Hypersensitivity Flashcards
What is Type I hypersensitivity mediated by?
IgE, mast cells and eosinophils
What is the reaction time for Type I hypersensitivity?
Minutes- it is very fast
Examples of Type I hypersensitivities
- Respiratory tract allergies (hay fever, asthma)
- Skin reactions (urticaria, hives, insect bites
- Gastrointestinal tract allergies (vomiting, diarrhea, shellfish, eggs)
What are the 4 events in Type I hypersensitivity?
- Sensitization phase
- Activation phase
- Immediate effector phase (mast cells)
- Late Effector Phase (eosinophils)
Describe the sensitization phase of type I hypersensitivity
Activation of Th2 cells help produce IgE, production of IL-4 and activates B lymphocytes and it generates memory
- Big picture: building up IgE level so that there is enough to activate mast cells
Describe the activation phase of Type I hypersensitivity
IgE will bind to high-affinity receptors and receptors cross-linked by allergens. IgE activates basophils and mast cells that are located in (gut lining, lung, nasal, conjunctiva, CT, and around BV)
Describe the immediate effector phase of Type I hypersensitivity
Activate the mast cells and basophils to produce an immediate reaction.
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What activates the mast cells?
Calcium influx
Activation of tyrosine kinase will do what?
Lead to production of cytokines and chemotactic factors and recruitment of neutrophils
Degranulation of mast cells will lead to what?
A release of histamine
Prostaglandins lead to
Vascular dilation
Leukotrienes lead to
Smooth muscle contraction
Cytokines (TNF) lead to
Inflammation (leukocyte recruitment)
Proteases lead to
Tissue damage
Vasoactive amines lead to
Vascular dilation, smooth muscle contraction
Intradermal challenge with allergens leads to what?
- Erythema
- Dilation of BVs = flare edema
- Swelling
- Release of serum into tissue = Wheal
What are common characteristics of anaphylactic shock?
- Dizziness
- Swelling of lips and tongue
- Swelling of larynx
- Wheezing and other asthmatic type difficulties
- Heart attacks and arrhythmias and severe drop in blood pressure
- Shock
- Nausea, vomiting, abdominal cramps
-Skin erruptions
Describe the late effector phase of type I hypersensitivites
- 6-24 hours with production of cytokines
- Mast cells produce eosinophils chemotactic factor that recruits eosinophils
- Reaction will persist for days
What do eosinophils release?
Cytokines and chemokines and ribonuclease (antiviral activity)
Describe how eosinophils have anti-parasitic activity
- Major Basic protein will destroy parasites
- Eosinophilic cationic protein can form ROS to destroy the worms
- Leukotrienes from mast cells cause smooth muscle contractions to expel the worms
What is the pharmacological intervention for anaphylaxis?
Epinephrine (Causes vascular smooth muscle contraction and increases cardiac output and relaxes the airway, it also inhibits the mast cell degranulation)
What is a pharmacological intervention for bronchial asthma?
Corticosteroids and leukotriene antagonists or phosphodiesterase inhibitiors
What do corticosteroids do?
Reduce inflammation
What do leukotriene antagonists do?
Relax bronchial smooth muscle and reduce inflammation
What do phosphodiesterase inhibitors do?
Relax bronchial smooth muscle
How does densisitzation work and what does it do?
Its repeated administration of low doses of allergens and works by possibly inhibiting IgE production and increasing production of other Ig isotypes
How do antihistamines work?
Block actions of histamine on vessels and smooth muscles
How does cromolyn work?
Inhibits mast cell degranulation
How does anti-IgE antibody work?
Neutralize and eliminate IgE
What is Type II hypersensitivity mediated by?
Soluble IgG and IgM antibodies
What are examples of Type II hypersensitivities?
Blood transfusion reaction where IgM will bind and hemolytic disease of the newborn (IgG)
What do environment carbohydrates induce the production of?
IgM in a T-independent manner
What is IgM good at?
Agglutination and activating the complement system- it will help destruct donor cells during transfucsions with the wrong blood type
What are the symtpoms of mismatched blood transfusions?
Fever, hypotension, nausea, vomiting, back and chest pain and RBC debris damages to the kidney
Hemolystic disease of the newborn is also known as
Erythroblastosis fetalis
What immunoglobulin passes the placenta to destroy RBCs of Rh+ fetus?
IgG
Hemolytic disease of the newborn symptoms include what?
Enlargement of the liver and spleen, and hemorrhages and elevated bilirubin
What test is used to determine whehter mother’s serum contains anti-RH antibody (IgG)?
Indirect Coombs test
How is the indirect Coombs test performed?
Mother’s serum is added to Rh-positive RBC, the RBCs are washed and then the Coombs Reagan is addedW
What is a prophylactic treatment for a mother who is Rh- having a Rh+ baby?
Rhogam, given after delivery to prevent sensitization
How does Rhogam work?
Removes fetal red cells before the mother can produce an immune response
How is Type III hypersensitivity mediated?
By antibody complexes
Why do antigen and IgG complexes form?
Due to persistent microbial infection or chronic exposure to extrinsic antigens (molds)
What do immune complexes activate?
The complement cascade
What does adhesion molecules expression increase?
Extravasation
What are macrophages and neutrophils activated to produce?
Cytokines (TNF and IL-1)
What are examples for Type III hypersensitivity?
Arthus reaction (localized) and serum sickness (systemic)
Why may arthus reactions present?
From repeated injection of antigens, high levels of antibodies present and they bind witht he introduced antigen and form complexes that activate complement
What is Type IV hypersensitivity mediated by?
Th1 cells (Delayed- Type Hypersensitivity)
How long does the reaction for Type IV hypersensitivity take?
24-28 hours after contact
What are the 3 types of DTH?
- Contact dermatitis
- Tuberculin Reactions
- Granulomatous Reactions
What can contact dermatitis be caused by?
Poison ivy, metals, chemicals, and infection with viruses
Describe posion ivy dermatitis activation
Pentadecacatechol on the dermis by skin contact. Activates a cutaneous reactiona nd antigen binds to host proteins, then the moleulce is presented by Langerhan’s cells and keratinocytes to Th1 cells. The activated Th1 cells produce cytokines and IFN gamma activate macrophages to produce tissue destructive enzymes and activate Th1 cells and then form the blister
What is tuberculin skin test used for?
Determining previous exposure to mycobacterium tuberculosis
Examples of granulomatous reactions
Tuberculosis, visceral leishmaniasis and hansen disease
Describe mechanism of tuberculosis
Macrophages infiltrate and ingest the bacteria, bacteria not digested and macrophages fuse with giant cells. The macrophages will recruit and activate Th1 cells and fibroblasts encase these cells to form a granuloma. Bacteria may die in the center, which is walled off, developing a cheesy center in the granuloma
What is leishmaniasis?
Parasite that lives inside macrophages. Development of the granuloma around the infected Kupffer cells in the liver
Hansen Disease (Leprosy)
Mycobacteria lepra is a very tough to destroy etiological agent
What are some novel therapies for hypersensitivity?
- Block costimulatory molecules CD28:CD80/86
- Block signal transduction
- Block cytokines and cytokine receptors (IL-1, IL-2, IL-17A, IL-12(p40), TNF, RNF receptor)
- Block adhesion molecules (integrins)
