A-IV Allergies Flashcards
Hypersensitivity reactions
Exaggerated immune response that causes deleterious effects and damage
Type I hypersensitivity
Mediated by IgE and the activation of mast cells, resulting in an immediate reaction.
Type IV hypersensitivity
T-cell mediated, also known as delayed type hypersensitivity (DTH), involving activated T-cells and macrophages.
Allergy
A disease caused by an excessive response to a foreign antigen, involving Type I and IV hypersensitivity.
Autoimmune disease
A disease caused by a failure of self-tolerance, involving Type II and III hypersensitivity.
IgE
An antibody produced in response to allergens. Four constant domains (Fc), no hinge, very potent
FcεRI
The Fc receptor for IgE, found on mast cells in tissues and basophils in blood
Allergens
Examples include proteins in pollen, house dust mites, animal dander, and foods. They are often characterized by low molecular weight and high solubility.
Mast cells
Immune cells that carry allergen-specific IgE on their surface via FcεRI. Upon allergen binding, they release granules containing histamine. They are located near blood vessels, nerves, and beneath the epithelium.
Histamine
A mediator released from mast cell granules that causes smooth muscle contractions and increased vascular permeability.
Anaphylaxis
A severe allergic reaction characterized by restriction of the airway due to mast cell-derived mediators, leading to cardiovascular collapse and potentially death.
Asthma (in allergy)
An allergic condition involving muscle tightening, lining swelling, and excess mucus in the airways.
Delayed type hypersensitivity (DTH)
An allergic reaction mediated by activated T-cells, leading to a feedback loop with macrophages. Examples of allergens include insect venom and poison ivy.
Allergen desensitization / Immunotherapy
A treatment for allergic disease involving injecting patients with escalating doses of antigen to change the immune response from IgE to IgG and induce Tregs.
Qhat characterizes a Type I hypersensitivity reaction?
Type I hypersensitivity is induced by antibodies, specifically IgE, which leads to the activation of mast cells and an immediate reaction with symptoms appearing within minutes.
What is the main characteristic of a Type IV hypersensitivity reaction?
Type IV hypersensitivity is T-cell mediated and is also known as delayed type hypersensitivity (DTH), involving the activation of T-cells and a feedback loop with macrophages.
What is the role of IgE in allergic reactions?
IgE is produced in response to allergens. It binds to the Fc receptor for IgE (FcεRI) which is found on mast cells in tissues and basophils in blood. When IgE on mast cells connects to an allergen, it triggers the release of granules containing histamine.
Can you provide some examples of allergens?
Examples of allergens include proteins in pollen, house dust mites, animal dander, and foods.
What are some key characteristics of allergens?
Allergens are often characterized by low molecular weight and high solubility in body fluids. They can also be enzymes. Importantly, they are generally not polysaccharides unless connected to proteins, in which case they can have a hapten-carrier effect. They also do not stimulate innate immune responses directly but may drive towards the Th2 pathway and IL-4 production, stimulating mast cells. They do not have PAMPs.
What are the primary actions of histamine released during an allergic reaction?
Histamine release leads to smooth muscle contractions and increased vascular permeability.
Describe the process of mast cell activation in an allergic reaction.
Mast cells carry allergen-specific IgE on their surface, bound to FcεRI. When this IgE connects to an allergen, the mast cell is activated, and granules containing histamine are released.
What are some of the mediators stored in mast cell granules?
Mast cell granules contain histamine, heparin and/or chondroitin sulfate, and proteases.
What are some of the cytokines produced and released by mast cells after activation?
Mast cells synthesize and release cytokines such as IL-4, IL-13, and IL-33, which promote Th2 differentiation and IgE production; IL-5, which promotes eosinophil production and activation; and TNF-alpha, which contributes to inflammation.
What are the roles of leukotrienes and prostaglandins in allergic reactions?
Leukotrienes (like LTC4) cause bronchoconstriction, while prostaglandins (like PGD2) act as vasodilators and bronchoconstrictors.
