Immunology of Allergy Flashcards
There are various types of allergies. Give a brief explanation of Allergic contact dermatitis and respiratory hypersensitivity.
An example of allergic contact dermatitis is breaking out in hives. Respiratory hypersensitivity includes allergic rhinitis and allergic asthma. This is when you breathe something from the air, which causes your airways to close up.
There are various types of allergies. Give a brief explanation of Xenobiotic allergy.
Certain drugs are associated with systemic allergic reactions (e.g. allergy to penicillin) that are sometimes reminiscent of autoimmune diseases. If the allergy is systemic it is very severe as this could lead to vasodilation and so blood pressure very low and you could die as a result.
There are various types of allergies. Give a brief explanation of food component allergy
This includes food additives implicated in adverse reactions, which in some cases take the form of an allergic response. Examples include allergies to sesame seed, peanuts and chocolate etc.
A recent example of this type of allergy is the sesame seed allergy case in pret.
Give examples of allergens
- Typical allergens include proteins in pollen, house dust mites, animal dander, foods, and chemicals like the antibiotic penicillin.
- It is not known why some antigens induce strong TH2 responses and allergic reactions whereas others do not.
- Two important characteristics of allergens are that individuals are exposed to them repeatedly
Do allergens induce the same immune response as microbes?
Unlike microbes, they do not generally stimulate the innate immune responses that are associated with macrophage and dendritic cell secretion of TH1- and TH17-inducing cytokines.
Allergen response is not the same as the response to a bacteria. It comes down to the differentiation of the helper T cells. The helper T cells release cytokines, promote B cell activation and killer T cell activation. There are two isoforms of the T helper cells; Th1 and Th2.
TH2 cells release the cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13, and these cytokines induce and perpetuate inflammation mediated by eosinophils and IgE-induced mast-cell degranulation
How did Küstner and Prausnitz demonstrate that it was possible to passively transfer immediate hypersensitivity to an allergen?
In 1921 Küstner, who was allergic to fish, injected his own serum into the skin of Prausnitz, who was allergic to grass pollen but not fish, and demonstrated that it was possible to passively transfer immediate hypersensitivity (the Prausnitz-Küstner or P-K test).
Due to the fact that serum was used there was no immune response. As he was able to passively transfer his own immune reactions to his friend, it shows that there is something tangible in your serum that is conferring allergy.
Prausnitz would also notice that an immediate wheal and flare occurred at the site of passive sensitization when he ate fish. This showed that intact fish allergen can be absorbed into the circulation. The wheal and flare was due to the fact under the skin there are mast cells. Mast cells release histamine, when it was in contact with the serum, and this causes the local area to wheal, to swell and flare up.
What causes the wheal and flare reaction?
The wheal and flare reaction is dependent on IgE and mast cells. This is what as transferred in the PK test. In vaccinations it is IgM or IgG (as well as other immunology cases), but allergies is (occurs in the sensitization phase) dependent on IgE and mast cells. The immediate wheal and flare reaction is followed 2 to 4 hours later by a late-phase reaction consisting of the accumulation of inflammatory leukocytes, including neutrophils, eosinophils, basophils, and TH2 cells.
What is the difference in how antibodies work in allergy and non-allergy reactions?
Normally - Antibodies work through the promotion of phagocytosis, antibody dependent cellular cytotoxicity. It does this by the antibody binding to the microbe of the pathogen associated molecular pattern at the top and at the bottom it binds to the Fc receptors on white blood cells (neutrophils, macrophages, monocytes and dendritic cells).
In Allergy - IgE cannot bind to macrophages and monocytes, this is as it will not fit, only IgG will. IgE, which is found in the serum can bind to mast cells, eosinophils and basophils but IgG cannot. First you get sensitisation phase where the antibody binds to the mast cells. The cross-linking of the IgE binding to the receptors on the mast cell will cause the mast cell to de-granulate. This causes the release of histamine/prostaglandins, which causes and immediate reaction in the localised area of inflammation. This leads to vascular leakiness, swelling redness and itchiness.
What are the four types of hypersensitivity reactions?
In type I, mast cells bind IgE via their Fc receptors. On encountering allergen the IgE becomes cross-linked, inducing degranulation and release of mediators that produce allergic reactions.
In type II, antibody is directed against antigen on an individual’s own cells (target cell) or foreign antigen, such as transfused red blood cells. This may lead to cytotoxic action by NK cells, or complement-mediated lysis.
In type III, immune complexes are deposited in the tissue. Complement is activated and polymorphs are attracted to the site of deposition, causing local tissue damage and inflammation.
In type IV, antigen-sensitized T cells release lymphokines following a secondary contact with the same antigen. Cytokines induce inflammatory reactions and activate and attract macrophages, which release inflammatory mediators.
