Module 8 Allergy Flashcards
What are the 4 types of hypersensitivity reactions?
Different effector mechanisms underlie the four types of hypersensitivity reaction:
- Type I hypersensitivity reaction / Immediate hypersensitivity: triggered by the interaction of an allergen with allergen specific IgE bound to FcERI of mast cells, basophils and eosinophils.
Example: inhalation of particulate antigens such as plant pollens
- Type II hypersensitivity reaction: caused by an IgG response to small, chemically reactive molecules that become covalently bonded to components of the outside surface of human cells. The chemical reaction modifies the structure of these components, creating new cell surface epitopes, which are then perceived as foreign antigens.
Example: penicillin
- Type III hypersensitivity reaction: caused by small immune complex of antigen and IgG that deposit in the walls of a blood capillaries, lung alveoli and kidney glomeruli.
Example: when antibodies or other proteins derived from nonhuman animals are given to patients, Type III hypersensitivity reactions are a potential side effect
- Type IV hypersensitivity reaction / delayed-type hypersensitivity (reactions happened 1-3 days after exposure): only one that is not mediated by antibodies. It is mediated by antigen-specific T cells.
Examples: Metal / poison ivy contact sensitivity
How does Th2 cells mediate the immune responses to defend against parasite?
Type 1 immunity mediated by Th1 cells does not work against parasites due to their large size and cannot be ingested by phagocytes.
Immunity mediated by Th2 cells called type II immunity: Th2 —> helps B cell switch type to make IgE —> IgE then binds to Fc receptors of Basophils, Mast cells and eosinophils (arming of these cells) —> across link the effector cells with different antigens of the parasites —> cells degranulates and eject the parasites from their human host
Important cytokines: IL-13 secreted by Th2 cells and influences the dynamics of the intestinal epithelium
IL-22, secreted by endothelial cells and includes DC —> travel to draining lymph node and stimulate antigen-specific T cells to differentiate to CD4 Th2 cells
The Hygiene Hypothesis
What cell initiate Th2 response
Basophils.
TGF-beta and IL-3 promote the maturation of basophils while suppressing that of eosinophils
Basophils is very scarce and only constitutes 1% of white blood cells
Step 1: Goes to secondary lymphoid tissues, where they secrete IL4 and IL13 —> these cytokines polarized T cells to make Th2 response —> Basophils also has CD40L and binds to CD40 of B cells —> drives isotype switching to IgG3 or IgE —> IgE bounds to FcRi on basophils and now the basophils is memory cell (because it has antigen specific receptor and can active basophils in a secondary response to the same pathogen)
The sequence of antibody secretion
IgM —> IgG 3
IgM —> IgE (very low affinity) —> IgG3–> IgG1–> IgG2–> IgG4
IgG4 is last to be made. IgG4 cannot fix complement and is preferentially bound by inhibitory receptor FcrRIIB.
IgG4 can exchange one heavy chain and its associated light chain with those of another IgG4 antibody of a different specificity and thus acquire two different antigen specificities. It can bind tightly to an antigen with just one Fab
How does IgG4 shut down inflammatory response and limiting tissue damage?
What are some of the distinctive features of IgE
IgE: does not recirculate in the blood and lymph, but is taken up and concentrated in the tissues, where it irreversibly binds to FcERI on mast cells
Features of IgE and FcERI complex
IgE and FcERI arm each mast cell with a high diversity of antigen-specific receptors
Mast cells express about half a million copies of FcERI which gives each mast cell the capacity to bind IgE representing thousands of different antigenic specificities
Mast cells are long-lived cells that are resistance to apoptosis and other mechanisms of cell death. They are also an extreme form of memory cell, because everyone of the IgE molecules present on its surface is there as a result of a past infection. Thus, each mast cell remembers numerous infections
What are the Mast cells function and cytokines?
Mast cells express TLR and Fc receptors for IgA and IgG and contribute to innate and adaptive immunity
Histamine receptors
There are three histamine receptors — H1, H2, and H3
Histamine binding H1 on smooth muscle cells and endothelial cells of blood vessels —> Increases the permeability of the endothelium —> other inflammatory mediators getting access to the allergen-containing tissue
TNF-alpha
Histamine and TNF-alpha are complementary: TNF-alpha activates endothelial cells and increase their expression of adhesion molecules and causing increased migration of leukocytes out of the blood and into the inflamed tissue
Characteristics of Eosinophils
- Mostly tissue resident and particularly the connective tissue
- Granules loaded with arginine-rich basic protein
How does a person get sensitized to inhaled allergen?
Genetic variation associated with susceptibility to asthma
Two allergic reaction phases
- Immediate reaction: wheal-and-flare (release of histamine and other mediators)
- Late-phase reaction: (caused by the leukotrienes, chemokines, and cytokines released by the mast cells after IgE-mediated activation)
The effects of IgE-mediated allergic reactions vary with the site of mast-cell activation
What causes systemic anaphylaxis
Caused by allergens in the blood
Chronic asthma
In chronic asthma, the airways can decode almost completely occluded by plugs of mucus.
A generalized hyper responsiveness or hyperactivity in the airways also develops.
it is a type IV hypersensitivity reaction caused by effector T cells
Urticaria
Allergens that activate mast cells in the skin to release histamine cause raised itchy swellings called urticaria / hives
