Hypersensitivity - Stiener-jones Flashcards
What is hypersensitivity?
Exaggerated or aberrant immune response to antigen resulting in inflammation and tissue damage.
What is Type I hypersensitivity?
Referred to as Allergy, atopy or immediate hypersensitivity.
- occurs mixtures after reexposure to antigen/allergen.
- Rapid IgE and mast cell mediated vascular and smooth muscle reaction that is often followed by inflammation.
- Affects 20% of population.
What is the basic sequence of events with Type I hypersensitivity?
- Initial exposure to antigen and production of IgE = Sensitization.
- Th2 cells secrete IL’s
- Th2 cell Cd40L binds to B cell Cd40 - Binding of IgE Ab to Fc receptor on mast cells
- Cross-linking of bound IgE upon reexposure to allergen.
- Release of mast cell mediators
What are the immediate effects of Type I Hypersensitivity?
Dilation of blood vessels, increased vascular permeability, smooth muscle contraction.
What is the late response of Type I hypersensitivity?
Inflammation
What are the common allergens, Route of entry and response of Systemic anaphylaxis?
Common allergens: Drugs, venoms, peanuts & serum.
Route of entry: Intravenously or oral absorption
Response: Edema, increased vascular permeability, Tracheal occlusion, circulatory collapse, death.
What are the common allergens, Route of entry and response of Acute urticaria?
Common allergens: Animal hair, insect bites, allergy testing
Route of entry: Through skin
Response: Local increase in blood flow and vascular permeability.
What are the common allergens, Route of entry and response of Allergic Rhinitis?
Common allergens: Pollens & dust mite feces
Route of entry: inhalation
Response: Edema & irration of nasal mucosa
What are the common allergens, Route of entry and response of Asthma?
Common allergens: Danders, pollens, dust mite feces
Route of entry: inhalation
Response: Bronchial constriction, increased mucous production and airway inflammation
What are the common allergens, Route of entry and response of Food allergy?
Common allergens: Tree nuts, peanuts, shellfish, milk, eggs, fish.
Route of entry: oral
Response: vomiting, diarrhea, purtisis, urticaria (hives), anaphylaxis.
What are the 2 lipid mediators?
Prostanglandins & Leukotrienes
What are the 2 lipid mediators?
Prostaglandins & Leukotrienes
What do Prostaglandins do?
*Made via cyclooxygenase pathway
VASOCONSTRICTION in the LUNGS or dilation in vascular smooth muscle.
- Cause aggregation or disaggregation of platelets.
What do Leukotrienes do?
- Made in Lipoxygenase pathway
- Powerful inducer of BRONCHOCONSTRICTION, INCREASED VASCULAR PERMEABILITY.
- Refered to as slow reacting substance of anaphylaxis (SRS-A)
What are the 2 lipid mediators of mast cell Degranulation?
Prostaglandins & Leukotrienes
What is the immediate response of Mast Cell Degranulation?
Vasoactive amines (Histamine and serotonin) and proteases. - synthesis and secretions of lipid mediators (prostaglandins and Leukotrienes made from arachidonic acid)
What is the late–phase rxn of Mast cell Degranulation?
- Synthesis and secretion of cytokines and chemokine.
- Infiltration of Eosinophils, monocytes and neutrophils.
What do ITAM’s do?
Activate map kinase
Map kinases are important in the formation of what?
Cytokines
What are the most common signs of asthma?
coughing, wheezing, shortness of breath
What causes the narrowing of airways with asthma?
Inflamed muscle wall.
Treatment strategies for asthma?
- inhaled Corticosteroids (dampen inflammatory response)
- Leukotriene modifiers (block chain of reaction)
- Chromolyn =inhaled; prevents mast cell degranulation
- Theophylline = opens airways.
Treatment strategies for asthma?
- inhaled Corticosteroids (dampen inflammatory response)
- inhaled long acting beta2 agonists = receive inflammation.
- Leukotriene modifiers (block chain of reaction)
- Chromolyn =inhaled; prevents mast cell degranulation
- Theophylline = opens airways.
Intravenous antigen (gets into blood) causes what?
mast cell degranulation = systemic response = systemic anaphylaxis
Low does inhalation of antigen leads to what?
Hay fever symptoms
Low dose inhalation of antigen leads to what?
Hay fever symptoms
Enzymes released from mast cells cause what?
Tissue damgage
Cytokine & Lipid mediators released from mast cells cause what?
inflamation
Cytokine & Lipid mediators released from mast cells cause what?
inflammation
All clinical and pathological features of immediate hypersensitivity reactions are driven by ________.
Mediators produced by mast cells.
The most severe from of immediate hypersensitivity is _____.
Anaphylaxis
What 3 events occur as a result of mast cell activation?
- mast cell degranulation
- Synthesis and secretion of lipid mediators
- Cytokine release
What is Type II hypersensitivity?
Antibodies produced by the immune response that bind to antigens on our own cell surfaces.
- primarily IgG and IgM isotypes.
