Hypersensitivity Flashcards
What is a hypersensitivity?
Over reaction of the immune system to a harmless antigen (an antigen that most people don’t react to)
What is the distinguishing feature between the four types of hypersensitivity?
Whether the response is mediated by antibodies or cells
What are Type I immediate hypersensitivities more commonly called?
Allergies or atopic disorder
What immune molecule is responsible for Type I immediate hypersensitivities?
IgE
What does the severity of a Type I hypersensitivity depend on?
The route of entry taken by the antigen and the location of the responding cells
What makes someone genetically susceptible to having a type I immediate hypersensitivity?
High levels of IgE and eosinophils
What are the four main sources of allergens?
Inhaled materials, injected materials, ingested materials, contacted materials
What do all allergens have in common?
Low molecular weight, highly soluble particles, carried on proteins, contain peptides that can be presented to MHC Class II, effectively activate Th2
TH1 or TH2 are primarily responsible for type I immediate hypersensitivity?
TH2
What cytokine is responsible for stimulating IgE?
IL-4
How is the first exposure different from the second exposure for Type I hypersensitivities?
First: no reaction; get sensitization to the allergen; TH2 cells stimulate class switching on B cells to IgE which bind to receptors on mast cells Second: Crosslinking of IgE leads to degranulation of mast cells and get symptoms
What mechanism other than IgE crosslinking leads to degranulation of mast cells?
Crosslinking of IgG, C5a binding to complement receptors on mast cells
What is released from mast cells? How long after exposure do they show up?
Lipid mediators/vasoactive amines: leads to the immediate hypersensitivity reaction; minutes after exposure to Ag
Cytokines: leads to the late phase reaction; 2-4 hours after exposure to Ag
In a Type I hypersensitivity, how does the immediate phase differ from the late phase? What mediators are responsible for each?
Immediate: wheal and flare, from lipid mediators/vasoactive amines
Late: widespread inflammation, from cytokines
The wheal and flare are characteristic of which hypersensitivity? What causes the wheal and flare?
Type I immediate phase
Wheal- from leakage
Flare-from engorgement with RBC
What tissues are effected by lipid mediators? How are they effected?
Leaky vessels, bronchoconstriction, intestinal hypermotility, general inflammation
What were mast cells/eospinophils initially used for protection against?
Parasites
TNF leads to the expression of what when released from mast cells?
Adhesion molecules on endothelial cells
How are basophils/eosinophils activated?
By mast cell release
As the basophil population increases, what happens to the eosinophil population?
Decreases
During which part of the Type I hypersensitivity are eosinophils found?
Late phase
What are the main effects of eosinophils?
Promote chemotaxis, mucus production, and tissue repair
What is urticaria?
Localized swelling
What is angiodema?
Deep and diffuse swelling
What is the response to a subcutaneous allergen?
Second exposure leads to crosslinking of IgE causing mast cell degranulation and urticaria
When inhale an antigen, the antigen is presented to T cells leading to the secretion of which cytokine? (this cytokine is responsible for class switching to IgE)
IL-4
Upon second exposure, where will an inhaled Ag activate mast cells? What will be the result?
Mucosa- results in blood vessel permeability and recruitment of eosinophils which release mucus
What cytokine is responsible for allergic asthma? What type of hypersensitivity is allergic asthma considered?
IL-13; Type 1
What happens during an acute asthmatic reaction?
Mucosal mast cells capture Ag and degranulate; leads to bronchoconstriction, increased mucus production, and increased vascular permeability
What cells are responsible for chronic asthmatic reaction?
cytokines and eosinophil products
What is the difference between an acute asthmatic reaction and a chronic asthmatic reaction?
Acute: the allergen is present and leads to degranulation of mast cells
Chronic: a trigger (temp/cold/smoke) causes symptoms even though the allergen isn’t present
Ingestion of food allergens leads to diarrhea and vomiting; why does this happen?
