Hypersensitivity Reactions Flashcards
How many types of hypersensitivities?
Four types (ABCD)
Anaphylactic and Atopic (antibody-mediated, type I)
AntiBody-mediated (antibody-mediated, type II)
Immune Complex (antibody-mediated, type III)
Delayed (cell-mediated, type IV)
Which hypersensitivity reaction is antibody-mediated?
Type I, II, III
Which hypersensitivity reaction is cell-mediated?
Type IV
Anaphylaxis (eg, food, drug, or bee sting
allergies) and allergic asthma are which type of hypersensitivity reaction?
Type I hypersensitivity
What are the phases of Type I hypersensitivity?
Immediate (minutes):
antigen crosslinks
preformed IgE on presensitized mast cells → immediate degranulation → release:
-histamine (a vasoactive amine)
-tryptase (marker of mast cell activation)
-leukotrienes
Late (hours):
chemokines (attract inflammatory cells, eg, eosinophils) and other mediators from mast cells → inflammation and tissue damage.
What is the mechanism of type II hypersensitivity?
Antibodies bind to cell-surface antigens causing
→ Cellular destruction
—cell is opsonized (coated) by antibodies, leading to either:
- Phagocytosis and/or activation of complement system
or
- NK cell killing (antibody-dependent cellular
cytotoxicity)
→ Inflammation
—binding of antibodies to cell surfaces → activation of complement system and Fc receptor-mediated inflammation
→ Cellular dysfunction
—antibodies bind to cell surface receptors → abnormal blockade or activation of downstream process.
What is the difference between direct & indirect Coombs test?
Direct Coombs test
—detects antibodies attached directly to the RBC surface
Indirect Coombs test
—detects presence of unbound antibodies in the serum
What are some examples of type II hypersensitivity with cellular destruction?
- Autoimmune hemolytic anemia (including drug induced form)
- Immune thrombocytopenia
- Transfusion reactions
- Hemolytic disease of the newborn
What are some examples of type II hypersensitivity with inflammation?
- Goodpasture syndrome
- Rheumatic fever
- Hyperacute transplant rejection
What are some examples of type II hypersensitivity with cellular dysfunction?
- Myasthenia gravis
- Graves disease
- Pemphigus vulgaris
What is the mechanism of type III hypersensitivity?
In type III reaction, imagine an immune complex as 3 things stuck together:
“antigen-antibody-complement”
Immune complex—antigen-antibody (mostly
IgG) complexes → activate complement → attracts neutrophils which release → lysosomal enzymes.
Can be associated with vasculitis and systemic manifestations.
What is serum sickness?
Which type of hypersensitivity reaction?
Prototypic immunecomplex disease. Antibodies to foreign proteins are produced and 1–2 weeks later, antibody-antigen complexes form and deposit in tissues → complement activation → inflammation and tissue damage (↓ serum C3, C4)
Type III hypersensitivity
What is Arthus reaction?
Example?
Which type of hypersensitivity reaction?
Local subacute immune complex-mediated hypersensitivity reaction.
Intradermal injection of antigen into a presensitized (has circulating IgG) individual leads to immune complex formation in the skin
(eg, enhanced local reaction to a booster vaccination).
Characterized by
- edema
- fibrinoid necrosis
- activation of complement
Type III hypersensitivity
Examples of Type III hypersensitivity?
- SLE
- Rheumatoid arthritis
- Reactive arthritis
- Polyarteritis nodosa
- Poststreptococcal glomerulonephritis
Features of serum sickness?
What are some causes?
- Fever
- urticaria
- arthralgia
- proteinuria
- lymphadenopathy occur 1–2 weeks after antigen exposure
Associated with:
- drugs (may act as haptens, eg, penicillin, monoclonal
antibodies)
- infections (hepatitis B)
What is the mechanism of type IV hypersensitivity?
Two mechanisms, each involving T cells
(cell-mediated):
- Direct cell cytotoxicity: CD8+ cytotoxic T cells kill targeted cells
- Inflammatory reaction: effector CD4+ T cells recognize antigen and release inflammation-inducing cytokines
Response does not involve antibodies (vs types I,
II, and III).
Which hypersensitivity reaction is cell-mediated?
Type IV hypersensitivity
Which hypersensitivity response does not involve antibodies?
Type IV hypersensitivity
Examples of Type IV hypersensitivity?
4T’s: T cells, Transplant rejections, TB skin
tests, Touching (contact dermatitis)
- Contact dermatitis (eg, poison ivy, nickel allergy)
- Graft-versus-host disease
- Tests:
>PPD for TB infection
>patch test for contact dermatitis
>Candida skin test for T cell immune function
What are the types of blood transfusion reactions?
Allergic/ anaphylactic reaction
Acute hemolytic transfusion reaction
Febrile nonhemolytic transfusion reaction
Transfusion related acute lung injury
Delayed hemolytic transfusion reaction
What is pathogenesis of allergic/ anaphylactic reaction?
Type I hypersensitivity reaction against plasma proteins in transfused blood
IgA-deficient individuals should receive blood products without IgA
Which type of blood transfusion reaction occurs within minutes?
Why?
Allergic/ anaphylactic reaction
Within minutes to 2-3 hr
(due to release of preformed inflammatory mediators in degranulating mast cells)
What is clinical presentation of allergic/ anaphylactic reaction?
Allergies:
- urticaria
- pruritus
Anaphylaxis:
- wheezing
- hypotension
- respiratory arrest
- shock
What is pathogenesis of acute hemolytic transfusion reaction?
Type II hypersensitivity reaction
Typically causes intravascular hemolysis (ABO blood group incompatibility)
When does an acute hemolytic transfusion reaction take place?
Why?
During transfusion
or within 24 hr
(due to preformed antibodies)
What is clinical presentation of acute hemolytic transfusion reaction?
- Fever
- hypotension
- tachypnea
- tachycardia
- flank pain
- hemoglobinuria (intravascular)
- jaundice (extravascular)
What is pathogenesis of febrile nonhemolytic transfusion reaction
?
Cytokines created by donor WBCs accumulate during storage of blood products
Reactions prevented by leukoreduction of blood products
When does a febrile nonhemolytic transfusion reaction take place?
Why?
Within 1-6 hr
due to preformed cytokines
Transfusion related acute lung injury mechanism?
Timing?
Symptoms?
Two-hit mechanism:
- Neutrophils are sequestered and primed in pulmonary vasculature due to recipient risk factors
- Neutrophils are activated by a product (eg, antileukocyte antibodies) in the transfused blood and release inflammatory mediators → ↑ capillary permeability → pulmonary edema
Within minutes to 6 hrs
- Respiratory distress
- noncardiogenic pulmonary edema
Delayed hemolytic transfusion reaction mechanism?
Timing?
Why does it have this timing?
Symptoms?
Anamnestic response to a foreign antigen on donor RBCs (Rh [D] or other minor blood group antigens) previously encountered by recipient
Typically causes extravascular hemolysis
Onset over 24 hr
Usually presents within 1-2 wk
(due to slow destruction by reticuloendothelial system)
Generally self limited and clinically silent
- Mild fever
- hyperbilirubinemia
A person with respiratory distress & noncardiogenic pulmonary edema is having which type of reaction?
Transfusion related acute lung injury
A patient presenting with fever, shivering and headache 3 hours after receiving blood transfusion is having which type of reaction?
Febrile nonhemolytic transfusion reaction
