APPP: L22 Hypersensitivity Reactions

… is an altered immunological response to an antigen that results in disease or damage to host

Hypersensitivity reaction

Hypersensitivity reactions can be classified by the … that cause the disease (Type I-IV) or the … of the antigens

mechanisms, source

What are 3 sources of antigen?

Allergy, autoimmunity, and alloimmunity

… is an over-reactivity to otherwise unharmful environmental antigens or chemcials

Allergy

… is a disturbance of immunological tolerance of self-antigens

Autoimmunity

… is an immunological reaction against tissues of another individual (blood transfusion, organ transplant, fetus during pregnancy)

Alloimmunity

Type I is … mediated and a … allergy

IgE, classic

Type II is … mediated and are … reactions

IgG/IgM, cytotoxic

Type III involves … and includes … diseases

IgG/IgM, immune-complex

Type IV involves … and is a … hypersensitivity

T cell, delayed type

What is the onset of type I: classic allergies?

Minutes

What is the onset of type II: cytotoxic reactions?

Hours to days

What is the onset of type III: immune-complex diseases?

Hours to weeks (1st encounter)

What is the onset of type IV: delayed type hypersensitivities?

2-3 days

Allergies are mediated by IgE attached to … cells

mast

Symptoms resulting from allergic responses are known as …

anaphylaxis

Allergy occurs within minutes of … of allergens

re-exposure

In degranulation:

• Allergen binds …/FceR1 on mast cell surface

• … of two IgE to activate degranulation signal with …

• … influx

• … and release of inflammation mediators 

IgE, Cross-links, tyrosine phosphorylation, Ca2+, degranulation

What are the 2 phases of an allergy response?

Immediate and late

… Phase:

• Release of … and … by mast cells

• Occurs within minutes following exposure to allergens

Immediate, histamine, cytokines

… Phase:

• Induction and continuing synthesis of eicosanoids, cytokines and chemokines

• … cell infiltrate (eosinophils and others)

• … muscle contraction, edema

• May last hours to days, and lead to … inflammatory reaction

Late, Immune, Smooth, chronic

Immediate phase has a … magnitude and a … duration, while late phase has a … magnitude and last …

higher, shorter, lower, longer

What are the 3 mechanisms of an allergic response?

Sensitization, effector stage, and degranulation

… are small 15-40,000 MW substances that can cause an allergic reaction

Allergens

In type I hypersensitivity reactions: localized anaphylaxis, target organs responds to … contact with allergens

direct

Type 1 hypersensitivity reactions: systemic anaphylaxis

• Systemic … and smooth muscle contraction leads to severe …, edema, and … (shock)

• …, arrhythmia, cyanosis, and cardiac arrest can occur

• … is a medical emergency that require immediate medical interventions

• … presentations up to 30% cases

vasodilation, bronchiole constriction, hypotension, tachycardia, anaphylactic shock, biphasic 

… is associated with genetic predisposition for localized anaphylaxis

Atopy

Atopic individuals have higher levels of … and … in their bloodstream

IgE, eosinophils

Candidate polymorphic genes related to atopy include … receptor, … cytokine (promotor region), FceRI (high affinity IgE receptor), … (present peptides promoting Th2 response), and … genes

IL-4, IL-4, class II MHC, inflammation

Type II: cytotoxic hypersensitivity is mediated through the … binding of antibodies (IgG or IgM) to a tissue cell … antigen

inappropriate, surface

Antibody binding direct cellular toxicity of target cells through the … pathway MAC, or by … cell mediated ADCC

classical complement, immune

Examples of Type II Hypersensitivity Reactions include:

• … hemolytic anemia (clinical mistakes in blood transfusions)

• … hemolytic anemia (autoimmune disease)

• … Syndrome (autoimmune reaction following viral infections)

ABO, Auto-immune, Guillain Barre

Special Type II Reactions are associated with cell surface receptors targeting …

antibodies

Type A blood has surface antigen … and anti-… antibodies 

A, B

Type B blood has surface antigen … and anti-.. antibodies

B, A

Type AB blood has surface antigens … and …, and does not have neither anti-… nor anti-… antibodies

A, B, A, B

Type O blood has neither … nor … surface antigens and has both anti-… and anti-… antibodies 

A, B, A, B

Type III hypersensitivity: immune complex disease

1. … (IC) are formed when clusters of antibodies (mostly IgG, but also IgM) interlocked after binding to … (not cell surface) foreign or tissue antigen (self antigen = autoimmune diseases)

2. IC are found in circulation, in bodily fluids or deposited in tissue (ex: glomerular basement membrane)

3. IC are normally rapidly removed through the actions of … cell

4. When IC are not effectively removed, they could become trapped in the local tissues and cause … of phagocytes

5. Activation of the … system is also implicated in tissue injury cause by precipitated/trapped IC

Immune complexes, soluble, phagocytotic, degranulation, complement

What are 3 common immune complex conditions?

Glomerulonephritis following streptococcal infection, rheumatoid arthritis, and systemic lupus erythematosus

… is a type of immune response classified by macrophage APC and T cells activation that results in tissue damage 

Delayed type hypersensitivity 

… can be the result of chronic infection or exposure to antigens

Delayed type hypersensitivity

What are examples of type IV: delayed type hypersensitivity (DTH)?

Contact dermatitis and tuberculin formation in tuberculosis

What are 4 factors that could influence autoimmune disorders?

Genetics, sex, infections in susceptible individuals, and age

What is the hypersensitivity type of Guillain Barre disease?

II

What is the hypersensitivity type of Graves disease?

II

What is the hypersensitivity type of Myasthenia Gravis?

II

What is the hypersensitivity type of rheumatoid arthritis?

III

What is the hypersensitivity type of systemic lupus erythematosus?

III

What is the hypersensitivity type of celiac disease?

IV

What is the hypersensitivity type of multiple sclerosis?

IV

What is the hypersensitivity type of type I diabetes?

IV