How do connective tissue mast cells and mucosal mast cells differ in terms of location and contents?
Connective tissue mast cells are found in vascularized connective tissue and skin and their granules contain tryptase, chymase, cathepsin G-like protease, and carboxypeptidase. Mucosal mast cells are located in the intestinal mucosa and lung and their granules mainly contain tryptase.
What triggers basophil activation in allergic reactions?
Basophil activation is triggered by antigen binding to IgE bound to FcεRI on the cell surface.
What is the role of Th2 cells in allergy?
Th2 cells produce IL-4, which activates B-cells to secrete IgE; IL-5, which promotes the activation and recruitment of eosinophils; and IL-13, which activates the epithelium.
What is celiac disease?
Celiac disease is described as an immune response to α-gliadin, found in wheat, oat, etc. It involves CD4+ cells, plasma cells, and macrophages infiltrating the upper small intestine, leading to the destruction of villi. It is also noted that both autoimmune and allergic reactions are involved, with the presence of IgA autoantibodies to transglutaminase being a diagnostic marker.
How are mast cells produced?
From progenitor cells in bone marrow, then they migrate directly tissue as immature cell and differentiate in the tissue
How is the Th2 activated?
Mast cells release IL-4, IL-13, TNF-alpha, which causes Th2 differentiation (and also inflammation)
How does the compliment system trigger mast cells in connective tissue?
C5aR1 (receptor) that can be activated by C5a. Also has C3aR
Which mast cells have TLRs?
Mucosal mast cells
Describe different pathways of mast cell activation
DC present allergen for Naive T-cell -> differentiation to Th2 cell
-> IL-4 cause B cells to isotype switch to IgE -> Binds to FcεRI -> binding of antigen to FcεRI cause granule release
-> IL-9 activates mast cells to release granule
What is a non-atopic reaction?
When mast cells are activated independently of IgE, such as with chemokines, complement.
What are some causes of allergy?
Genetic susceptibility (atopic), too clean environment (non-atopic)
True or False: Type I hypersensitivity reactions are mediated by IgG antibodies.
False; they are mediated by IgE antibodies
True or False: Allergies are diseases caused by an excessive immune response to foreign antigens and involve Type I and Type IV hypersensitivity.
True
True or False: Autoimmune diseases are caused by an excessive response to foreign antigens.
False; its a response to self antigens
True or False: IgE is an antibody produced by the body in response to allergens
True
True or False: The Fc receptor for IgE (FcεRI) is found on the surface of T-cells.
False; it is found on the surface of mast cells and basophils, as well as eosinophils
True or False: Allergens are typically large polysaccharide molecules with low solubility in body fluids.
False
True or False: Mast cells have FcεRI receptors on their surface that bind IgE, and when this IgE binds to an allergen, the mast cell releases granules containing histamine.
True
True or False: Anaphylaxis is a severe allergic reaction that can involve the restriction of the airway.
True
True or False: Individuals with atopic conditions typically have low IgE responses to allergens compared to normal individuals.
False
True or False: Delayed type hypersensitivity (DTH), or Type IV hypersensitivity, is primarily mediated by antibodies.
False; they are mediated by T-cells and macrophages
True or False: Allergen desensitization or immunotherapy aims to change the immune response to an allergen from a IgG response to an IgE response.
False; its the other way around
True or False: Histamine, released from mast cells, causes smooth muscle contractions and increased vascular permeability
True
True or False: Mucosal mast cells are predominantly found in vascularized connective tissue and skin.
False; it is mainly found in lungs and intestinal mucosa
True or False: Basophils do not express FcεRI receptors on their surface.
False
True or False: The cytokine IL-4 promotes the differentiation of Th1 cells.
False; they promote the differentiation of Th2 cells
Atopic allergic reaction
Driven by IgE, activates mast cells, basophils and eosinophils with FcεR
Non-atopic allergic reaction
Mast cells activated independently of IgE, by IgG, cytokines or complement
