Lecture 13- Type 1 Hypersensitivity Flashcards
What is a hypersensitivity reaction?
When the immune system mechanisms cause damage instead of protection.
How is immune system homeostasis disrupted on its own?
- It may over react to antigens such as with allergies.
- It may under-react as with HIV.
- It may react to self proteins as with autoimmune diseases.
What are the disorders of the immune system?
Allergy, autoimmunity, and immunodeficiency.
Describe hypersensitivity reactions.
Exaggerated, uncontrolled immune responses that are damaging to the host; undesirable side effect of immunity manifesting.
What do hypersensitivities cause?
Trivial discomforts like itching of the skin to potentially fatal diseases like bronchial asthma; diseases include some autoimmune diseases, allograft rejection reactions, various allergic conditions, etc.
What is tissue damage mediated by?
Host effectors’ mechanisms.
What are the general characteristics of type 1 hypersensitivity?
- Immediate hypersensitivity.
- Involve IgE-mediated release of histamine and other mediators from mast cells and basophils.
What are the general characteristics of type 2 hypersensitivity?
- Cytotoxic hypersensitivity.
- Involve IgG or IgM Abs bound to cell surface antigens with subsequent complement fixation.
What are the general characteristics of type 3 hypersensitivity?
- Immune complex-mediated hypersensitivity.
- Involve circulating antigen-antibody immune complexes that deposit in post capillary venules, with subsequent complement fixation.
What are the general characteristics of type 4 hypersensitivity?
- Delayed hypersensitivity.
- Mediated by T cells rather than by Abs.
What are the steps in the process of allergy?
- Sensitization
- Re-exposure to allergen
Describe the sensitization step in the process of allergy.
- Primary exposure to the allergen.
- Occurs when one develops IgE Abs against a substance that is inhaled, ingested, or injected.
- Newly formed IgE Abs stick to basophils and mast cells, but no s/s yet.
Describe the re-exposure step in the process of allergy.
- s/s
- Cellular events for all immediate allergic reactions is the same.
What are the characteristics of type 1 sensitivity?
- Immune reactant: IgE
- Antigen: soluble Ag
- Effector mechanism: mast cell activation
- Example: allergic rhinitis, asthma, systemic anaphylaxis
What are the characteristics of type 2 hypersensitivity?
- Immune reactant: IgG
- Antigen: self Ag
- Effector mechanism: FcR cells (phagocytes, NK cells)
- Example: autoimmune diseases
What are the characteristics of type 3 hypersensitivity?
- Immune reactant: IgG
- Antigen: soluble Ag
- Effector mechanism: FcR cells, complement
- Example: serum sickness, arthus reaction
What are the characteristics of type 4 hypersensitivity?
- Immune reactant: Th1 cells and CTL
- Antigen: soluble Ag and cell-associated antigen
- Effector mechanism: macrophage activation and cytotoxicity
- Example: DTH, contact dermatitis
What is the overall description of type 1 hypersensitivity?
ALLERGY: drug, food, skin, animal, dust
What are allergens?
Antigens that stimulate allergies; non-microbial and mostly proteins; harmless to most individuals but result in allergy in others.
What factors do the development of allergy depend on?
Genetic background: relatives of allergic individuals are more likely to have allergies than unrelated people.
Environment: “hygiene hypothesis” increased hygiene and under-exposure to pathogens.
What is atopy?
IgE mediated hypersensitivity; can be localized or systemic.
Describe localized atopy.
Confined to an organ system, affecting a specific target tissue; asthma, eczema, hay fever.
Describe systemic atopy.
Affects the whole body like anaphylaxis; life threatening reactions such as venom, drugs, or food.
How does an atopic person respond to an allergen?
Produce IgE Abs and show clinical symptoms.
How does a normal person respond to allergens?
No clinical symptoms, eliminate allergen with the help of IgM, IgG, or IgA, but no IgE.
What are the components of the immune system involved in allergy?
- IgE Abs
- Mast cells
- Basophils and eosinophils
- Th2 cells
- IL4, IL5, IL13
What is the sensitization stage of allergy vs the effector stage?
Sensitization: 1st exposure
Effector: 2nd or subsequent exposures.
What is the site of allergen entry?
Taken up by dendritic cells.
What happens after the dendritic cell takes up an allergen?
- Allergen processed by DC and displayed on B cell MHC II.
- Takes it to naive T cell in lymph node.
- T cell proliferates and differentiates to Th2 cell that presents it to B cell.
- B cell activation.
What have high affinity receptors for IgE?
Mast cells; mast cells and basophils become sensitized to the allergen.
What is the effector stage?
If a second exposure to the same allergen occurs when IgE-bound basophils and mast cells are in the body, the effector stage occurs, histamine is released from granules.
What is the study of hypersensitivities called?
Immunopathology.
What is the onset of type 1 hypersensitivity?
Within minutes of antigen challenge.
What are examples of type 1 hypersensitivity?
Allergies to molds, insect bites.
What is the onset of type 2 hypersensitivity?
Within minutes or a few hours of antigen challenge.
What are examples of type 2 hypersensitivity?
Adult hemolytic anemia and drug allergies.
What is the onset of type 3 hypersensitivity?
Usually within 2-6 hours.
What are examples of type 3 hypersensitivity?
Serum sickness and systemic lupus erythematosus.
What is the onset of type 4 hypersensitivity?
Inflammation by 2-6 hours; peaks by 24-48 hours.
What are examples of type 4 hypersensitivity?
Poison ivy and chronic asthma.
Hypersensitivities require a period of _____________.
