Allergy and Hypersensitivity Flashcards
What is hypersensitivity?
an inappropriate immune response to antigens that pose little to no threat
Type 1 Hypersensitivity immune mediator
IgE
Type 1 is initiated by?
an interaction between an IgE Ab and a multivalent antigen
Common allergic reaction
hay fever, asthma, eczema, bee stings, hives, food allergies
What type of individuals are genetically more susceptible to allergens?
Atopic
Atopic individuals
- Healthy individuals only produce IgE in regards to parasitic infections
- Atopic individuals produce IgE against common environmental antigens
Allergens
- are non-parasitic antigens
- soluble proteins or glycoproteins
- Many antigenic sites per molecule
- Often have intrinsic enzymatic properties
- Contain potential PAMPs, stimulating innate immunity
Type 1 reaction
- IgE antibodies act by cross-linking Fce receptors on the surfaces of innate immune cells
IgE cross-linking to FceR1
- causes degranulation
- granule contents released
Granule contents released
histamine heparin proteases leukotrienes prostaglandins chemokines
Mediators
act on surrounding tissues and cells to cause symptoms
FceR1
- high-affinity iGe receptor
- found on mast cells, eosinophils, and basophils
- linking receptors trigger Lyn-mediated phosphorylation of ITAMS
- triggers signaling pathway, leading to allergic effects
Activate mast cells leads to
- tissue changes remodeling
- Acute changes in function
- Inflammation
Type of mediators
- Histamines
- Leukotrienes and Prostaglandins
- Cytokines and Chemokine
Histamines
are formed by decarboxylation of histidine amino acid and is a major component of mast cell granules
What happens when binds to histamine receptors
- contraction of intestinal and bronchial smooth muscles, increased permeability of venues, and mucous secretion
- increase vasopermeability and vasodilation, and increase stomach acid
- mediates mast cell chemotaxis
Leukotrienes and Prostaglandins
- second messengers and are formed when membrane phospholipids are enzymatically cleaved
- active at nanomole levels
- more potent stimulators of vascular permeability and mucous secretion
Major cause of asthma symptoms
Leukotrienes and prostaglandins
IL-4 and IL-13
stimulates Th2 responses to increase IgE production by b cells
IL-5
recruits and activates eosinophils
TNF-alpha
Contribute to shock in systemic anaphylaxis
CXCL-8
acts as a chemotactic factor, attracting other cells
GM-CSF
Stimulates production and activation of myeloid cells (granulocytes)
Type 1 Early response
- occur within minutes of allergen response
- Mediated by mast cell granule release of histamine, leukotrienes, and prostoglandins
Type 1 late response
- Hours later
- A result of recruited cells
- Cytokines release from mast cells increase expression of chemokines and CAMs on endothelium facilitating influx of neutrophils, eosinophils, and Th2 cells
- Eosinophils play a large role in late-phase recruiting neutrophils and degranulation
Type 1 hypersensitivity Reaction categories
- Systemic anaphylaxis
- Localized hypersensitivity
- Food allergies
Systemic anaphylaxis
- initiated by an injected or gut-absorbed allergen
- Symptoms: labored respiration, drop in blood pressure leading to anaphylactic shock, contraction of smooth muscles leading to bronchiolar constriction
- Treatment: Epinephrine ( steroid) target inflammatory (TNF-a)
Localized hypersensitivity reactions
- Pathology is limited to a specific tissue or organ
- Includes allergic rhinitis (hay fever), allergic conjunctivitis, asthma, atopic dermatitis (eczema) atopic urticaria (hives) and food allergens
- Symptoms: result from release of mediators in immediate exposure area
Food allergies
- Food allergens are often water-soluble glycoproteins stable to heat, acid, and proteases
- Can cause vomiting and diarrhea (constriction of muscles, mucous increase) and gut vasodilation
Environmental and genetic basis for type 1
- air pollution to diet
- genetics both influence susceptibility to allergies
Hygiene Hypothesis
- exposure to some pathogens early in life provides a better T-cell balance
- Avoids dominance of Th2 subset, which promotes IgE production by B cells
- developed countries have an increase in allergies
Type 1 diagnosis
- skin testing
- swelling and redness
- quantify total or allergen-specific IgE serum levels
Type 1 treatments
- Antihistamines, leukotriene antagonist, and inhalation corticosteroids
- Desensitization immunotherapy (repeat low-dose exposure may induce Th1 and Treg cells) (anti-IgE antibodies that bind and inhibit the allergen-specific IgE from binding to mast cell FceR molecules
Type II Hypersensitivity
Antibody-mediated cell cytoxicity
- Complement activation or NK activated through ADCC
- Transfusion reactions
- IgG or IgM
Transfusion
- Adults possess antibodies to the blood type they do not have
- Antibodies will quickly attach to the donor blood cells and trigger complement
- The degraded RBC components can build up to toxic levels
Hemolytic Disease of the new born
- Develops when maternal IgG Ab specific to the expressed Rh allele crosses the placentia
- First pregnancy mother is Rh(-) and her fetus is Rh(+) she will be exposed to the antigen. Anti-Rh IgG and memory cells
- Second pregnancy her Fetus is (+), her memory cells will recognize the antigen and produce Anti-Rh and will cause the fetus blood to lyse
- Rho gam shot
- UV light
Type III hypersensitivity
- Immune complexes
- May deposit in tissues if they aren’t cleared correctly
- Release of inflammatory mediators and vasoactive mediators
Type III symptoms
- Vasculitis if in blood vessel
- Glomerulonephritis if in kidney
- Arthritis if in joints
Immune complex-mediated hypersensitivity
can resolve spontaneously
- eventually complexes are cleared so long as Ag eventually goes away
Autoantigens can be involved in immune complex-mediated reactions
Ag can’t completely go away in such a case
Type IV Hypersensitivity
- Delayed Type (DTH)
- Purely cell mediated
- Initiated by T cells
Type IV is characterized by
recruitment of macrophages at inflammation site
Example of Type IV
poison ivy
Sensitization Phase
- Initiation involves sensitization by an antigen
- Initial exposure triggers production of a T-cell response
- CD4+ Th1 subset
- 1-2 weeks
Effector Phase
- induced by secondary exposure to a sensitizing ag
- induces production of Th1 inflammatory cytokines
