Hypersensitvity Flashcards
What is hypersensitivity?
over-reaction of the immune system to harmless environmental antigens
What are the four types of hypersensitivity (I-IV)? What determines the four types of hypersensitvity?
Immediate, antibody mediated (cytotoxic) hypersensivity, immune complex-mediated, delayed (cell-mediated) hypersensitivity
based on location of the target antigen and whether the immune response is based on antibodies or immune cells
It is possible to compare the effector mechanisms of immune response to
humoral and cell-mediated immunity against foreign antigens
Describe Type 1or immediate hypersenstivity.
allergies or atopic disoders
atopic individuals are 10-40% of population and have higher levels of IgE and eosinophils
Clinical manifestations of Type I hypersensitivity are called _____. They depend on____ and ____?
anaphylatic reactions; route of entry of the antigen and location of responding cells
What are some common sources of antigens?
inhaled (pollen, dander, mold), injected: insect venom, vaccines, drugs, therapeutic proteins; ingested (food, orally administered drugs); contacted material (plant leaves industrial products made from plants)
What are the requirements for allergens?
low molecular weight, highly soluble and stable
contain peptides that can be presented MHC class 2
activated TH2 cytokine, esp. IL 4
stimulate IgE repsonse
What do type I responses require? How does this occur?
Initial sensitization to allergen;
first exp to antigen
antigen activation of TH2 cells–> IgE class switchign
production of IgE
binding of IgE to FceRI on mast cells
What are some of the other mechanisms to mast cell degranulation?
IgG cross-linking and C5a binding to complement receptors
What causes mast cell degranulation?
Subsequent exposures to allergen leads to mast cell degranulation
Describe the reaction
reaction has 2 stages: immediate, withinin minutes- wheal (swelling from leakage-histamine effect) and flare (engorged with RBCs)
late phase: more widespread swelling, inflammation
What do mast cell granules contain?
enzymes like tryptase which contribute to tissue remodeling
toxic mediators like histamine. which increase vascular permeability and cause smooth muscle contractions
cytokines especially TNF alpha, promotes inflammation and stimulates other cytokine production
chemokines and lipid activators
What is the role of CCL3?
a chemokine that promotes the influx of monocytes, macrophages, and neutrophils
What are leukotrienes?
cause smooth muscle contraction, increase vascular permeability, and are involved in smooth muscle contraction
Is there a genetic component to developing allergies?
yes, possibly genes involved include MHC and non-MHC (IL-4, IL-4 receptor, IgE receptor)
What is the hygiene hypothesis?
Suggests that the incidence of allergies has doubled over the past 10-15 years, possibly due to better and increased hygiene which has resulted in less exposure to pathogens, skewing to TH2 rather than TH1
What are the treatments of allergies?
avoidance of allergen, use of drugs that reduce the symptoms, desensitization to allergen, allergenic peptide vaccination
Describe Type II: antibody mediated (cytotoxic) hypersensitivity.
reactions occur after antibody is bound to cellular proteins; antibodies are produced because cell proteins have been altered and antibodies initiate the inflammatory response in the tissue
Give an example of Type II hypersensitivity?
hemolytic anemia where production of anti-RBC antibodies results in the destruction of RBCs involved, can be a result of a mishandled blood transfusion
What are some possible autoimmune diseases that result from Type II sensitivity?
when antibodies target cell surface receptors: myasthenia gravis, Grave’s disease, Hashimoto’s throiditis (hypothyroidism), insulin resistant diabetes
Describe Type III hypersensitivity, what is another name for it?
Immune complex mediated hypersensitivity; caused by the deposition of persistent immune complexes of IgG and soluble antigens that are complement fixing, initiates tissue damaging inflammatory responses
name the qualities of the immune complex that determine their pathogenicity
size, isotype, valency, charge, and ability to fix the complement
In immune complex mediated hypersentivity, what determines the clinical manifestation?
site of deposition
What are some sites of deposition for ICs?
Intravenous: vasculitis in blood vessels, nephritis in kidneys, and arthithritis in joints
subcutaneous: arthus reaction in perivascular area
inhaled: farmer’s lung in alveolar/capillary interface
What are some examples of IC mediated hypersensitivity reactions?
arthus reaction, serum sickness, post-streptococcal glomerulonephritis
What is arthus reaction?
localized injected antigen binds to IgG, activates complement, results in localized inflammatory response with increased fluid, protein and cells
What is serum sickness?
response occurs after development of antibodies to a large amount of foreign protein such as anti-venom, mouse monoclonal antibody therapeutics, and streptokinase
What is post-streptococcal glomerulonephritis?
occurs several weeks after group A beta-hemolytic streptococcal infection
Describe Type IV hypersensitivity. What’s another name for it?
Delayed (cell-mediated) hypersensitivity; reactions are mediated by antigen specific effector TH1 cells, initiate inflammatory reactions via the production of cytokines (chemokines, IFN-gamma, TNF-alpha, IL-3, GM-CSF) in response to anigen
When does Type IV hypersensitivity usually occur?
1-3 days after contact with antigen
Gives 3 examples of delayed hypersensitivity
delayed-type hypersensitivity: TB reaction localized swelling, erythema, and cellular infiltrate, in response to tuberculin at site of injection
contact hypersensitivity: poison ivy, includes localized epidermal reaction with erythrema, cellular infiltrate, vesicles, and intraepidermal abscesses
celiac disease: gluten allergy, manifests as villous atrophy in the small bowel due to T cell responses to gliadin
What are the treatments for Types II, III, IV hypersensitivities
avoidance of antigen
reduction of the imoact of the immune response to antigen with SAIDs and NSAIDs
reduction of the immune response in general or specifically
induction of regulation of the response- Regulatory T cells
blocking the effector mechanisms of allergic response- cytokines, costimulatory molecules
How would you reduce the immune response in general? specifically?
steroids, cytoxan; targeting pathogenic B and T cells
Type I is mediated by
IgE
Type II is mediated by
IgG: either cell or matrix associated, or cell surface receptor
Type III is mediated by
IgG
Type IV is mediated by
TH1 cells, TH2 cells, CTL
