Hypersensitivity/ Allergy Flashcards
State of heightened reactivity to antigen
Hypersensitivity
immune responses to innocuous antigens that lead to symptomatic reactions upon re-exposure
hypersensitivity reactions
damage to host tissue caused by hypersensitivity reactions to typically innocuous antigens
hypersensitivity disease
Involves IgE-dependent triggering of mast cells
Immediate Type/ Type I hypersensitivity
Commonly referred to as allergy
Immediate Type/ Type I
Involves IgG antibody that is reactive with cell-surface or matrix antigens
Type II: Altered Self
involves production of antigen:antibody complexes
type III: Immune complex
altered host hypersensitivity
Type II: altered self
immune complex hypersensitivity
type III: Immune complex
T cell mediated hypersensitivity
Type IV: Delayed type
delayed type hypersensitivity
Type IV: Delayed Type
Antigens that elicit a Type I hypersens. response are called
allergens–> slectively stimulate Th2 cells that can drive class switching from IgM to IgE (weakly opsonizing/low dose/extracellular)
Main cell type involved in type I hypersensitivity upon first encounter with the antigen
Th2 CD4+–> b/c it can promote class switiching to IgE which is taken up by the high affinity IgE receptor on mast cells etc…
Type I hypersensntitivity MOA
Antigen selectively stimulates a TH2 response that drives class switiching to IgE specific for the encountered antigen
- ->then mast cells take up the IgE ab’s on their FCgammaR1 (high affinity IgE receptor)–>second exposure to Antigen–> massive degranulation of MAST CELLS
- TH2 driven IgE responses
Common features of most allergens
- Small
- Highly Soluble
- Carried on Dessicated particles (stable)
- diffuse into the mucosa from the particles
High or Low dose exposure for allergens?
Low Dose ( will cause Th0 to become a TH2)
Th2 release which cytokines
3 4 5 10 13 TGF beta
Many common allergens have______
enzymatic activity
IgE is important in the immune response to _____
parasites
(They produce proteases that aid in the parasites own movement through the host’s tissue–>therefore, IgE response to protein allergens is largely physiologic–> but becomes pathologic in response to innoccuous environmental allergens
protein (enzymatic*) allergen +TH0–> TH2–>promotes class switching in Naive B lymphocytes to IgE specific to that protein
know that
One of the pre-requisites for Type I hypersensitivity is that the initial response must be….
IgE response
How does class switiching to IgE occur
TCR of an Effector CD4 TH2 t cell becomes ligated (by specific peptide antigen presented on MHC II molecules) on the B cell (an antigen presenting cell)–> TH2 secretes IL-4, 5, and 13–> mediates class switching to IgE
All the cells hat can INITIATE Type I Hypersensitivity reaction
Mast Cells (primary)
Eosinophils
Basophils
–>all of these have the high affinity IgE FC receptor
Cross-Linking of IgE receptors on a mast cell, basophil and eosinophil leads to what?
degranulation of granules that contain mainly histamine…Leukotriens, Prostaglandins, TNF, Cytokines, PAF and neutral proteases
What does atopic mean
predisposed to IgE allergens
Is there a genetic basis to atopy
yes 40% of Caucasian population
Chromosomes involved in genetic basis for atopy
11–> high affinity IgE receptor
5–>IL 3 4 5 9 13 and GM-CSF (isotype swithcing and mast cell survival)
First step of response to allergens in skin test
Wheal and Flare response
What happens in a Wheal and Flare Response
Mast cell degranulation–>releases histamine–> increased permeability–> edema (Wheal)
increased blood flow (flare)
2nd step in response to allergen skin test
6-8 hours after injection (late phase reaction)second reaction at the site of injection
*wiki says primarily cytokine mediated
The effects of IgE mediated allergic reactions vary with_____
site of mast cell activation
*only those cells at the site of action will cross-link and be degranulated
Major sites of allergen-Mast cell response
mucosa of the respiratory tract, GI tract
Insect bite allergens gain access to?
