Hypersensitivity 2 (RVSP) Flashcards
Enzyme allergen from the fecal pellets of the dust mite
Der P1
Scientific name of the common dust mite
Dermatophagoides pteronyssinus
Broken down by Der P1 that enables it to cross the mucosa
Occludin of the tight junction
Interleukins (ILs) for development of mast cells
IL-4
IL-9
ILs For development of eosinophils
IL-5
IL-9
ILs for differentiation of B cells
IL-4
IL-13
ILs to stimulate the overproduction of mucus
IL-4, 7, 9, 13
Term for the genetic trait to have a predisposition for localized anaphylaxis
Atopy
What do atopic individuals have higher levels of?
Higher levels of IgE and eosinophils
Mechanism of allergic response; attachment of IgE to Mast cells
Sensitization
Receptor of mast cells for IgE
Fc receptor
Effect of sensitization to IgE
Increase of IgE life span
Half-life of IgE in serum
2-3 days (sometimes up to 10)
When attached to the FceR (Fc epsilon Receptor), the half-life of IgE is increased to
Months
Cells that have high affinity for IgE
or
Cells that have high affinity IgE receptor
Mast cells
Basophils
Activated eosinophils
Triggers release of granules from cell (Type 1 hypersensitivity)
ALLERGEN binding to IgE attached to FcER
Condition of mast cells during secondary exposure to allergen
Mast cells are already primed with IgE on surface
During secondary exposure to allergen, the allergen binds IgE and cross-links to activate signal with ______________, ______________, ______________, and ______________
- Tyrosine phosphorylation
- Ca2+ influx
- Degranulation
- Release of mediators
Primary mediators in Type 1 H
- Histamine
- Cytokines (TNF-a, IL-1, IL-6)
- Chemoattractants for neutrophils and eosinophils (NCF-A, ECF-A)
- Enzymes (tryptase, chymase, cathepsin)
Secondary mediators in Type 2 H
- platelet activating factors
- Leukotrienes
- Prostaglandins
- TH2 cytokines (IL-4, 5, 13, GM-CSF)
Primary mediator; causes constriction of smooth muscles, vasodilation and activates enzymes for tissue breakdown
Histamine
Effect of bronchiole constriction by histamine
Wheezing
Effect of constriction of intestines by histamine
Cramps
Diarrhea
Effect of vasodilation by histamine
- Increased fluid into tissues causing increased swelling
- fluid in mucosa
Pre-formed mediators in granules (Type 1 H)
Primary mediators
Mediators formed after activation (Type 1 H)
Secondary mediators
Most severe type of allergy; acute reaction that involves multiple organs
Anaphylaxis
Described anaphylaxis as “without protection”
Paul-Jules Portier
Charles Robert Richet
Researchers first to show that a serum factor was responsible for type 1 reactions
Carl Wilhelm Prausnitz
Heinz Kustner
Reaction described by Prausnitz and Kustner
Passive cutaneous anaphylaxis
What is the passive cutaneous anaphylaxis?
Serum from Kustner who was allergic to fish was injected to Prausnitz
A later exposure to fish antigen at the same site resulted in an allergic skin reaction.
Type of anaphylaxis; target organ responds to direct contact with allergen
Localized anaphylaxis
Effect of localized anaphylaxis in the digestive tract
Vomiting
Cramping
Diarrhea
Effect of localized anaphylaxis in the skin
Reddened, inflamed area resulting in itching
Effect of localized anaphylaxis in the airway
Sneezing and rhinitis OR wheezing and asthma
Effect of systemic anaphylaxis
Systemic vasodilation and smooth muscle contraction leading to severe bronchiole constriction, edema and shock
Systemic anaphylaxis is similar to __________
Systemic inflammation
Treatments for Type 1
Pharmacotherapy
Immunotherapy
Drugs used in pharmacotherapy to treat Type 1
Antihistamines Bronchodilators Corticosteroids Decongestants Epinephrine
ABCDE
Drugs that block histamine receptors
Antihistamines
First line of defense against hypersensitivity
Avoidance of known allergens
AKA Immunotherapy
Desensitization/Hyposensitization/Allergy shots
What happens in Desensitization?
Repeated injections of allergen to reduce the IgE on mast cells and produce IgG
What is the mechanism in using anti-IgE monoclonal antibodies to treat Type 1 reactions?
The anti-IgE monoclonal antibody combines with IgE at the same site that IgE would normally use to bind to receptors on mast cells. Blocking of this site does not allow IgE to bind to mast cells, alleviating allergic symptoms.
