Hypersensitivity Flashcards
What is a hypersensitivity reaction?
An overreaction to harmless antigen; usually environmental
What is an allergen?
An antigen that causes overreactions
What is atopy?
The genetic tendency to develop allergic diseases, typically associated with heightened immune responses to common allergens, especially inhaled allergens and food allergens.
How can a chemical, like a drug, be an allergen?
Chemicals can penetrate outer layers of skin and bind covalently and non-specifically to proteins and modify self-proteins
What is the typical T-cell response type generated by hypersensitivity?
Th2
What is Type I hypersensitivity?
IgE mediated hypersensitivity
What is Type II hypersensitivity?
IgG/IgM mediated hypersensitivity
What is Type III hypersensitivity?
Immune complex mediated
What is Type IV hypersensitivity?
Cell mediated hypersensitivity; delayed type hypersensitivity
What type of hypersensitivity is not antibody mediated?
Type IV
What is the general goal of IgE?
To rid the body of large, multicellular organisms (parasites, helminths)
What is the prerequisite for Type I hypersensitivity response?
IgE must be produced upone first exposure to antigen
How many times must a person be exposed to an antigen before a hypersensitivity reactions occurs?
Hypersensitivity rxns occur after second exposure to the antigen
What triggers eosinophilic degranulation in a type I hypersensitivity reaction?
Cross-linking between FceR on eosinophils and IgE antibody on a parasite following a secondary exposure the parasite/antigen triggers degranulation
Which cytokines are used in promotion of a anti-parastic Th2 response?
IL-4, IL-5
What is the hygine hypothesis?
States that children are exposed to fewer, less heavy infections that their parents leading to an underdeveloped, un-educated, less experienced immune system, leading to a greater incidence of allergy
Where is IgE typically most concentrated?
In the tissues
True or False: IgE can bind to FceRI only with antigen bound
False- must be no bound antigen
On what cells are FceRI constiuitively expressed?
Mast cells and basophils and activated eosinophils
What is the relative affinity of IgE for FceRI?
Very high, almost irreversible affinity
Once the primary IgE response subsides, all IgE molecules that did not see antigen bind to FceRI on mostly what cell? WHy this cell?
Mostly to mast cells because they live longer than basophils
What makes up the antigen receptor on mast cells?
FceRI + IgE
True or False: A mast cell/ basophil can have antigen receptors of more than one specificity
True
How does secondary antigen exposure induce degranulation in a type I hypersensitivity response
IgE not complexed with the first encounter of the pathogen bind to FceRI receptors on mast cells, and with secondary exposure the antigen cross-links between the IgE-FceRI and signals degranulation
How does Omalizumab work?
Humanized MOAb specific for the sit on IgE that binds to FceRI, which inhibits binding of IgE to mast cells, prevents cross linking and stops degranulation
What are the two types of mast cells?
Mucosal and connective tissue mast cells
What are the beneficial functions of the mast cells?
Maintain tissue integrity, alert the immune system, facilitate repair of wounds
What are the preformed mediators released by mast cells?
Histamine, enzymes/ metalloproteases, TNF-alpha
What are secondary mediators released by mast cells?
Chemokines, cytokines, eicosinoids (leukotrienes and prostaglandins)
What are the effects elicited by histamine? Through what receptor?
Induces vessel permeability and inflammation, smooth muscle contraction, and secretion of mucus; H1 receptor
True or false: Eosinophils are less toxic than mast cells?
False
What eosinophilically released compound stimulates histamine release?
Major Basic Protein
What cytokine induces the activation/proliferation of eosinophils? What chemokine controls eosinophilic migration?
IL-5; CCL11
How do basophils stimulate a Th2 response?
Secretion of IL-4 and IL-13
How do basophils stimulate B cells to class switch to IgE/ IgG4 producing cells?
Basophils express CD40L
What are the characteristics of allergens?
Low molecular mass, high solubility, and high stability
What is a wheal and a flare in the context of allergy testing?
Clinicians test patient sensitivity by injecting small quantities of antigen into the skin; a wheal is edema at the site of infection, a flare is an area of redness
What type of allergen are eliminated quickest? Longest?
Airborne quickest, blood/ connective tissue longest
What type of allergen causes systemic anaphylaxis?
Blood antigens
What are the possible symptoms of anaphylaxis?
Edema in many tissues, hypotension, irregular heartbeat, loss of consciousness, difficulties swallowing and breathing, stomach cramps and vomiting
What is the most common cause of anaphylactic shock?
Penicillin or related drugs
What is allergic rhinitis?
Caused by inhaled allergens, leading to localized edema and obstruction of nasal airways, histamine release irritates the nose, nasal discharge and fluid-blocked sinuses
What type of hypersensitivity is chronic asthma?
Type IV
What is urticaria?
The wheal and flare reaction— hives or welts
What is angioedema?
