Hypersensitivity Flashcards
Describe the difference between a Pathogenic Antigen and an Allergen
Both are molecules capable of inducing an immune response from pathogen (antigen) vs from non-pathogen (allergen)
Hypersensitivity
Exaggerated response to a harmless antigen that results in injury to the tissue, disease, or even death
Characteristics of Type 1 Hypersensitivity
IgE, Soluble molecule antigen, IgE induced mast cell activation mechanism, Ex Allergic rhinitis, allergic asthma
Characteristics of Type 2 Hypersensitivity
IgG/IgM, Cell associated molecule antigen, Complement mediated phagocytosis mechanism, Ex Chronic urticaria (auto antibodies)
Characteristics of Type 3 Hypersensitivity
IgG/IgM, Soluble Molecule, Tissue damage induced by immune complexes mechanism, ex serum sickness, arthus reaction
Characteristics of Type 4 Hypersensitivity
T cells, Soluble or cell associated molecule antigen, T cell mediated inflammation or cytotoxicity mechanism, Ex Multiple sclerosis, contact dermatitis, crohn’s disease
How does IgE respond in a Type 1 Hypersensitivity reaction?
IgE binds to FcEpsilonR on mast cells and basophils
Cross-linking of Mast Cell IgE with allergen triggers clinical signs of type 1 HS
Characteristic of atopic individuals
1 - IgE immune response to allergen develops-characteristic of atopic individuals
2 - IgE binds to FcEpsilonR on mast cells and basophils
3 - Subsequent allergen exposure results in cross-linking of two+ IgE on surface
4 - Cross-linking triggers immediated release of preformed mediators - Fast (seconds to minutes)
5 - Activated cells also synthesize late mediators (6-8hrs) from membrane phospholipids
What are the phases of type 1 hypersensitivity?
Immediate/Initial vs Late phase
What are mediators of type 1 hypersensitivity?
Immediate - fast released, preformed mediators (Granule contents - Histamine, Proteases, Chemotatic factors)
Late - synthesized from membrane phospholipids
Anaphylaxis
Caused by? systemic release of histamine
Examples of Type 1 Hypersensitivity
Rhinitis (pollen), Food allergies (nuts)
- from localized release of histamine in nasal area or GI tract
Skin testing/Patch test Type 1 Hypersensitivity Testing
- Gold standard
- Inject allergen under skin, wheal and flare develop within 15 minutes in sensitized individuals
Problems - Variability (site, amount of allergen), severe reaction
Type 1 Hypersensitivity testing
In vivo vs in vitro
Vivo - Skin testing/ Patch test
Vitro - RIST/RAST
RIST vs RAST
RIST - Radio Immuno Sorbent Test : Measure total IgE
RAST - Radio Allergo Sorbent Test : Measure antigen-specific IgE
RIST results
<2 = Normal in infants = Not allergic >10 = high in infants = highly likely allergy >/= 100 = Possible allergy = additional testing >/= 400 = Abnormally high in adults = Highly likely atopy
Mechanisms of Type 2 Hypersensitivity reactions
Killing of target cell by effector-macrophage/NK cell, Complement mediated lysis, Receptor specific autoantibody interferes with signal transduction
type 2 Hypersensitivity examples
- Transfusion reactions
- Hemolytic disease of the newborn (HDN)
- Autoimmune hemolytic anemia (including warm and cold autoagglutinins)
- Goodpasture’ssyndrome
- Hashimoto’s disease
- Myasthenia gravis
Hemolytic disease of the newborn
appears in infants whose mothers have been exposed to blood-group antigens on the baby’s cells that differ from their own. The mother makes IgG antibodies in response to these antigens that cross the placenta to destroy the fetal RBCs
- Exposure usually occurs during the birth process when fetal cells leak into the mother’s circulation. Typically, the first child is unaffected; however, the second and later children have an increased risk of the disease because of an anamnestic re- sponse
Treatment for severe HDN
involves an exchange transfusion to replace antibody-coated RBCs. If serum antibody titrations during the pregnancy in- dicate a high level of circulating antibody, intrauterine trans- fusions can be performed
HDN Prevention
To prevent the consequences of HDN, all women should be screened at the onset of pregnancy. If they are Rh-negative, they should be tested for the presence of anti-D antibodies on a monthly basis. In current practice, anti-D immune globulin, called Rhogam, is administered prophylactically at 28 weeks of gestation and within 72 hours following delivery.43 The mecha- nism by which Rhogam works is not completely known, but it is thought to facilitate clearance of the fetal RBCs through opsoniza- tion and therefore suppress production of maternal antibody
type 2 Hypersensitivity tests
Direct test (DAT), Coomb’s, Indirect test
characteristics of type 2 hypersensitivity tests
DAT - Need baby’s blood, detects in vivo binding of Ig to RBC
