3.2.12 - Hypersensitivity Flashcards
What are the 4 types of hypersensitivity reactions?
Anaphylactic (type I)
Cytotoxic (type II)
Immune complex disease (type III)
Cell-mediated delayed hypersensitivity (type IV)
Antibody class involved w/ anaphylactic reaction
IgE
IgE half life
2-3 days
IL-___ is important for class switching to IgE and IL-___ plays a role
IL-4
IL-13
Where there’s less parasitic infections, there’s an increase/decrease of atopic allergic reactions
Increase
Antigens are also referred to as
allergens
3 common sources of allergens
Inhaled, injected, ingested
Steps for IgE attaching to mast cells and basophils
- Allergen enters across mucosal membrane
- Cytotropic antibody (IgE) attaches to mast
cell by Fc receptor
Fab (antigen binding site)part’s ready
to interact w/ allergen - IgE remained attached for months on surface
of mast cell, basophil, and activated
eosinophils
3 features of inhaled allergens that promote priming of the Th2 cells that drive the IgE response
Molecular type
low dose
high solubility
IgE only remains isolated in blood for ___, but can remain attached to leukocytes for ___
few days
months
Primary sensitization steps for anaphylactic reaction
- exposure to pollen
- extraction of antigen goes to mucosal surface
- activation of Th2 cells
- production of IgE and binding to mast cells
IgE receptor
FcER1
what else can interact w/ mast cells and cause release of mediators?
Anaphylatoxins (mainly C3a and C5a)
What happens during the 2nd exposure to an allergen?
Mast cell coated in IgE antibody and allergen interacts w/ it and causes mediator release
Results in
Immediate hypersensitivity rxn within minutes (found in granules) AND late phase rxn within 2-8 hours (produced by mast cell in membrane)
3 important mediators released by mast cells. What do each of them do?
Histamine
- capillary dilation
- increase vascular permeability
- Increase in mucous secretions
ECF-A
Leukotrienes
- similar properties to histamine
The peak expiratory phase in response to inhaled allergen lasts for ___ min. The immediate response is due to ___ and the late response is due to ___
less than 30 min
Histamine
Leukotrine
What are the 2 types of mast cells? Describe
Connective tissue - associated w/ blood
Mucosal - mucosal mast cells
Mast cell’s release granules into what 3 locations? What is the effect in each of these?
GI tract
- diarrhea and vomiting
Airways
- expulsion of airway contents
Blood vessels
- Increased lymph flow
What are the 2 types of allergic manifestations? What are examples of each? Which one has a genetic predisposition?
Atopic or local anaphylaxis
-ex: allergic rhinitis (hay fever)
- genetic predisposition
Systemic anaphylaxis
- ex: anaphylactic shock
Acute vs. chronic response steps in asthma
acute
- Mucosal mast cell captures antigen → antibody response by producing IgE → inflammation causes SM to contract, increase in mucus secretion, increase in blood vessel permeability
- Cytokines produced bring in eosinophils
—Eosinophils can release their toxic substances
chronic
- Mediated by cytokines and eosinophil products
systemic anaphylaxis results from ___. What is the local and systemic treatment?
systemic release of histamine and leukotrienes
- occurs in minutes
local = antihistamine
systemic = epinephrine
Describe skin testing. Immediate response is due to ___ and response ~30 min is due to ___
Use to test allergies
Look for wheel (swelling) and flare (reddening around swelling)
leukotrienes
Histamine
Describe hypo-sensitive treatment. You can also use a ___ antibody
- If you already know what you’re allergic to
- Treatment plan that gives you small amount of what you’re allergic to, but not enough to cause a response, only a small immune response
- IgE antibody starts to decrease over time
- IgG (blocking antibody) is produced over time in tissue fluid that has a chance to interact w/ allergen causing a problem before it can interact w/ IgE on mast cell
anti-IgE monoclonal antibody
4 types of IgE mediated allergic reactions
Systemic anaphylaxis
Wheal and flare
allergic rhinitis
bronchial asthma
Describe cytotoxic (type II) reaction
Antibody is directed against antigen on surface of cell
End result = cell lysis through complement activation
Examples of cytotoxic reaction
blood transfusion reaction
drug reactions
autoimmune hemolytic anemia
antibody-dependent cell cytotoxicity (ADCC)
Describe autoimmune hemolytic anemia
- occurs in cytotoxic reactions
- Penicillin can either bind to bacterial transpeptidase and inactivate it OR can modify proteins on human RBC to create foreign epitopes (develops antibody against penicillin)
—End result can be hemolytic anemia
Some drugs are ___ that can interact w/ surface proteins of cells and induce an antibody response
Haptens
- don’t initiate immune response by themselves but if they react w/ decreased surface proteins they can trigger response
Example of antibody-dependent cell cytotoxicity (ADCC)
Patient response to therapy directed against B cells employing an anti-CD20 antibody Rituximab → CD20 found on B cells as is CD19
- NK cell has receptor that binds to IgG antibody which causes NK to release (perforin and granzymes)
- Retuximab is front line therapy in treating patients w/ B cell lymphomas
Immune complex disease (type III) reaction is initiated by ___. Which can activate ___
antigen-antibody complexes which can induce an inflammatory response
Complement system
Example of a local response in immune complex disease. It’s ___ induced. It results from and what causes it? Site of reaction?
Arthus reaction
Locally
previous exposure to antigen
vaccine
skin
What are the 2 responses in immune complex disease?
Local and systemic response
time of reaction for arthus reaction
5-6 hours after injection of antigen
Describe systemic reaction in immune complex disease
Antigen-antibody complexes circulate throughout bloodstream and settling in organs, like the kidney, and initiation inflammatory response
What do neutrophils try to do in the systemic reaction in the immune complex disease?
Neutrophils try to remove antigen-antibody complexes and destroy filtration system of kidney → renal failure if it goes on for too long
If you have a large dose of drug that’s not cleared right away, you have the ability to make ___, that then over time form ___
antibody
antigen:antibody complexes
autoimmune disease has continued production of
antigen:antibody complex
