Lecture 23 Flashcards
State the 3 characteristics that usually accompany an acquired immune response that causes and allergy.
(which Ig type)
(which cells types)
(T cell response type and the 3 IL’s it creates)
- presence of allergen-specific IgE
- Mast cells and Eosinophils (being recruited/activated)
- Th2 responses and IL-4, IL-5, and IL 13
State the 2 common mechanistic aspects of allergic diseases
- Results in harmful immune responses
- Noninfectious Ags drive the immune responses
- IgE is generated
State the 2 type of molecules that allergens can be. Which phenotype bias is related to most allergic immune reactions?
Proteins and Glycoproteins
Th2 phenotype
Allergens can activate innate immune responses by which 2 activities?
Intrinsic enzymatic activity
Activation of PRRs (pattern-recognition receptors)
Indoor allergens are usually associated with ____ while outdoor allergens are usually associated with_____ _____.
Asthma
Allergic rhinitis
What characteristic of some allergen helps them to cross skin or mucosal barriers? Why are most allergens contained within particles?
protease activity
Because small particles are aerodynamic and can be spread to mucosa in the nasal/bronchial areas more easily
Atopy leads to ____-mediated allergic inflammation. State the 4 factors that influence the development of atopy.
Th2
- Genetic factors (HLA, FcR1-B, IL-4, CD14 mutations)
- Environmental factors (allergen sensitization, few siblings, excessive hygiene, Antibiotic before age 2)
- Defects in Target organs (compromised epithelium in skin/GI tract)
- Triggers (Viral infections, Pollutants, Exposure to allegens)
State some factors that favor the Th1 phenotype and what favoring this phenotype leads to. Do the same for the Th2 phenotype.
Th1 phenotype: leads to protective immunity Older siblings Day Care exposure TB, Measles, Hepatitis A infection Rural environment
Th2 phenotype: leads to allergic diseases Antibiotic use Diet Sensitization to household allergens Urban environment
What term describes the presence of a type I hypersensitivity reaction to an allergen? What type of test can be conducted to demonstrate whether or not a pt exhibits this term?
Atopy
Skin prick test
State the chances of the following atopic parent combinations producing a child that is atopic
2 atopic parents:
1 atopic parent:
0 atopic parents:
2 atopic parents: 75%
1 atopic parent: 50%
0 atopic parents: 25%
State the 4 genes that are known to be involved with the inheritance pattern of allergic diseases
- The Beta chain of the receptor for IgE (FcSigmaRIbeta)
- IL-4 gene
- HLA-DR alleles
- CD14 gene
Describe how a polymorphism on the CD14 gene can affect the allergic tendency of a person.
CD14 is a PART of the receptor for bacterial cell wall LPS (lipopolysaccharides)
Different polymorphisms of CD14 could trigger an exaggerated immune response to an LPS molecule that is not actually harmful
What percentage of Allergic development comes from genetics and what percentage comes from the environment?
Genetics: 20%
Environment: 80%
True or False:
The month you are born in can affect your tendency to develop an allergy. explain.
True
ex. children born during the months of birch pollen release are much more likely to develop a birch pollen allergy due to “allergen sensitization” occuring
State another name for the “hygiene hypothesis”. State the 2 mechanisms that the hygiene hypothesis attributes the to increasing incidence of allergic diseases
Hygiene hypothesis aka germless theory
- Shift in immune system phenotype toward Th2 type responses
- Decrease in T reg cells that would usually calm the exaggerated allergic immune reactions
What is the Main postulate of the hygiene hypothesis? explain this postulate in terms of Th1 and Th2 phenotypes
Main postulate: increased incidence of allergy is associated with the decrease in exposure to common infections during early life
Basically, infections in early childhood stimulate Th1 type responses and shift the immune phenotype balance from Th2 (favored during neonate age) toward Th1
What is BCG and how is it related to allergic reactions?
BCG is a bacterial strain that has been shown to cause the proliferation of T regulatory cells
Early studies of BCG vaccination have shown that they can decrease the severity or eliminate allergic reactions in most people.
All of the following are type I hypersensitivity reactions with IgE as effectors. State the 2 effector cells that IgE can be found on in the following conditions.
Anaphylaxis:
Asthma and Hayfever:
Food Allergy:
Anaphylaxis: IgE on basophils and mast cells
Asthma and Hayfever: IgE on Mast cells and Th2 cells
Food Allergy: IgE on Mast cells and Th2 cells
For Mast cells, state the following.