Coomb’s - Antiglobulin test (anti-IgG + anti-C3b), Followed by anti-igG alone or anti-C3b alone tests to determine if causative Ig is IgG or IgM
Indirect test - Need mom’s serum, detects ex vivo binding of Ig to RBC
Allergen
An antigen that triggers a type I hypersensitivity response
i.e., an allergy
Allergy immunotherapy (AIT)
Therapy involving administrationof increasing doses of an allergen over time with the goal of inducing immune tolerance to the allergen
Anaphylaxis
A life-threatening response to an allergen characterized by the systemic release of histamine
Arthus reaction
A type III hypersensitivity skin reaction that occurs when an animal has a large amount of circulating antibody and is exposed to the antigen intradermally, resulting in localized deposition of immune complexes
Atopy
An inherited tendency to respond to naturally occurring allergens; it results in the continual production of IgE
Autoimmune hemolytic anemia
An autoimmune disorder in which patients form antibodies that destroy their own red blood cells (RBCs)
Cold agglutinins
Antibodies that react below 30°C, typically formed in response to diseases such as Mycoplasma pneumonia and certain viral infections
Contact dermatitis
A delayed hypersensitivity reaction caused by T-cell sensitization to low molecular weight compounds, such as nickel and rubber, that come in contact with the skin.
Delayed hypersensitivity
Type IV or T-cell–mediated hypersensitivity; so named because its manifestations are not seen until 24 to 48 hours after exposure to the inducing antigen
Direct antiglobulin test (DAT)
A technique to determine in vivo attachment of antibody or complement to red blood cells (RBCs), using anti-human globulin to cause a visible agglutination reaction.
Granulomas
An organized cluster of inflammatory cells formed in some type IV hypersensitivity responses.
Hemolytic disease of the newborn (HDN)
A cytotoxic reaction that destroys an infant’s red blood cells (RBCs) because of placental transfer of maternal antibodies to Rh antigens
Histamine
A vasoactive amine released from mast cells and basophils during an allergic reaction
Hypersensitivity
A heightened state of immune responsiveness
Immediate hypersensitivity
Reaction to an allergen that occurs in minutes and can be life-threatening
Isohemagglutinins
Antibody that agglutinates red blood cells (RBCs) of other individuals of the same species
Leukotrienes (LT)
A class of secondary mediators released from mast cells and basophils during type I hypersensitivity reactions
Paroxysmal cold hemoglobinuria
A condition in which patients produce a biphasic autoantibody that binds to RBCs at cold temperatures and activates complement at 37°C to produce an intermittent hemolysis
Serum Sickness
A type III hypersensitivity reaction that results from the buildup of antibodies to animal serum used in passive immunization
Type 1 hypersensitivity
An allergic reaction in which antigen-specific IgE antibody binds to mast cells and basophils, triggering degranulation and the release of chemical mediators; also known as anaphylactic hypersensitivity
Type 2 hypersensitivity
An immune reaction in which IgG or IgM antibodies are produced to cell surface receptors, causing damage to the cells, dysfunction of the cells, or overstimulation
of the function of the cells; also known as antibody-mediated cytotoxic hypersensitivity
Type 3 hypersensitivity
An immune reaction in which IgG or IgM antibodies react with soluble antigens to form small complexes that precipitate in the tissues and activate complement to induce inflammation; also known as complex-mediated hypersensitivity
Type 4 hypersensitivity
A cell-mediated response involving the release of cytokines that induce inflammation and tissue damage 24 to 72 hours after contact with an antigen
Describe the difference between a Pathogenic Antigen and an Allergen
Both are molecules capable of inducing an immune response from pathogen (antigen) vs from non-pathogen (allergen)
Hypersensitivity
Exaggerated response to a harmless antigen that results in injury to the tissue, disease, or even death
Characteristics of Type 1 Hypersensitivity
IgE, Soluble molecule antigen, IgE induced mast cell activation mechanism, Ex Allergic rhinitis, allergic asthma
Characteristics of Type 2 Hypersensitivity
IgG/IgM, Cell associated molecule antigen, Complement mediated phagocytosis mechanism, Ex Chronic urticaria (auto antibodies)
Characteristics of Type 3 Hypersensitivity
IgG/IgM, Soluble Molecule, Tissue damage induced by immune complexes mechanism, ex serum sickness, arthus reaction
Characteristics of Type 4 Hypersensitivity
T cells, Soluble or cell associated molecule antigen, T cell mediated inflammation or cytotoxicity mechanism, Ex Multiple sclerosis, contact dermatitis, crohn’s disease
How does IgE respond in a Type 1 Hypersensitivity reaction?