Sensitization.
What are exceptions to the rule of sensitization requirements for hypersensitivities?
Some blood transfusion reactions and passive transfer of antibody.
What occurs during the sensitization period?
T cells develop, B cells class switch, and plasma cells secrete antibody.
What is anaphylaxis?
Against protection; a serious reaction that is rapid in onset and may cause death. It typically causes a number of symptoms including an itchy rash and throat.
Type 1 hypersensitivity may be __________ or ___________.
Localized, systemic.
What generally is involved in type 1 hypersensitivity?
IgE antibodies and degranulation of mast cells which contain histamine and mediators of anaphylaxis.
Describe the mechanism of type 1 hypersensitivity.
- The first time an allergy prone person runs across an allergen they make large amounts of IgE antibody.
- These IgE molecules attach themselves to mast cells.
- The second time that person has a brush with the same allergen, the IgE primed mast cells release granules and powerful chemical mediators, i.e. histamine and cytokines, into the environment.
- These chemical mediators cause the characteristic symptoms of allergy.
What are the mediators of type 1 hypersensitivity reactions?
- IgE (reaginic Ab)
- Mast cells and basophils (immediate reaction)
- Eosinophil: late phase reaction.
What are the characteristics of inflammation?
Vasodilation and increased vascular permeability.
Give examples of some common allergens.
- Plant pollens: ragweed, ryegrass, birch, etc.
- Foods: milk, shellfish, eggs, peanuts, etc.
- Drugs: penicillin, amoxicillin, etc.
- Insect products: dust mites, bee venom, ant venom, etc.
- Mold spores.
- Animal dander.
What are the causes of mast cell stimulation?
- Physical injury.
- Chemical agent.
- Immunologic process.
What is the result of mast cell stimulation?
Degranulation for the release of histamine, serotonin, and chemotactic factors.
What is the result of the stimulation of mast cells?
Synthesis: construction of leukotrienes and prostaglandins.
What are the proliferation cytokines?
IL-2, IL-4, and IL-5.
What are the differentiation cytokines?
IL-2, IL-4, IL-5, IFN-gamma, and TGF-beta.
What receptor does IgE bind to?
Fc-epsilon.
What are the biologic effects of histamines and lipid mediators?
Vascular leak, bronchoconstriction, and intestinal hypermotility.
What are the biologic effects of cytokines and lipid mediators from activated mast cells?
Inflammation.
What are the biologic effects of enzymes from activated mast cells?
Tissue damage.
When do the late phase reactions of type 1 hypersensitivity occur?
4-6 hours after initial reaction and may last for 24-48 hours.
What are the late phase reactions of type 1 hypersensitivity mediated mostly by?
Eosinophils and various cytokines.
The clinical manifestations of type 1 hypersensitivity depend on what factors?
- Concentration of specific IgE.
- Dose of allergen.
- Route of entry of allergen.
What are the main shock organs of cattle/sheep, horse/cat/pig, and dogs?
- Cattle/sheep: lungs.
- Horse/cat/pig: lungs and intestines.
- Dogs: liver (hepatic veins).
Mast cell degranulation as a result of allergen presentation causes the following anaphylactic symptoms:
- Bronchial smooth muscle contraction: apnea.
- Urticaria.
- Heparin: failure of blood clotting.
- GIT smooth muscle contraction: urination, defecation, bloating.
What are the allergens associated with bee venom?
Phospholipase A2 and hyaluronidase.
What are the symptoms that bee venom causes?
- Drop in blood pressure.
- Hives/itching.
- Swelling of lips, tongue, and larynx.
In what species is allergic inhalant dermatitis common?
Dogs and cats; allergens ingested, inhaled, or absorbed through skin.
What is atopic dermatitis?
Intense pruritis.
What are the symptoms of allergic dermatitis?
Erythema, edema, crusting, scaling, hyperpigmentation, pyoderma, otitis externa, and conjunctivitis.
What are the allergens associated with chronic obstructive pulmonary disease in horses?
Actinomycetes, pollen, mold, etc.
What hypersensitivities is chronic obstructive pulmonary disease in horses mediated by?
Type 1 and type 3.
What are the symptoms of chronic obstructive pulmonary disease in horses?
Exercise intolerance, nasal discharges, chronic cough, labored breathing, etc.
What is the most common clinical presentation of food allergy in dogs/cats?
Nonseasonal pruritis.
What is the defining difference between food allergy and food tolerance?
The presence of regulatory T cells.
What tests are used to diagnose type 1 hypersensitivities?
Intradermal allergy tests and serologic allergy tests.
How does cromolyn sodium inhibit mast cell degranulation?
Prevents Ca influx into mast cells.
How does theophylline inhibit mast cell degranulation?
Inhibits phosphodiesterase and increases intracellular cAMP.
What are antihistamines used for?
Competitive inhibitor of histamine; effective in early phases of anaphylactic reactions but not much benefit for asthma.
What are the mediators of asthma?
Leukotrienes and prostaglandins.
What is the role of epinephrine as a mast cell degranulator?
Bronchodilation: relaxation of bronchial smooth muscles.
Promotes vasoconstriction: increases in blood pressure and CO.
When are corticosteroids beneficial?
Most beneficial when used in late-phase reactions and in chronic allergic disease, but not much of a benefit in immediate phase reactions.
Describe immunotherapy (allergy shots).
- SC administration of allergens that cause high levels of IgG production.
- IgG acts as a blocking antibody that mediates the removal of the allergen before it can bind to IgE.
- May enhance switching to Th1 subset.
