Hypersensitivity Flashcards
ACID Acronym for Hypersensitivity Rxns
Type I = Anaphylactic and Atopic
Type II = Cytotoxic (antibody-mediated)
Type III = Immune Complex
Type IV = Delayed (T-cell mediated)
type I hypersensitivity is mediated by what class of immunoglobulin
IgE
examples of type I hypersensitivity reactions
- systemic anaphylaxis
- acute urticaria (hives)
- allergic rhinitis (hay fever)
- asthma
- food allergies
systemic anaphylaxis response
-edema
-increased vascular permeability
-tracheal occlusion
-circulatory collapse
-death
steps of type I hypersensitivity reactions
- initial allergen exposure (sensitization)
- IgE production (as a result of IL-4 and IL-13) by plasma cells
- IgE binds to mast cells
- allergen cross-link IgE on mast cells
- mast cells release mediators (DEGRANULATE) on 2nd exposure [release of histamine, PGE, LT, PAF, and cytokines]
- early phase effects and promotion of late phase effects
where does IgE bind to mast cells
Fc epsilon receptor
*occurs after INITIAL exposure to the allergen
what happens on FIRST exposure to an allergen in a type I HSR
IgE is produced, and the IgE attaches to the Fc epsilon receptor on mast cells
what happens on SECOND exposure to an allergen in type I HSR
*the allergen binds and cross-links the IgE on the mast cell surface
*this causes degranulation of mast cells, releasing cytokines and second messengers
degranulation is caused when ?
an antigen cross-links IgE on the cell surface
what cytokines induce class-switching to IgE during type I HSR
IL-4 and IL-13
source of IL-4 for IgE class switching in type I HSR
*derived initially from NK1.1 T cells
*subsequently derived by activated Th2 cells and mast cells
source of IL-13 for IgE class switching in type I HSR
produced by Th2 cells and mast cells
important cytokines released by mast cells
IL-3, IL-5, and GM-CSF
*promote eosinophil production and activation
IL-5 effects upon release from mast cells during type I HSR
*stimulates the production of EOSINOPHILS in the bone marrow
*promotes EOSINOPHIL ACTIVATION
*can help with diagnosis
eosinophil cationic protein
*toxic to parasites
*neurotoxin
atopy
*condition exhibited by allergic individuals
*atopic individuals exhibit higher than normal levels of circulating IgE and eosinophils
*linked to several genetic loci, including CYTOKINE GENES and HLA CLASS II ALLELES
early phase effects of degranulation in type I HSRs
*depends on WHERE you have these cells
1. GI tract: expulsion of GI contents (diarrhea and vomiting)
2. airways: congestion and blockage of airways; swelling and mucus secretion in nasal passages
3. blood vessels: increased fluid in tissues, etc
immediate (early) phase response in type I HSRs
*production of prostaglandins, leukotrienes, platelet activating factors, histamine, TNF alpha, and IL-5 results in RECRUITMENT AND ACTIVATION OF Th2 CELLS, EOSINOPHILS, BASOPHILS, and NEUTROPHILS
late phase response in type I HSRs
*occurs 8-12 hours AFTER immediate response
*mast cells and basophils release cytokines that PROMOTE cellular INFLAMMATION
treatment of asthma (a type I HSR)
- reducing the effects of inflammatory modulators (inhaled corticosteroids or beta-2 agonists)
- reduce antigen intolerance (allergy shots to introduce increased doses of allergen)
- monoclonal antibodies (anti-IgE mab, anti-IL-4 mab, anti-TNF alpha mab)
normal flora, Tregs, and type I HSRs
*hypothesis that the changes in microflora over the past few decades, induced by increased use of antibiotics, has lead to an increase in incidence of allergic diseases
*normal microbiota may promote ACTIVATION OF Tregs in the GI tract
regulatory T cells
*CD4+, CD25+, FOXP3+ T cells
*arise in the thymus
*activated by dendritic cells
*function to SUPPRESS THE IMMUNE SYSTEM by releasing TGF-beta and IL-10 (inhibit CD4 and CD8 effector functions)
syndrome associated with FOXP3 deficiency
IPEX syndrome
*due to lacking Tregs
type II HSRs - overview
antibodies bind to cell surface antigens and cause:
1. cellular destruction: cell is opsonized, leading to phagocytosis, complement activation, and/or NK cell killing
2. inflammation - binding of antibodies causes complement activation and Fc-mediated inflammation
3. cellular dysfunction - antibodies bind to cellular receptors, leading to abnormal blockades or activation of downstream processes
NK cell killing in type II HSRs
*IgG produced against self-antigen and binds the cell
*IgG also binds to Fc receptor on NK cell
*NK cell releases PERFORINS and GRANZYMES, leading to cell destruction
hemolytic anemia of a newborn (a type II HSR)
*Rh NEGATIVE MOM carries Rh-positive fetus
*during first delivery, fetal RBCs enter maternal circulation, resulting in SENSITIZATION (mom makes antibodies against baby’s Rh)
*in a subsequent pregnancy, anti-Rh antibodies (IgG) cross the placenta, resulting fetal damage/death
prevention of hemolytic anemia of newborn
give mom anti-Rh IgG (Rhogam) at time of first delivery; prevents mom from making her OWN antibody against Rh
type III HSRs - components
IMMUNE COMPLEX:
1. antigen and antibody (IgG) interact and activate complement
2. complement activation attracts neutrophils
3. neutrophils release lysosomal enzymes, which cause cellular damage
type III HSRs - locations
- if complexes are retained locally, then the damage is also local (arthus reaction)
- if immune complexes can circulate, then systemic, multi-organ effects occur (glomerulonephritis)
arthus reaction (type III HSR)
a local, IMMEDIATE type III HSR at the site of injection
*results in local inflammation, edema and/or necrosis
serum sickness (type III HSR)
DELAYED type III HSR due to antibodies against foreign proteins:
1. antibodies are produced against proteins in the week following an injection/infusion
2. eventually, immune complexes deposit in membranes throughout the body, where they fix complement
3. RESULT = systemic symptoms appearing 5-10 days post-infusion: fever, urticaria, arthralgia, proteinuria, and lymphadenopathy
type IV HSRs - 2 types:
- direct T-cell cytotoxicity (CD8 cells)
- delayed-type hypersensitivity (CD4 cells)
*BOTH generally occur 24-72 hours after antigen exposure
type IV HSR - direct T-cell cytotoxicity
*CD8 + T cells DIRECTLY KILL targeted cells
type IV HSR - delayed-type hypersensitivity
*sensitized CD4+ T cells encounter antigen and release cytokines; resulting inflammation and activation of macrophages results in death of targeted cells
type IV HSR - the 4 Ts
- T-cells
- transplant rejections
- TB skin tests
- touching (contact dermatitis)
type IV HSRs - examples
*type I diabetes
*TB skin test
*contact dermatitis (poison ivy)
*graft-versus-host disease
selective IgA deficiency
*most common primary immunodeficiency
*most patients are asymptomatic
*can present with AIRWAY infections, ATOPY, AUTOIMMUNE DISEASE, and ANAPHYLAXIS to IgA-containing products
*susceptible to Giardiasis in particular