Antigen can get into the blood stream and mast cell degranulation leads to smooth muscle contraction
What is the most severe Type I hypersensitivity?
Systemic anaphylaxis
What tissues can be effected by a systemic allergen?
Heart and vascular system, respiratory tract, GI tract
Why are systemic allergens life threatening?
Swelling in the heart leads to irregular heartbeat/ drop in BP/ reduced oxygen disseminaton
Bronchoconstriction of airways leads to difficulty breathing
GI smooth muscle contracts: get vomiting and diarrhea
How are systemic allergen responses treated?
Epinephrine
What is the difference between an ingested allergen and a systemic allergen in terms of location of the mast cells?
Ingested: mast cells are in the mucosa and then the antigen can enter the bloodstream
Systemic: antigen is in the bloodstream and then enters tissues to activate mast cells all over the body
Why do allergies tend to run in families?
There are certain genes that are associated with allergies
If someone has more IL-4 will they be more or less susceptible to allergies?
More susceptible
Developed countries have a higher incidence of allergies than poorer countries where still have exposure to parasites. What is considered protective against allergic responses?
A balance between TH1 and TH2 with a slight favoring for TH1
If someone has a low genetic susceptibility to allergies and living in an unhygenic environment, will their immune system be pushed towards a TH1 or TH2 response?
TH1
What are some potential treatments for Type I hypersensitivities?
Avoid allergen, treat symptoms (anti-histamines, corticosteroids, aluterol, epinephrine), try desensitization, block cytokines
How does desensitization work?
Expose to small amounts of antigen to try and get more IgA and IgG Ab which then block the binding of Ag from binding to IgE on mast cells
What types of hypersensitivties are important for autoimmunity diseases?
Types 2, 3, 4
What immune molecule mediates Type II?
IgG and complement
How can penicillin lead to a type II hypersensitivity?
Alters the proteins on RBC so that they look foreign; IgG binds and binds complement resulting in lysis of the RBC
Why are we only tolerized to our own blood antigens?
Blood antigens are similar to bacterial antigens so don’t want to limit are immune response and the ability
Which blood type is the universal donor?
O
Which blood type is the universal recipient?
AB
Which immune cells are responsible for Type III hypersensitivities?
Large Ag:Ab complexes that can’t be cleared by complement
Why are Ag:Ab complexes a problem?
Deposited systemically and can result in tissue damage
When Ag:Ab complexes are deposited in the blood vessel walls, renal glomeruli, and joint spaces, what types of disease result? How do the reactions that induce these reactions get into the body?
Vasculitis, Nephritis, Arthritis;
Intravenously
What disease occurs when Ag:Ab complexes are deposited in the perivascular area?
Arthus reaction
What disease occurs when Ag:Ab complexes are deposited in the capillary/alveolar interface?
Farmer’s lung
In Type III reactions, how are mast cells degranulated?
Ab:Ag complexes stimulate C5a to bind to mast cells or bind directly to Mast cells by FcyRIII on mast cell
If a tetanus booster is given within 5 years of the previous booster, which hypersensitivity results? Why?
Type III- because already have high levels of these antibodies
What type of hypersensitivity is associated with serum sickness? How long does it take for the symptoms to arise?
Type III; take approximately a week because need to get antibodies
What are the symptoms of serum sickness?
Fever, vasculitis, arthritis, nephritis
What immune component mediates Type IV hypersensitivity?
T cells
What are the three different “syndromes” that result from Type IV hypersensitivities?
Delayed, contact, gluten sensitive enteropathy
Type IV require more or less antigen exposure than the other hypersensitivities?
More
What T cell population is involved in a delayed type hypersensitivity? What do these cells do that lead to inflammation?
TH1- release cytokines that recruit macrophages, increase vascular permeability
With contact hypersensitivity what immune cells are responsible? What do they do?
TH lead to the activation of more cells, TC cells kill cells that are presenting the antigen
What chemokine can increase the expression of MHC class II and therefore increase the Type IV reaction?
IFN-gamma
