Hypersensitivity (Lecture 5) Flashcards
Hypersensitivity (definition)
A normal, but exaggerated/uncontrolled immune response to an antigen that can produce inflammation, cell destruction, or tissue injury
Immediate Hypersensitivity
Antibody Mediated. Minutes to Hours.
Delayed Hypersensitivity
Cell Mediated. Days or longer.
Immunization/Sensitization
An immunologic reaction dependent on the host’s response to a subsequent exposure to antigen.
Small quantities of antigen may favor sensitization by:
restricting the quantity of antibody formed
Allergic/Hypersensitive reaction may follow:
Second exposure to antigen. It reveals the existence of sensitization.
Most significant property of IgE antibodies
Can be specific for hundreds of different antigens (animal dander, pollens, food, molds, dust, metals, drugs, insect stings)
Allergy vs. Atopy
Originally Allergy meant any altered rxn to external substances
Originally Atopy referred to immediate hypersensitivity mediated by IgE antibodies
USED INTERCHANGEABLY
Allergen (definition)
Antigens that trigger allergic reactions
Allergen (properties)
Low molecular weight substances, can be inhaled, eaten, or administered as drugs
Different types of antigens can cause
Hypersensitivity
Latex - What is it? Where is it found?
Protein in the sap of Brazillian rubber tree
“natural rubbber products” made from sap. Disposable gloves, condoms, diaphragms.
Latex Allergies/reactions can be caused by?
Direct contact with latex
Inhaling airborne latex fibers
NOT synthetic latex
Frequency of latex allergies?
Rare, <1% of US population has a latex sensitivity
3 types natural latex reactions
- IgE mediated allergic rxns (Type I hypersensitivity)
- Cell-mediated contact dermatitis (Type IV hypersensitivity)
- Irritant dermatitis
What is Irritant Contact Dermatitis?
Reaction, not an allergy. Appears where latex has touched the skin. May be a warning sign that latex allergy may develop.
Irritant Contact Dermatitis symptoms
Swelling, redness, itching after latex exposures
Environmental Substances (definition/description)
Substances in the form of small molecules that can trigger reactions
Small molecules can diffuse into skin and act as haptens (delayed hypersensitivity with contact dermatitis)
Environmental Substances - Dust
Enters respiratory tract.
Mimics parasites.
Can stimulate antibodes (Immediate IgE, causing rhinitis or asthma; or IgG, can cause farmer lung)
Environmental Substances - Drugs
Administered orally, by injection, or on the skin
Hypersensitivity response mediated by IgE, IgG or T lymphs
Environmental Substances - Metals, Chemicals
Especially nickel. Can cause Type I rxn.
Haptens. Bind to body proteins or MHC, which is regonized by T cells, initiating a reaction
Infectious Agents that Cause Hypersensitivity Rxns
Influenza (damage respiratory epithelial cells, cytokine storm)
Streptococci (immune complex disease)
Self Antigens
Reactions to self antigens normal in small amounts
Can become hypersensitivity if exaggerated
Food Allergies - Rates in Children & Adults
5% kids under 5 y.o.
4% teens and adults
Some allergies are “grown out of”, leading to decrease between ages (commonly wheat, milk, egg, soy)
Overall prevalence increasing
What Ig mediates most Food Allergy rxns? What foods cause most of these rxns?
IgE
Cow’s milk, soy, chicken eggs, peanuts, tree nuts, wheat, fish, crustaceans
Cell-Mediated reactions are most commonly caused by
Soy, wheata, rice, oats, cow’s milk
Are food allergies and intolerance the same thing?
No
Foods with proteins similar to the rubber tree (& those that cause progressive symptoms)
Nuts, fruits
Figs, apples, carrots, celery, melons, potatoes, papayas, pitted fruits
Foods with proteins similar to rubber tree are at risk of/can cause:
At risk of developing a latex allergy.
Can cause anaphylactic reactions in latex sensitive people
NIAID Guidelines
National Institute of Allergy and Infectious Diseases
IgE-mediated reactions to food (food allergies)
Non-IgE-mediated rxns to certain foods (e.g. celiac disease)
Mixed IgE & non-IgE disorders
NIAID ood Allergy Reactions & Treatments
Can cause severe allergic reactions, anaphylaxis, death
No treatment, only allergen avoidence
Types of Hypersensitivity Reactions & General Characteristics
Defined by the principal mechanisms responsible for a specific cell or tissue injury that occurs during an immune response.
Types I, II, III - antibody mediated
Type IV - cell-mediated
Type I Anaphylactic Rxns
Can range from mild to life-threatening anaphylactic reactions. Anaphylactic is not Anaphylaxis/Anaphylactic Shock.
Type I - Etiology
Atopic allergies (source not always known)
Drugs (systemic penicillin)
Insect stings (hornets, yellow jackets)
Immune-mediated IgE adverse food rxns
Type I - Immunologic Activity
Mast cells (cellular receptors for IgE, granules contain complex of heparin, histamine & zinc ions. Released when allergen interacts with membrane-bound IgE)
Immediate hypersensitivity - basis of acute allergic reactions
Type I - Mast Cell Degranulation
The mast cell carries high-affinity receptors for the Fc portion of IgE. Allergen-specific IgE, occupying these receptors, induces mast cell degranulation
Type I - Basophil Granules & Cytokines
IL-3 stimulated basophils to form & release histamine, IL-4, IL-13, leukotriene C4 (major mediators of allergy and asthma)
Basophil granulocytes considered key effector cells in Th2 cell immune responses and allergic inflammation
Type I - Anaphylactic Rxn (definition)
The clinical response to immunologic formation and fixation between a specific antigen and tissue-fixing antibody. Usually mediated by IgE
Type I - Anaphylactic Rxn (stages)
- Antigen attached to basophil/mast cell membrane IgE. Crosslinking two IgE necessary to initiate stage 2.
