Chapter 14: Allergic Diseases and Hypersensitivity Reactions Flashcards
What is a hypersensitive reaction? What are the four types and their mediators?
- Inappropriate or exaggerated immune response towards an innocuous antigen/allergen
- Type I mediated by IgE, Type II mediated by IgG or IgM, Type III immune complex mediated, Type IV T cell mediated
What are type I allergic diseases?
- IgE mediated allergic reactions
- Usually occur due to a person becoming sensitive resulting in IgE production and production of memory B cells
- Atopy - Genetically based tendency to produce IgE mediated reactions
- All IgE mediated responses involve Mast-cell degranulated but symptoms vary based on route of entry
Outline the steps involved in an allergic reaction.
- Allergen is encountered and presents it to TH2
- B cell is activated by TH2
- B cell proliferates and produces plasma cells to secrete IgE
- IgE binds to mast cells
- Subsequent exposure results in allergic symptoms
What causes allergens?
- No physical, chemical, or functional feature has been found that is common to all allergens
- Many clinically significant Allergens are proteases
- One ubiquitous protease allergen is cysteine protease Der p 1. Causes allergy to dust mites and is present in 20% of americans
Outline the steps involved in Der p 1 eliciting an allergic reaction.
- Der p 1 cleaves occludin in tight junctions and enter mucosa
- Dendritic cell primes T cells in lymph node
- IgE specific for Der p 1 travels to mucosa
- Der p 1 specific IgE binds to mast cells triggering degranulation
Do genetic factors contribute to IgE mediated allergic diseases?
Yes, many genes have an important role in dealing with asthma, T cell differentiation, and other functions
What other factors contribute to IgE mediated allergic diseases?
Environment, children raised in rural settings are less likely to have allergic diseases than children raised in urban areas
What are the two possible results of being exposed to an allergen?
Immediate reaction
- Due IgE mediated mast cells activation and starts within seconds
- Activity of histamine, prostaglandins, and other mediators that cause a rapid increase in vascular permeability and contraction of smooth muscle
Late phase reaction
- Due to continuous release of inflammatory mediators by mast cells and recruit eosinophils, basophils, neutrophils, monocytes, and lymphocytes
- Mediators include leukotrienes, chemokines, and cytokines
- Resistant to anti-histamines
- Can lead to chronic inflammatory response
What is allergic rhinitis?
- IgE antibodies recruit signaling molecules which recruit inflammatory cells that secrete soluble mediators that can lead to sneezing congestion and more
(IMAGE 10)
Outline the steps involved in signal induction by FceRI
- Cross linking by receptor recruits and activates Syk tyrosine kinase
- Activation of PLC-y
- Generation of IP3 which releases calcium
- Cytosolic calcium Induces secretion of mast cell’s granules
How does mast cells activation and granule release affect the gastrointestinal tract, Eyes, Nasal, and air passageway, and blood vessels?
What molecules are released by the activation of mast cells?
- Enzymes, toxic mediators, Cytokines, chemokines, and lipid mediators
What are the possible routes of entry for an allergen?
- Allergens can encounter connective tissue mast cells intravenously or subcutaneously
- Allergens can encounter mucosal mast cells via inhalation or ingestion
What molecules can be released by eosinophils and basophils? what do they cause in an allergic reaction?
- Release ezymes, toxic proteins, Cytokines, chemokines, and lipid mediators
- Cause inflammation and tissue damage in allergic reactions
Compare a normal airway and an asthmatic airway.
Normal:
- Thin layer of mucous and a low amount of mast cells and eosinophils under epithelial layer
- Good airflow with no blockage
Asthmatic:
- Mucous hypersecretion
- Eosinohil inflammation
- Restricted airway
What leads to the differences that can be observed in someone with mild asthma vs chronic asthma?
- Increased mucus
- Increased fibrosis
- Increased inflammatory cells (CD4 and eosinophils
- Increased muscle thickness
What happens when someone with hives encounters pollen or another allergen?
- Pollen enters the body and is taken up by mast cells resulting in the release of histamines which increases blood vessel impermeability resulting in redness and swelling
What happens as lesions progress in individuals with eczema?
- Healthy skin gets reduced barrier function as barrier integrity is disrupted which leads to ILCs releasing inflammatory molecules
How does an IgE mediated allergic reaction occur to food?
- Allergen is taken up by dendritic cell and eventually Mast cells will get IgE antibodies and it will cross link resulting in vasodilation
What is anaphylaxis?
- Systematic allergic reaction
- Occurs when Allergens enter the bloodstream directly or when the allergen is rapidly absorbed by the gut (bee sting or eating food)
- Mast cells associated with blood vessels throughout the body are activated
- Acute urticaria occurs when the allergen is delivered to the skin from the blood stream
- Anaphylactic shock occurs due to widespread increase in vascular permeability and smooth muscle contraction
- Drop in blood pressure
- Constriction of airways
What receptors does epinephrine target and what are the results?
What can be targeted by allergen immunotherapy to treat allergic diseases?
What is type II hypersensitivity?
- Mediated by IgG and IgM
- In susceptible individuals, binding of the drug to the surface of circulating red blood cells or platelets cause the destruction of the cells by antibody mediated mechanisms
What is type III hypersensitivity?
- Mediated by immune complexes or antibody: antigen aggregates
- Pathogenic potential is determined in part by their size and by the amount, and affinity, and isotypes of the responding antibody
- Immune complexes are deposited in tissue
Local
- Arthus reaction (Low dose)
- The immune complexes are formed only close to site of injection where they activate mast cells with Fcy receptors
Systematic
- Serum sickness
- Immune complexes from throughout the body
- Follows the admin of large quantities of poorly catabolized antigens
Pathogenic immune complexes from due to antigen persistence during infection
What is type IV sensitivity?
- Mediated by TH1 cells and cytotoxic CD8 T cells
- Delayed hypersensitivity
- Antigen is injected into the skin and reaction occurs hours to days later
- Specific T cells are rare and because there is little inflammation to attract cells into site, can take several hours for a T cell to correct specification
What are cellular hypersensitivity reactions mediated by?
- Antigen specific effector T cells
How is an antigen processed by tissue macrophages? And how does it stimulate TH1 cells?
What is contact hypersensitivity?
- Antigen absorbed into the skin
- Activation of CD4 or CD8 cells
- Depends on antigen processing pathway
- Poison ivy or poison oak
Hapten - Small molecules that illicit an immune response only when attached to a carrier protein