What immune cells are activated in an allergen response in comparison to a bacterial response?
Allergen response:
- Eosinophils
- Mast Cells
- Basophils
- Th2 CELLS- this is predominant.
- IgE antibody- this binds to the mast cells and cause them to de-granulate. Th2 cells predominantly helps the B cells become plasma cells and make IgE.
- Cytokines produce IL-4, IL-5,1L-13 (IL stands for interleukin)
All these things can be found in the blood which allows an allergic response to be identified with a simple blood test.
Bacterial response:
- Neutrophils- this carries out phagocytosis and recognises pathogen associated molecular patterns
- Macrophages- this also carries out phagocytosis and recognises pathogen associated molecular patterns
- Th1 Cells- predominant (shown in green below.) This predominantly helps cytotoxic T cells.
- IgG antibody
- IFNg (interferon gamma), TNFa (TNF alpha)
Describe the process of allergen exposure to an immune system and the subsequent cascade of events.
- Here there is exposure to an allergen it will be phagocytosed.
- Antigen receptors specific for the allergen, bind, internalise & process & present the antigen in MHCII. (This happens in phagocytosis.)
- The B cells will communicate with the Th2 cell.
- When the B cells are activated there is class switching occurs. This is when the B cell makes IgE instead of IgG.
- This occurs due to IL-4 and IL-13, which are responsible for the switching of Ig to e and the subsequent production of IgE.
- IL-4 is also involved in B cell differentiation & growth
- The IgE is made by the plasma cells and they bind to mast cells as well as basophils and eosinophils.
- This activation of allergen-specific T helper 2 (TH2) cells and IgE synthesis is known as allergic sensitisation
- When the IgE bind to the mast cells, it undergoes cross-linking which induces de-granulation and this produces your allergic response.
- This is due to the release of histamines, prostaglandins, leukotrienes, cytokines and chemokines.
- This is known as the triple response which is reddening, wheal and flare.
Stopping the production of IgE, will prevent the activation of the mast cell and so allergic reaction will not occur. The production of IgE can be done through the use of T cells.
How do allergens affect airways and how does this affect asthmatics?
Airway narrowing: mucosal oedema, smooth- muscle constriction, mucus hyper-secretion and epithelial-cell shedding into the airways. This then prevent efficient gas exchange.
Chronic inflammation might lead to permanent structural changes from the release from leukotrienes, prostaglandins etc), such as smooth- muscle hypertrophy and sub-epithelial fibrosis. This can prevent you from being able to vasodilate again.
When you give noradrenaline, what you are trying to do it increase blood pressure, which will cause vasoconstriction and so bronchodilation.
Why do we become sensitised to allergens?
- One of the theories of allergies is that removal of the food from your diet makes you hypersensitive to it. For example, in the 1990s a large amount of pregnant women stopped eating peanuts causing peanut allergy to rise.
- Environment- condition mucosal tissues of the immune system to produce IL-4 (Predisposes Th2 response)
- Regulation of immune response through Th1 is defective
Prevalence of allergy seems to be inversely proportional to infection. So this means that as the levels of vaccination has increased, there is an increase in autoimmune diseases as seen in figure B.
What is the hygiene hypothesis?
- Early childhood infections provide a TH1 stimulus. This is where they are permanently stimulated, as the more infections you have the more you train your thymus to have these Th1 cells
- For the TH2-skewed immune system of humans (this is the fact that naturally you have more Th2 cells, but as you get infections the number of Th1 and Th2 cells even out.)
- In Western countries, the reduction in the number of childhood infections means that the immune system lacks this TH1 stimulus and continues to maintain a TH2 bias, which results in an increased risk of developing allergy and asthma.
- The reduction of infections is due to the increased levels of hygiene.
IgE was specific for worms and parasites- those that have helminth infections have a low incidence of allergy. But also results in a TH2-biased immune response, where there is high levels of TH2 cells.
If you have high IgE, why don’t you get an allergic reaction?
This is because the IgE will preferentially bind the parasite rather than the allergen and hence does not cause an allergic reaction.
What are some advantages of a chronic worm infection?
- Parasites elicit high non-specific IgE-
- Saturates FCeRI and reduces type I hypersensitivity. This is when you have an allergy and a parasitic worm infection simultaneously.
- The IgE binds to the parasite preferentially and this binding is associated with high levels of a cytokine called IL-10
- This means that you can find high IL-10 in chronic worm infections
- IL-10 induced deactivated T regulatory cells - Subjects receiving allergen immunotherapy- high IL-10
- The activation of the eosinophils/mast cells causes degranulation, which will act on the parasitic worm. The parasitic worm is 6m long and so too long for it to be phagocytosed
- However, evolutionary we do not get parasitic infections anymore so the IgE targets allergen as there is no parasitic worm present.
