Hypersensitvity Type I - Hunter Flashcards
What is immunopathology?
When the immune system itself is the primary cause of disease. This is present to some extent in every infection.
Type I Hypersensitivity (TIH) is mediated by what antibody?
IgE response to extrinsic substances. It is a disease following a response by the immune system to an otherwise innocuous antigen.
Type I hypersensitivity is also called what?
Immediate hypersensitivity since some responses occur within seconds - however there may also be some delayed responses.
What type of antigens are involved in TIH?
Usually small, soluble antigens.
What cell types are involved in TIH?
Mast cells and eosinophils.
What are some examples of TIH?
Allergic rhinitis, asthma, systemic anaphylaxis.
What is the normal physilogical function of IgE, eosinophils and mast cells?
This system evolved to be the principle immune defense against metozoan parasites (worms). Normally, cross-linking of IgE on mast cells leads to release of mediators that promote the expulsion of parasites.
What can elicit the same response as a metozoan parasite in some cases?
Certain innocuous environmental materials or allergens in a low dose delivered across a mucosal surface.
TIH reactions are typically induced by what?
Extrinsic allergens that are inhaled - such as pollen, dander, mold OR injected materials such as insect venoms, vaccines and drugs OR ingested material such as food and orally administered drugs.
In the case of an actual metozoan parasite what is the chain of events?
- Dendritic cell encounters antigen and produces IL-4, IL5, IL-9 and IL-13
- A TH0 cell under these cytokines will differentiate into a TH2.
- immune system mounts a response, including producing antibodies.
- The differentiation into the TH2 direction is needed for the allergic response also.
Is there a genetic component to allergies?
Yes, you must have an MHCII that can display the allergen protein.
What is necessary for allergic responses to occur?
- You must have an MHCII that can display the allergen.
- You must have a TH2 deviated environment.
- An allergen specific B cell binds to and internalizes the allergen and presents it in MHCII to CD4 TH2 cells that produce IL-4.
- The B cell will bind to the TH2 cell via CD40L/CD40 and will respond to IL-4 via its IL-4 receptor and this promotes isotope switching to IgE.
What is special about an IgE immunoglobulin?
It is cytophilic, it can bind via its Fc region to the Fcepsillon receptor on Mast cells, basophils and eosinophils even without interacting with antigen first.
Do mast cells and basophils express the Fc epsilon receptor constitutively?
Yes, but eosinophils must be activated first.
Does an allergic response occur after the first exposure?
No, the primary exposure is what sensitizes the person.
- The allergen enters the body and interacts with APC with a specific MHCII.
- The APC releases cytokines that cause a TH2 deviated environment.
- Thelpers interact with B cells of the same specificity. The B cell is activated and proliferates and starts secreting IgM.
- TH2 helpers secrete lots of IL-4 and this leads to the B cell switching to IgE production.
- The IgE molecules bind to mast cells.
- On second exposure the IgE are triggered via cross-linking of antigen to release granules with histamine and start the inflammatory processes.
Where are mast cells found?
In the skin, in all mucosal areas, and lining the blood vessels.
What 3 pathways are triggered by IgE crosslinking on Mast cells?
- granules with preformed mediators are exocytosed - in seconds to minutes - leading to vascular dilation and tissue damage.
- prostaglandins andleukotrienes are released - in minutes to hours - leading to vascular dilation and smooth muscle contraction.
- there is transcription al activation of cytokine genes - and cytokines are released - in hours. These cytokines lead to inflammation and leukocyte recruitment.
What determines the type of IgE mediated allergic reaction?
The dose and route of allergen administration. For example inhalation can cause asthma while IV administration can cause anaphylaxis.
Can enzymes act as allergens?
Yes, For example Der p1 is an enzyme in dust mite feces that cleaves occludin in tight junctions so that it can enter the body. Once inside it acts as an allergen.
What is Eosinophilia?
Eosinophilia occurs when either a large number of eosinophils are recruited to a specific site in your body or bone marrow produces too many eosinophils.This can occur with allergies.
Eosinophilia can be induced by what cytokine?
Il-5. This cytokine goes to the bone marrow to increase the production of eosinophils. They are then recruited to to sites of inflammation via chemokines (Eotaxins 1 and 2 also called CCL11). These chemokines bind to eosinophil CCR3.
Do eosinophils have the Fc epsilon receptor?
Yes, but only in their activated state when they get to the tissues.
What is the normal serum level of eosinophils?
About 1-3% - so if they are elevated then this can be diagnostic for a parasite infection or for chronic HTI.
Does Asthma have both acute and chronic components?
Yes.
- The acute response - inflammatory mediators causing increased mucus, smooth muscle contraction leading to airway obstruction and recruitment of other cells from circulation including TH2 cells.
- The chronic response - caused by cytokines and eosinophil products. This leads to airway remodeling where the damage heals by fibrosis and scarring. This in turn leads to COPD and the airway becomes hyperactive responding to innocuous things like cold weather.