connective tissues and blood
Body responses (coughing, diarrhea) to allergens are a response to
expel “parasites” from the body
Systemic anaphylaxis
allergens in the blood
*widespread activation of mast cell degranulation causing both an increase in vascular permeability and widespread constriction of smoothe muscle
Fluid leaving the blood in response to allergens in the blood–>
Low Blood pressure and anaphylactic shock
Reactions that resemble anaphylactic responses but do not involved IgE and allergen
Anaphalactoid
tx. for anaphylactic and anaphalactoid
epinephrine-> stiimulates reformation of tight junction between endothelial cells-> reduces blood vessel permeability->repletes blood volume–>diminishes swelling and rapidly restores blood pressure
Rhinitis and Asthma are caused by_____
inhaled allergen
mild allergic response characterized by violent bursts of sneezing and runny now in response to inhaled allergens
allergic rhinitis
- allergens that diffuse across the mucous membranes of nasal passages and activate mucosal mast cells
- release of mucous rich in eosinophils
Allergic Rhinitis can extend to
ear and throat–> leading to accumulation of fluid in Eustachian Tubes (bacterial infections)
Disease causing CHRONIC breathing difficulties
Allergic Asthma
although wiki says it is the RESULT of chronic inflammation
Triggered when submucosal mast cells in LOWER respiratory tract are stimulated by allergen/IgE interaction
allergic asthma
Pulmonary findings in allergic asthma
- increase in fluid and mucours into respiratory tract
- bronchial CONSTRICTION do to contraction of bronchial smooth muscles
- chronic asthma related inflammation can result in persistent infiltration of TH@’s, eosinophils, neutrophils)
overall effect of asthma
trapping of air in lungs making breathing more difficult–> can be fatal
Chronic asthma can be considered
Type IV hypersensitivity (antigen independent)–> excacerbated by immune response to bacterial or viral infections of respiratory tract (infections that elicit Th2 cells)
hives=
urticaria ( caused by release of histamine by mast cells IN THE SKIN)
*essentially a wheal and flare reaction
angioedmea
inflammation caused by mast cells IN THE SUBCUTANEOUS TISSUE)
*SWELLING IS MORE DIFFUSE THAN URTICARIA
FOOD ALLERGEN MOA
allergen passes through wall of gut and binds to IgE receptors on mast cells–> accumulation of fluid in the gut
- diarrhea, cramps, vomiting all caused by smooth muscle contraction
- can have hives and angioedema too
Therapy for PREVENTION of allergic reaction
- modify pt.’s behavior
- pharmacologic: give drugs that reduce the impact of contact with allergen
- prevent production of allergen specific IgE
* desensitization: a series of shots of increasing allergen doses that gradually changed the Th2 IgE response to a Th1 response in which no IgE is produced
Type of Hypersensitivity induced by antibodies specific for alterd components of Human Cells
Type II
Most common examples of Type II
hemolytic anemia and thrombocytopenia following drugs administration
common drugs that cause Type II
penicllin (most common)
quinidine
methyldopa
Penicillin allergy MOA
- new epitopes are generated by the drug binding to RBC’s
- Penicillin Bound RBC’s are also coated with compliment (a inevitability given that there is an infection going on you are treating)
- Phagocytosis by macrophages
- Phagocytes present “new” epitopes to T cells–> Th2 phenotype effector is the product
- Th2 interacts with B cell–> IgG for altered host RBC is the outcome
- IgG binds to RBC’s and initiation MAC–> hemolysis (anemia)
Immune complex hypersensitivity
Type III
Small or Large Immune complexes are the trouble with Type III
Small–> inneficient compliment activation–>not taken up by macrophages properly and
*they remain in circulation and get deposited along blood vessels
Type III once immune compexes get depositied onto vessel wall–>
tissue damage when sufficient number of immune complexes aggregate
*circulating leukocytes recognize immune compxe aggregates via Fc and compliment receptors and are activated to promote INFLAMMATION
Type III EXPERIMENTAL TEST that takes place under the SKIN
Arthus reaction
Serum sickness
immune responses to non-self material administered into the blood stream as a tx. for a variety of illnesses
*caused by systemic circulation of immune complexes–> eventually a systemic inflammatory response
Serum sickness presents as
fever, chills, glomerulonephritis, rash, arthritis
Farmer’s lung
Continual inhlation of dust and mold spores that occurs over a long period of time–> body makes and IgG mediated response (not IgE) and the resultant inflammation caused by immune complex build up in the lungs causes respiratory dysfunction
Bird breeders lung
Type II hypersensitivity to avian antigens
Hypersensitivity mediated by antigen specific t cells
Delayed Type Hypersensitivity
time frame of DTH
1-3 days
time frame for immediate type hypersensitivities
within minutes
DTH require_____ quantities of antigen
100-1000 fold larger due to inefficient antigen processing and presentation
common DTH antigens
poison ivy
nickel
insect venom
mycobacterial proteins
positive TB test will show
inflammation around the site 24-72 hours after test
*Cytokines here are produced by Th1 cells that were activated by resident macrophages
lipid-like molecule responsible for poison ivy
pentadecacatechol
What happens on initial poison ivy interaction
poison covalently interacts with host tissues after penetrating skin and forms NEW antigens–> these are recognized as NON SELF
>local APC’s take up this antigen and present it to naive cells which
>formation of an effecto CD4 t cell army
VERY LITTLE INFLAMMATION RESPONSE
CTL’S CAN BE ACTIVATED DIRECTLY BY APC’S AS WELL
SECOND POISON IVY RESPONSE
> ANTIGEN SPECIFIC CTL’S AND ANTIGEN SPECIFIC TH1 CELLS (DESTROY TISSUE WITH PENTADECACATECHOL)
AND
TH1’S THAT ACTIVATE MACROPHAGES AND PRODUCE INFLAMMATION
EXAMPLE OF CONTRACTILE SENSITIVITY
poison ivy and nickel
*contact with the allergen is required to initiate the allergic response