IgE binds to FcEpsilonR on mast cells and basophils
Cross-linking of Mast Cell IgE with allergen triggers clinical signs of type 1 HS
Characteristic of atopic individuals
1 - IgE immune response to allergen develops-characteristic of atopic individuals
2 - IgE binds to FcEpsilonR on mast cells and basophils
3 - Subsequent allergen exposure results in cross-linking of two+ IgE on surface
4 - Cross-linking triggers immediated release of preformed mediators - Fast (seconds to minutes)
5 - Activated cells also synthesize late mediators (6-8hrs) from membrane phospholipids
What are the phases of type 1 hypersensitivity?
Immediate/Initial vs Late phase
What are mediators of type 1 hypersensitivity?
Immediate - fast released, preformed mediators (Granule contents - Histamine, Proteases, Chemotatic factors)
Late - synthesized from membrane phospholipids
Immediate vs delayed Hypersensitivity
Immediate (1-3) - symptoms develop within a few minutes to a few hours
Delayed (4) - manifestations are not seen until 24-48 hours after contact with antigen
What is the characteristic that all hypersensitivity reactions share
all have an aysmptomatic initial phase in which sensitization to Ag occurs
Which of the following is a general characteristic of
hypersensitivity reactions?
c. An exaggerated immune response to an antigen
Which of the following is associated with an increase
in IgE production?
b. Activation of Th2 cells
- Which of the following would cause a positive DAT test?
Presence of IgG on RBCs
b. Presence of C3b or C3d on RBCs
c. A transfusion reaction caused by preformed antibody
D. Any of the above
- All of the following are associated with type I hyper-
sensitivity except
a. release of preformed mediators from mast cells.
B. activation of complement.
c. cell-bound antibody bridged by antigen.
d. an inherited tendency to respond to allergens.
- Which of the following is associated with anaphylaxis?
a. Buildup of IgE on mast cells
- To determine if a patient is allergic to rye grass, the
best test to perform is the
b. skin prick test.
- Which condition would result in HDN?
d. Prior exposure to foreign RBC antigen
- What is the immune mechanism involved in type III
hypersensitivity reactions?
b. Deposition of immune complexes occurs in anti-body excess.
- What is the immune phenomenon associated with the Arthus Reaction?
c Deposition of immune complexes in blood vessels
10 . Which of the following conculsions can be drawn about a patient whose total IgE level was determined to be 150 IU/ml?
Antigen-specific testing should be done
- Which of the following explains the difference between type 2 and type 3 hypersensitivity reactions?
Type 2 involves cellular antigens
12 two days after administration of the PPD test, a female health-care worker developed an area of redness and induration 12 mm in size at the injection site. This result means that she has
been exposed to M tuberculosis
- A young woman developed red, itchy papules on her wrist 2 days after wearing a new bracelet. This reaction was caused by
an inflammatory response induced by cytokines released from Th1 cells
- Reactions to latex are caused by
type 1 hypersensitivity
15 To determine a cold agglutinin titer
patien serum should be separated from whole blood at 37c and tested at 4c