Tests for immediate hypersensitivity
In vivo test
In vitro test
In vivo tests for immediate hypersensitivity
Direct skin testing
Cutaneous/Prick Test
Intradermal
Most specific and least expensive in vivo test for type 1 reactions
Direct skin testing
Positive for Cutaneous/Prick test for type 1 reactions
Greater than 3 mm in diameter
OR
3 mm higher than the control
In vivo test for type 1 reactions; uses more concentration of allergen
Intradermal
Positive for intradermal test for in vivo type 1 reactions
Wheal that is 3 mm higher than the control
What is measured in the in vitro tests for type 1 reactions
Total IgE
Allergen-specific IgE
Tests in the in vitro testing for type 1 reaction
Radioimmunosorbent test (RIST) Radioallergosorbent test (RAST)
Test for total IgE
RIST
Test for allergen-specific IgE
RAST
In vitro test for Type 1 reactions; allows multiple allergens; diagnosis with a low sample volume
Microarray test
AKA Antibody-mediated cytotoxicity
Type II Hypersensitivity
What happens in drug reactions that causes Type II hypersensitivity
Drug binds to RBC surface and antibody against drug binds then causes lysis of RBC
Blood group systems most commonly associated with transfusion reactions
Duffy ABO Rh Kell Kidd
DARKK
Mechanism involved in Goodpasteur’s syndrome
Ab reacts with basement membrane protein which triggers complement activation resulting to inflammation and deposition of IgG
Tests for Type II
DAT
IAT
Used in DAT for Type II testing
- Polyspecific AHG (Abs to IgG, C3b, C3d)
- monospecific AHG
Method used to detect transfusion reactions, HDN, and autoimmune hemolytic anemia
DAT
Method used in crossmatching of blood to prevent a transfusion reaction
IAT
Hypersensitivity where a large amount of SOLUBLE antigen and antibodies form complexes in blood
Type III/Immune Complex Disease
Where can immune complexes be deposited of not eliminated?
Capillaries and joints where they can trigger inflammation
Process of degranulation and triggering of inflammation of neutrophils and macrophages when they are unable to phagocytize the immune complexes
Frustrated phagocytosis
Localized diseases caused by immune complexes
Arthritis
Glomerulonephritis
Deposition of immune complexes in joints causing local inflammation
Arthritis
Deposition of immune complexes in the kidneys cause __________
Glomerulonephritis
Type III reaction caused by passive immunization with animal serum, usually horse or bovine
Serum sickness
Type III reactions can be triggered by either ________ or ________ antigens
Autologous
Heterologous
Autoimmune diseases that are Type III reactions
- Systemic Lupus Erythematosus
- Rheumatoid arthritis
Tests for Type III hypersensitivity
- Fluorescent staining of tissue sections
- Agglutination reactions
- Measuring C’ levels
First described Type 4 hypersensitivity
Robert Koch
How did Robert Koch discover type IV hypersensitivity?
Patients with Mycobacterium tuberculosis developed a localized inflammatory response when injected intradermally with a filtrate from the organism
Leukocyte associated with type 4 hypersensitivity
Sensitized T cells, specifically, Th1 cells
True/False. Antibody and complement are directly involved in Type 4 Hypersensitivity
False
Ab and C’ are NOT directly involved
True/False. Type 4 reactions can be transferred through the serum.
False
The reaction CANNOT be transferred by serum, only through TRANSFER OF T LYMPHOCYTES
In delayed type hypersensitivity (DTH), ____ cells release _______ to activate ________ causing inflammation and tissue damage
Th1, cytokines, macrophages
In DTH, continued macrophage activation can lead to
Chronic inflammation
In DTH, chronic inflammation can lead to
Tissue lesions
Scarring
Granuloma formation
How many hours until DTH response arises after exposure?
72 hours
Generated by dendritic cells during sensitization stage against DTH antigens
Memory Th1 cells
Cells that can activate macrophages and trigger inflammatory response in DTH
Memory Th1 cells
When will DTH occur?
During the secondary contact
Cytokines by memory Th1 cells that cause tissue destruction and inflammation
IFN-gamma
TNF-alpha
TNF-beta
Cytokine by memory Th1 cells that activate cytotoxic T lymphocytes (CTLs)
IL-2
Cytokine by memory Th1 cells for macrophage recruitment
Chemokines
Cytokines by memory Th1 cells for increased monocyte/macrophage
IL-3
GM-CSF
3 causes for Contact Dermatitis
Poison ivy
Poison oak
Poison sumac
iOS
In contact dermatitis, small molecules acts as ______ and complex with skin proteins to be taken up by ___________, which is an APC, and presented to Th1 cells for sensitization
Haptens
Langerhans cell
Type 4 reaction; due to inhaled allergens; allergic disease of the lung parenchyma
Hypersensitivity pneumonitis
Other names for Hypersensitivity pneumonitis
Farmer’s Lung
Pigeon breeders disease
Humidifier lung disease
Type 4 reaction; soluble antigens from Mtb induce a reaction in people who have or have had tuberculosis
Tuberculin-type Hypersensitivity
What is the antigen in the tuberculin-type hypersensitivity?
Purified protein derivative (PPD) from the cell wall of the organism
DTH is a type of immune response classified by \_\_\_\_\_\_ and \_\_\_\_\_\_ activation that results in tissue damage.
Th1
Macrophage
Tests for type 4 reactions
Patch test
Mantoux method
Gold standard in testing contact dermatitis
Patch test
How is the patch test done?
Non-absorbent pad wil allergen is applied on the patient’s back, reaction is checked over the next 48, 96, and 120 hours
Amount of antigen injected intradermally in Mantoux method for type 4
0.1 mL
Positive for Mantoux method
Induration of 5 mm or more
At what time is the test site read in Mantoux method?
48 and 72 hours
Antigens commonly used in Mantoux method
- Candida albicans
- Tetanus toxoid
- Tuberculin
- Fungal antigens (trichophyton & histoplasmin)