- Host Ab binds to foreign Antigen on cell surfaces or binds self antigen.
Type II hypersensivity can activate complement resulting in _________.
Membrane attack complex formation.
Type II hypersensivity can activate complement resulting in _________.
Membrane attack complex formation.
*Leads to destruction of cells, inflammation, or interfere with normal cellular function.
What is the Target antigen, Mechanism of disease and clinical/pathological manifestations of Autoimmune hemolytic anemia?
Target antigen: Erythrocyte membrane proteins
Mechanism of disease: opsonization and phagocytosis of erythrocytes.
Clinical manifestations: Hemolysis, anemia
What is the Target antigen, Mechanism of disease and clinical/pathological manifestations of Myasthenia
Target antigen: Acetylcholine receptor
Mechanism of disease: Ab inhibits acetylcholine binding, down modulate receptors.
Clinical manifestations: Muscle weakness, paralysis
What is the Target antigen, Mechanism of disease and clinical/pathological manifestations of
Target antigen: Thyroid stimulating hormone receptor
Mechanism of disease: Ab-mediated stimulation of TSH receptors
Clinical manifestations: Hyperthyroidism
Type II Hypersensitivity is also known as _____.
Cytotoxic Hypersensitivity
What happens in Hemolytic disease of the Newborn?
Maternal Ab’s target fetal RBC’s for destruction.
Type II Hypersensitivity is also known as _____.
Cytotoxic Hypersensitivity
- Hemolytic newborn
- hemolytic anemia
- Blood transaction reaction
- Graves disease
- Myasthenia gravis
What happens in Blood transfusion reactions?
Hose anti-blood group Ab’s target transfused RBC’s fro destruction
What happens in Myasthenia Gravis?
At receptor Ab’s bind to block the Ach receptor
What happens in Graves Disease?
TSH receptor Ab’s stimulate TSH Receptor to over produce TSH.
What happens in Hemolytic anemia?
Auto-Ab’s are produced against self antigens on the surface of RBC’s. This triggers rapid destruction of RBC’s, leading to anemia.
Tx of Hemolytic anemia?
Prednisone or blood transfusion
Tx of Newborn Hemolytic disease?
anti-Rh Ab
Tx of Graves Disease?
radioactive iodine, anti-thyroid drugs or thyroid removal.
Tx of Myasthenia Gravis?
Cholinesterase inhibitors and corticosteroids
Summarize Type II….
Host Ab binds foreign Ag on cell surfaces or binds self Ag.
*IgG
What is Type III Hypersensitivity?
Ag-Ab complexes clump and despot in blood vessels or tissues attracting an acute inflammation response.
What happens to larger aggregates in Type III?
they fix complements and are cleared from circulation by phagocytes.
What do small complexes in Type III do?
deposit in vessels or tissue.
What are examples of Type III?
Systemic lupus, Arthus reaction, serum sickness, lupus nephritis and rheumatoid arthritis.
Type III occurs within ______ after exposure to antigen.
3-10 hours
In Type III, immune complexes trigger inflammation via 3 mechanisms, what are they?
- Mast cell activation
- Macrophage release TNF-Alpha and IL-1 that induce inflammatory cascade.
- C3a, C4a and C5a
The Arthus rx (type III) is triggered in the ____ by _____.
Skin by IgG
What are the symptoms of Arthus?
Swelling, induration, severe pain, edema, hemorrhage, (gangrene in extreme cases)
Tx of arthus?
anti-inflammatory agents
Serum sickness is example of ________.
transient systemic immune complex-mediated syndrome.
What causes serum sickness?
Injection of a foreign protein or proteins which leads to antibody response.
Symptoms of serum sickness?
Fever, chills, rash, nephritis, lymphadenopathy.
_____ is self limiting and follows kinetics of secondary Ab response.
Serum sickness (Type III)
Most severe Type III hypersensitivity disease?
SLE = IgG Ab against ubiquitous self antigen in all nucleated cells.
Damage can lead to death.
Type III summary?
Ag-Ab complexes clump and aggregate in or near blood vessels attracting an acute inflammatory reaction.
- Primarily IgG (possibly IgM or IgE)
- Immune complex
- Ex. arthus, serum sickness & SLE
Tx of lupus?
avoidance or anti-inflammatory agents
Tx of serum sickness?
don’t get shots. (avoid anti-venom, antihistamines, corticosteroids)
Tx of Arthus?
avoidance or anti-inflammatory agents
Tx of lupus?
NSAID, corticosteroids, immunosuppressive agents.
What is Type IV hypersensitivity?
Its a cell mediated reaction, mediated by Ag specific T cells which induce macrophage infiltration in a sensitized individual.
- DTH response to injected ir absorbed Ab
- 2-3 days
- Ex. TB test, contact dermatitis, chronic asthma, crohn’s disease.
Type IV is generally initiated by ____>
Happens (small molecules that must become bound to a larger carrier molecule in order illicit an immune response.
Tb test is example of _______.
Type IV