Activation of mast cells deeper in the subcutaneous tissue
What is atopic dermatitis?
A more prolonged allergic reaction in the skin causing chronic itching
How are corticosteroids used in treatment of allergic reactions?
Prevent secondary mediators from contributing to the inflammation
How does cromolyn sodium work? IN what medicines is it found?
Prevents degranulation of granulocytes
How does albuterol work?
B- adrenergic receptor agonist
What is the function of metalloproteases?
Breakdown of extracellular matrix proteins
How can a drugs like penicillin lead to a Type II hypersensitivity reaction
The drug can go bad and modify RBC or platelets resulting in hemolytic anemia or thrombocytopenia
What is the time frame of onset for a Type II hypersensitivity reaction?
Within hours
What antibodies are typically involved in a Type II Hypersensitivity reaction?
IgG or IgM
What is the process of a primary response in a hypersensitivity type II reaction?
A patient with bacterial infection has deposition of Cb3 on RBCs as a side effect of infection. When the patient is treated with penicillin it can bind to the RBC surface and form new epitopes, which are recognized by immune cells
What occurs with subsequent exposures to penicillin (or initial drug) with a type II hypersensitivity reaction ?
When treated with the same drug again the antibody specific for the drug modified self-peptides binds to cells and activates complement and recruits macrophages to phagocytosis them or complement deposits on the surface resulting in lysis
What type of hypersensitivity reactions are autoimmune diseases such as myasthenia gravis or type II diabetes?
Type II
What type of hypersensitivity reaction is a incompatible blood transfusion reaction?
Type II
What mediates Type III hypersensitivities?
Small immune complexes that deposit on the walls of blood vessels or alveoli
How do small immune complexes cause problems in type III hypersensitivities?
Immune complexes will accumulate on tissue and then fix complement and initiate inflammatory reactions which leads to tissue damage
What is the typical instigator of type III hypersensitivity reactions?
Antibodies derived from non-human species
Are large or small immune complexes most efficient at eliciting a hypersensitivity III reaction? Why?
Small- large IC aggregations can more easily fix complement and be engulfed and cleared by phagocytes
What is the arthus reaction?
A local, subcutaneous Type III reaction triggered in the skin of sensitized patients
What are the series of events that yield and arthus reaction?
Decomposition of complement on immune complexes, recruitment of immune cells
How does an arthus reaction present?
Erythema and swelling with induration
What is the time frame for onset of the arthus reaction?
4-48 hours after injection
What is serum sickness?
A systemic type III hypersensitivity reaction
What is the time course for the incidence of serum sickness?
Symptoms occur with 7-10 due to deposition of IC in tissues
What antibody mediates serum sickness
High affinity IgG
What are the signs of serum sickness?
Vasculitis, nephritis, arthritis, glomerulonephritis
What are the common instigators of serum sickness?
Drugs (i.e., penicillin), non-humanized monoclonals
What autoimmune diseases cause Type III sensitivities?
Subacute bacterial endocarditis, systemic lupus erythematosus, chronic tissue organ rejection
What mediates Type IV sensitivity reactions?
Antigen- specific T cells
What is the time frame for the onset of Type IV hypersensitivities?
1-3 days after exposure to antigen
What are the two types of damage caused by Type IV hypersensitivity?
CD4+ cell and macrophage- induced damage; CD8+ cytotoxic damage
What type of hypersensitivity requires the most antigen?
Type IV
What is the sensitization of a type IV hypersensitivity reaction?
Antigen is presented to and processed by the APC that migrate to the regional lymph node and activate naive specific T cells
What occurs in the second exposure in a hypersensitivity IV reaction?
Antigen is recognized by few antigen specific T cells activated and they will release cytokines, chemokines, and initiated inflammatory response at site of secondary antigen introduction
What are common items that can cause CD4 mediated contact dermatitis? What is the likely common instigator? How does it present
Coins, jewelry, and metallic objects; nickel; inflammation anywhere the body contacts nickel
What compound in poison ivy/ poison oak is a powerful hapten?
Pentadecatechol
How does a CD8 mediated contact sensitivity reaction happen?
Proteins of skin cells are degraded ad become altered peptides which are presented to CD8 via MHC I; sensitization CD8 T cells attack areas of skin in contact
What is the immune response to in Celiac disease ?
Gluten
How is celiac disease mediated?
CD4+ T cells react with gluten derived peptides in the GALT and activate tissue macrophages, secreting proinflammatory cytokines and causing inflammation in the small intestines
What would be the result of continuous intake of gluten in a patient with celiac disease?
Atrophy of the villi, malabsorption of nutrients, and diarrhea
What is the basis of the tuberculosis test?
A delayed type hypersensitivity reaction to tuberculin inject under the skin
What is the cause of acute rheumatic fever?
Cross reactive antibodies between M protein of strep pyogenes and cardiac tissue
