α
Biological effect: Promotes inflammation, stimulates cytokine production by cells, activates endothelium
Give examples of mast cell mediators that are sythesised during an allegic reaction
Cytokine
Product: IL-4, IL-13
Biological effect: Stimulate and amplify TH2 responses
Product: IL-3, IL-5, GM-CSF
Biological effect: Promote eosinophil production and activation
Chemokine
Product: CCL3
Biological effect: Attracts monocytes, macrophages and neutrophils
Lipid Mediator
Product: Prostaglandins D2 E2, Leukotrienes C4,D4 and E4
Biological effect: Cause smooth muscle contraction, increase vascular permeability, cause mucus secretion
Product: Platelet activating factor
Biological effect: Attracts leukocytes, amplifies production of lipid mediators, activates neutrophils, eosinophils and platelets
What are the routes of exposure to an allergen andd what they can cause?
How can allergy testing be done?
- By a blood test
- By skin prick testing
What is the hypothesis behind the increase in incidence of allergies?
HYGIENE hypothesis
- Allergy incidence is higher where parasite infections have been eliminated.
- In the last 150yrs with sanitisation of food and water, increased hygiene and medical advances allergies and autoimmunity have increased.
What does atopy mean?
A genetic tendency to develop allergic diseases
Explain why there are atopic individuals (details)
- Atopic individuals have high levels of IgE and eosinophils in the blood
- On chromosome 5 there is a cluster of genes for IL-4,3,5,9,12,13 and GM-CSF which are all involved in isotype switching, eosinophil survival and mast cell proliferation
- MHCII – Enhanced presentation of allergen peptides
- TCR alpha chain – Enhanced recognition of allergen peptides
- IL-4R receptor – Increased signaling from IL-4
- IL-4 – Variation in IL-4 protein expression.
- FcεRI – IgE binding
Explain type II hypersensitivity & give an example
- IgG antibodies bind to the surface of cells and cause their destruction
- Two ways this can be initiated:
- Intrinsic – antibodies to an antigen which we normally make
- Extrinsic – something from outside e.g. an infection or drug that attaches to a cell
- A simple example is incompatible blood transfusion:
Explain type III hypersensitivity & how it happens
- Can be local or systemic depending on the site of antigen exposure
- Preformed antibodies recognise and react to an antigen and form clumps called complexes
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Serum Sickness is a systemic reaction to injected foreign antigen e.g. anti venom and in some cases therapeutic monoclonal antibodies
- The antigen in serum sickness is removed and is self limiting.
- This reaction to a self Tyantigen could cause autoimmunity e.g SLE.
Briefly type IV hypersensitivity
- Mediated by antigen specific T cells reacting just as they would to a pathogen
- Is CD4 T cell dependent
- 2 types of type IV hypersensitivity:
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DELAYED-TYPE hypersensitivity
- Antigens = proteins
-
CONTACT hypersensitivity
- Antigens = haptens & small metal ions
Explain delayed type IV hypersensitivity
- Mediated by antigen specific T Cells which have previously been sensitised to the allergen
- An example is the tuberculin (Mantoux) test for latent tuberculosis
- This takes 24-72 hours to develop as the antigen is recognised and presented
- Antigen = proteins
- Causes: local skin swelling (e.g. erythema, dermatitis)
Explain contact type IV hypersensitivity
- Activation of CD4 or CD8 cells by highly reactive small molecules (called haptens) which penetrate intact skin
- Causes: local eepidermal reaction ee.g. erythema, intraepidermal abscesses
What are the steps in the hypersensitivity response to a transplant rejection & the types of recognition?
- Hyperacute (immediate) reaction – Type II – preformed antibodies e.g. mismatched blood donation
- Acute – Weeks to months – Type IV – T cell mediated immune response
- Chronic – Months to Years – Type IV – T Cell mediated immune response
- Even with precise MHC matching we have cell antigens which differ. This is why all transplants receive anti rejection drugs unless identical twins
- Polymorphic self proteins presented on the MHC can be recognised as foreign. These are more slowly rejected = Minor histocompatibility antigens
What is an alloantigen?
Antigens which differ between members of same species.