- activated mast cells and basophils release various mediators
- the effects of mediator release produce vascular changes and activation of platelets, eosinophils, neutrophils, and coagulation cascade
Type I - Anaphlyactoid Reaction
Anaphylaxis-like (clinically similar)
NOT Antigen-Antibody mediated
Immunologically inert materials that activate serum and tissue proteases and the alternative pathway of the complement system
Offending substances act directly on mast cells (causing release of mediators) or on tissues (eg C3a, C5)
Type I - Atopic reaction
Exaggerated response to allergens
Characterized by the production of allergen-specific IgE antibodies, and positive rxns to extracts of common airborne allergens with skin prick test
T cells respond to allergens by inducing cytokines produced by Th2 cells (IL-5, IL-13) rather than by Th1 cells
Hallmark of allergic disease is the infiltration of affected tissue by Th2 cells
Type I - Atopy Signs and Symptoms (localized reaction)
Single does of common airborne allergen can cause skin redness, sneezing, wheezing, within minutes
Immediate hypersensitivity rxn, followed by a late-phase reaction that peaks 6-9 hours after exposure, then subsides (depends on amount of allergen)
Localized reaction - immediate response to mediators release from mast cell degeneration. Urticaria, angioedema at site of exposure. Bowel if ingested. Severe but rarely fatal
Type I - Atopy Signs & Symptoms (Generalized/Anaphylactic Reaction)
Dramatic, rapid onset
Produced by mediators from mast cells (cytokines, histamine)
Histamine release leads to constriction of bronchial smooth muscle, edema of trachea & larynx, stimulation of smooth muscle in GI tract
Antihistamines have no effect
Type I - Atopic, Allergic Disease in Children
Allergy march
Formation of IgE in early life, sensitization to food allergen can manifest as colic or chronic otitis
Risk factors:
-family history for allergy
-sensitization to food allergens
-total serum IgE > 100kU/L before age 6
-living in allergen rich environment
-smoking
Type I - Testing
Patient History
Lab tests to ID foods
Skin (pin prick) test
Patch testing if non-IgE food allergy suspected
Food-specific serum IgE testing
Serum tryptase, an enzyme released with histamine, if they have been activated in an anaphylactic reaction
Type I - Skin Test Protocols
ID foods that may provoke IgE-mediated, food induced allergic reactions
Skin Puncture Test (SPT)
-scatches/needle pricks & drop of possible allergen solution
-simple outpatient
-NOT for children, pregnant women
-risk of triggering anaphylactic rxn, initiating new sensitivity
Patch Testing
- evaluation of contact food allergies, detection of contact dermatitis
- patch that has been soaked in the allergen is taped to skin for 24-72 hours
Type I - Laboratory Evaluations
In vitro testing lacks risk of systemic reaction & doesn’t depend on skin reactivity
Serum allergen-specific IgE (sIgE) clinically significant
Quantitative determination of serum IgE antibodies necessary for differential diagnosis & for ID of allergens
Type I - ImmunoCap (Lab Eval)
In vitro quantitative measurement of IgE in human serum
Tests for 650+ allergens, 70+ allergen components
Consider patient’s age, symptoms, home environment (pets, hobbies), residence location
Type I - Chemiluminescent enzyme immunoassay (Lab Eval)
Third generation sIgE
Solid-phase (bead), two-step chemiluminescent enzyme immunoassay (EIA)
Allergens covalently lines to a soluble polymer-ligand matrix. Allows immunochemical rxns to occur in liquid phase for random access automation
Type I - Treatment (big picture)
ID and eliminate allergens
Drug Therapy
Desensitization
Type I - Drug Therapy Treatment
Epinephrine (adrenaline): immediate lifesaver
Antihistamines: act much slower, not useful in asthma. for allergies affecting skin, nose & mucous membranes
Specific receptor antagonists: block leukotrienes
Corticosteroids: topical, preventative
Other drugs: aim to block Th2 cytokine pathway or prevent IgE binding
Type I - Desensitization Treatment
Immunotherapy
Improve allergy symptoms caused by SPECIFIC allergens
Associated with:
-downregulation of the sytokines produced by the Th2 cells
-upregulation of cytokines produced by Th1 cells
-induction of Treg cells
Type II Hypersensitivity Reactions
Initiated by IgE-Antigen interaction
Target is fixed in the tissues, or on cell surface
3 mechanisms:
- Antibody-dependent, complement-mediated cytotoxic reactions (type 1)
- Antibody-dependent, complement-mediated cytotoxicity (type 2)
- Antireceptor antibodies
Type II - Antibody-dependent, complement-mediated cytotoxic reactions (type 1)
IgG or IgM interaction with cell-bound antigen
Binding activates complement and destruction of the cell (cytolysis) to which antigen is bound
RBC, WBC & platelets can be lysed
Ex: immediate transfusion rxns, immune hemolytic anemia
Type II - Antibody-dependent, complement-mediated cytotoxicity (type 2)
Depends on initial binding of specific Abs to target cell surface Ag
Ab coated cells lysed (by NK, macros) expressing Fc receptors
Fc recepetors on NK/macros attach to Fc portion of antibody coating the target cell