Site of Maturation: Does the cell circulate? Are it's mature cells recruited into tissues? Do it's mature cells reside in CT? Can it's mature cells proliferate?
Mast Cells
Site of Maturation: CT Does the cell circulate? No Are it's mature cells recruited into tissues? No Do it's mature cells reside in CT? Yes Can it's mature cells proliferate? Yes
For Basophils, state the following.
Site of Maturation: Does the cell circulate? Are it's mature cells recruited into tissues? Do it's mature cells reside in CT? Can it's mature cells proliferate?
Basophils
Site of Maturation: Bone Marrow
Does the cell circulate? Yes (0.5% of blood leukocytes)
Are it’s mature cells recruited into tissues? Yes
Do it’s mature cells reside in CT? No
Can it’s mature cells proliferate? No
For Eosinophils, state the following.
Site of Maturation: Does the cell circulate? Are it's mature cells recruited into tissues? Do it's mature cells reside in CT? Can it's mature cells proliferate?
Eosinophils
Site of Maturation: Bone Marrow
Does the cell circulate? Yes (2% of blood leukocytes)
Are it’s mature cells recruited into tissues? Yes
Do it’s mature cells reside in CT? Yes
Can it’s mature cells proliferate? No
Which cell type features the following list of “major granule components”?
Histamine, Heparin and/or Chondroitin Sulfate, and Proteases
Mast Cells
Histamine, Heparin and/or Chondroitin Sulfate, and Proteases
Which cell type features the following list of “major granule components”?
Major Basic Protein, Eosinophil cationic protein, peroxidases, hydrolases, lysophospholipase
Eosinophils
Major Basic Protein, Eosinophil cationic protein, peroxidases, hydrolases, lysophospholipase
Which cell type features the following list of “major granule components”?
Histamine, Chondroitin Sulfate, and Proteases
Basophils
Histamine, Chondroitin Sulfate, and Proteases
For Mast cells, answer the following.
Life span:
Major development factor (cytokine):
Level of FcERI expression:
Mast Cells
Life span: Weeks to Months
Major development factor (cytokine): Stem cell factor and IL-3
Level of FcERI expression: High levels
For Basophils, answer the following.
Life span:
Major development factor (cytokine):
Level of FcERI expression:
Basophils
Life span: Days
Major development factor (cytokine): IL-3
Level of FcERI expression: High levels
For Eosinophils, answer the following.
Life span:
Major development factor (cytokine):
Level of FcERI expression:
Eosinophils
Life span: Days to weeks
Major development factor (cytokine): IL-5
Level of FcERI expression: Low levels
During a Type I hypersensitivity reaction, what Cytokine is responsible for causing the B cells to undergo Ab class switching? what 2 Ig classes does it switch between?
IL-4
Switches from IgM to IgE
Define Degranulation and include which type of hypersensitivity reaction it occurs during. What cell undergoes degranulation and is also referred to as a “sentinel cell”?
Degranulation: Occurs during a secondary exposure to an allergen that causes a type I hypersensitivity reaction and triggers mast cells to release their granule contents
Mast cells = “sentinel cells”
Match the following to the phase of a type I hypersensitivity reaction is is responsible for inducing. Include the symptoms that each of these induce.
Biogenic amines and lipid mediators:
Cytokines and lipid mediators:
Biogenic amines and lipid mediators (in granules): Immediate reaction (early phase)
Vascular/Smooth muscle response
Cytokines and lipid mediators: Late phase reaction
Inflammation
Vascular leakage, Bronchoconstriction, and intestinal hypermotility are all consistent with which phase of a type I hypersensitivity reaction?
Immediate Response (early phase)
(the Bronchoconstriction is from smooth muscles in arteries, NOT the inflammation that occurs in the late phase of type I reactions)
Put the following characteristics in the Immediate phase or late phase of a type I hypersensitivity reaction.
Intestinal hypermotility Inflammation Vasodilation Broncho-constriction Vascular Leak Tissue Damage
Immediate Phase: Vasodilation Vascular Leak Broncho-constriction Intestinal hypermotility
Late Phase:
Inflammation
Tissue Damage
Describe the process of sensitization to allergens (beginning with DC’s and ending with Plasma cells)
Include the various cytokines that are produced
- DC pick up the allergen and bring it to a LN to present it in Class II MHC AND they secrete IL-4
- The TCR of Naive T cells interacts with the MHC class II molecule of the DC to become activated and the IL-4 causes the T cell to become a Th2 cell
- The Th2 cells then secretes IL-4 and IL-13 AND interacts with Naive B cells to activate them
- Activated B cells switch to IgE production and become plasma cells or memory B cells
State the 3 events that occur when Th2 cells secrete IL-4 and IL-13.
