Allergy Flashcards
Allergies are corresponded with Ig-E mediated diseases, how does an allergic reaction trigger?
Allergic reactions occur when antigen
is recognised by a sensitised individual.
Describe the two phases of the allergic reaction and results of them.
Early stage:
On the mast cell, once IgE antibodies binds to FcER, the allergens cross link to the antibodies and the mast cell activates. Then granules are released such as histamine, PGD2 and LTC
=> Itch
Vasodilatation
Plasma leakage
Bronchoconstriction
Mucus secretion
Nervous stimulation
Late Stage
Eosinophils release cytotoxic proteins which contributes to
=> Mucosal damage
Bronchoconstriction
Chronic inflammation
What is the role of T cells in the allergic inflammation?
The dendritic cell recieves an allergen and creates MHC class 2 + peptide complex. The Th-2 cell binds to the complex and activates.
It releases cytokines =>
- IL-4 which causes IgE antibodies to be released and activates more mast cells
- IL-5 contributes to the increased production of eosinophils
- IL-13 induces intestinal mucus sectretion & peristalsis
What are allergens?
They are proteins that have access to the immune system and often enzymatic activity. They require stability and soluability.
Explain what the Th1/Th2 paradigm is and why it is important
Both Th-cells have an important role in regulating the immunes systems response to pathogens, allergens, etc.
Th-1 cells are involved with cell mediated responses.
Th-2 cells are involved with humoral mediated responses.
It shows the balance of whether a th-1 cell or Th-2 will be used
Describe the IgE regulation
- The production of IgE is regulated by the activation of CD4+ T helper 2 (Th2) cells.
- Treg can inhibit the activation of Th2 cells and B cells, helping to prevent excessive IgE production
- There are cytokines that inhibit IgE production which come from T-cells or APC
IFN-γ (Th1, NK, Tc)
IL-12 (APC)
TGF-β (T-cell)
IL-10 (T-cell, APC)
Describe the Th1/Th2 regulation
Th1 Response Regulation:
The Th1 response is primarily regulated by cytokines, IFN-γ. These cytokines promote Th1 cell differentiation and IL-4 inhibits Th1 cell development.
Th2 Response Regulation:
The Th2 response is regulated by cytokines, like IL-4. These cytokines favor Th2 cell development and IFN-γ inhibits Th2 cell development.
The nature of the antigen itself can also influence the response, with some antigens favoring Th1 responses (e.g. intracellular pathogens, high antigen dose) and others favoring Th2 responses (e.g., allergens, low antigen dose).
Describe the helminth induced immunoregulatory network
Dendritic cells exposed to helminth antigens can exhibit tolerogenic properties:
=> promoting the differentiation of Tregs while inhibiting the activation of effector T cells. Helminth-induced Tregs can suppress both adaptive and innate immune responses.
=> Helminths release various molecules, which can induce the production of anti-inflammatory cytokines like IL-10 and TGF-β.
=> stimulate the production of IgE antibodies. While IgE is typically associated with allergic reactions, in the context of helminth infections, it can downregulate inflammation and help to expel the parasites.
What is the allergic march?
It describes the progression of allergic diseases, visible in the early childhood.
1. Atopic eczema
2. Asthma
3. Rhinoconjunctivitis
Why does microbial pressure contribute to down regulating the Th2 cell and an allergic reaction?
Allergy is mediated by Th2 cell response and the an inability to downregulate it. A high microbial pressure (exposure to bacteria, dirt etc) will promote Th1 cell response (intracellular pathogens). Th1 cell response (IFN-gamma ex) inhibits Th2 cell response and IgE production, which is why microbial pressure decreases allergy.
Why are young children susceptible to allergies
During pregenancy, IL- 4 and IL-10 are produced far more than IFN-y, which leads to Th2 cells being more prevalent in early life. Allergies in children come from the inability to down regulate the Th2 response. After growing up, there is an increase in the Th1 response.
What signals are needed for a B cell to start producing IgE?
- CD40-CD40L interaction. MHC class II allergen peptide interaction with T-cell. Cytokines IL-4, IL-13. IgE isotype switching is further enhanced by IL-9 produced by Th2 cells.