- Production of IgE (from B cells)
- Development of Mast Cells
- Overproduction of mucus
State the Cytokine(s) that induce the following events
Development and accumulation of Eosinophils and Basophils:
Airway hyperresponsiveness:
Development and accumulation of Eosinophils and Basophils: IL-4, IL-5, and IL-13
Airway hyperresponsiveness: IL-13
Describe the characteristic of FcERI that causes the rapid reaction of the Immediate reaction phase of a type I hypersensitivity reaction. What FcERI action leads to the degranulation of Mast cells and Basophils?
FcERI have a very high affinity for the Fc portion of IgE (so the reaction happens quickly)
Cross linking of FcERI leads to the degranulation of Mast cells and Basophils
State the 2 main preformed cytokines that Mast cells use to induce the immediate/early phase of a type I hypersensitivity reaction. Describe the function of these 2 cytokines.
Histamine: causes smooth muscle contraction and increases vascular permeability
TNFalpha: activates the adhesion molecules in the endothelium of blood vessels in order to recruit immun cells out of circulation and into the “infection” site
For the following Mast cell mediator, state it’s function
IL-1:
IL-1: causes inflammation
For the following Mast cell mediator, state it’s function
Tryptase:
Tryptase: has trypsin-like activity that causes anaphylaxis and urticaria (hives)
For the following Mast cell mediator, state it’s function
Prostaglandin E2 (PGE2):
Prostaglandin E2 (PGE2): causes pain and increases vascular permeability
For the following Mast cell mediator, state it’s function
PGD2 and Leukotrienes, LT (C4, D4, E4):
PGD2 and Leukotrienes, LT (C4, D4, E4): causes smooth muscle contraction and Increases vascular permeability
For the following Mast cell mediator, state it’s function
Bradykinin:
Bradykinin: causes vasodilation and smooth muscle contraction
For the following Mast cell mediator, state it’s function
IL-5:
IL-5: signals for survival/proliferation of Eosinophils in sputum
During chronic disease development, state the cell that secretes the following. Which of these enters the airway to secrete its product?
TNFalpha
IL-4, IL-5, and IL-13
Mediators (hint: its not mast cells)
Macrophages secrete TNFalpha
Th2 cells secrete IL-4, IL-5, and IL-13
Eosinophils enter the airway and degranulate to release their mediators
Chronic allergic disease processes leads to _______ and ____airway responsiveness to the allergen. Further progression of this chronic inflammation can lead to Airway _____.
Obstruction
Increased
Remodeling
During the process of tissue remodeling, describe the effect it has on the following cell types.
Tissue Fibroblasts:
Goblet Cells:
Smooth Muscle:
Tissue Fibroblasts: produce more collagen than normal and deposit in the damaged airway (causing structural changes)
Goblet Cells: produce more mucus
Smooth Muscle: display hypertrophy and hyperplasia
What type of conditions is desensitization treatment for? Briefly describe the process of this treatment
life-threatening allergy reactions that display IgE hypersensitivity
Injecting a pt with very very small doses of the allergen they are allergic to, and slightly increasing the dose each time the allergen is administered
Describe the following terms as they pertain to desensitization treatment
Maximum dose:
Maintenance dose:
Maximum dose: the largest dose of allergen that the patient will receive (usually reached 6-10 weeks after treatment begins)
Maintenance dose: the dose given to the pt to maintain their desensitized state for the Ag (given monthly for 2/3 years)
Describe the following mechanism of desensitization treatment for allergies.
IgG Blocking Abs:
IgG Blocking Abs: When desensitization treatment is occuring, IgG Abs develop and compete with the pathogenic IgE Abs for allergen binding sites
This reduces the severity/level of IgE mediated allergic response to the allergen
Describe the following mechanism of desensitization treatment for allergies.
Regulation:
Regulation: During desensitization treatment, the repeated exposure to the allergen increases the number of Treg cells in the pt.
This causes a stronger “dampening” of the inflammation/infiltration of the allergic response
Describe the following mechanism of desensitization treatment for allergies.
Immune Deviation:
Immune Deviation: Administering substances that invoke Th1 responses in an effort to shift the pt’s immune response to a balance between Th1 and Th2 (instead of the overactive Th2 response that causes allergies)
(ex. japanese TB prisoners stopped having allergies)
