Immuno - Immune Responses (Hypersensitivity & Blood Transfusion Reactions)

Question 1

What are the types of hypersensitivity? In general, what mediates each?

Answer 1

Type I - Anaphylactic and atopic; Type II - Cytotoxic (antibody mediated); Type III - Immune complex; Type IV - Delayed (T cell-mediated) type; Think: “ACID = Anaphlylatic and Atopic (type I), Cytotoxic (antibody mediated, type II), Immune complex (type III), Delayed (cell mediated, type IV)”

Question 2

Draw a visual depicting what happens in Type I hypersensitivity.

Answer 2

See p. 208-209 in First Aid 2014 or p. 203 in First Aid 2013 for Type I visual

Question 3

What is the mechanism involved in Type I hypersensitivity? What response(s) occur(s)?

Answer 3

Free antigen cross-links IgE on presensitized mast cells and basophils, triggering release of vasoactive amines that act at posctcapillary venules (i.e., histamine).

Question 4

What is the timing of reaction(s) in Type I hypersensitivity, and why?

Answer 4

Reaction develops rapidly after antigen exposure because of preformed antibody. Delayed response follows to production of arachidonic acid metabolites (e.g., leukotrienes)

Question 5

Again, regarding the mechanism of Type I hypersensitivity, which cells and immunoglobulin are involved? What effect does their interaction cause?

Answer 5

Free antigen cross-links IgE on presensitized mast cells and basophils, triggering release of vasoactive amines that act at posctcapillary venules (i.e., histamine).

Question 6

Which type(s) of hypersensitivity is/are antibody mediated?

Answer 6

Types I, II, and III are all antibody mediated.

Question 7

What is the test for Type I hypersensitivity?

Answer 7

Test: skin test for specific IgE

Question 8

What is the overall mechanism involved in Type II hypersensitivity? What effect does this have?

Answer 8

Cytotoxic (antibody mediated) - IgM, IgG bind to fixed antigen on “enemy” cell, leading to cellular destruction; Think: “Type II is cy-2-toxic”

Question 9

What are 3 specific mechanisms involved in Type II hypersensitivity?

Answer 9

3 mechanisms: (1) Opsonization leading to phagocytosis or complement activation (2) Complement-mediated lysis (3) Antibody-dependent cell-mediated cytotoxicity (ADCC), usually due to NK cells or macrophages

Question 10

What is the role of complement in Type II hypersensitivity?

Answer 10

Antibody and complement lead to membrane attack complex (MAC).

Question 11

How is Type II hypersensitivity tested for?

Answer 11

Test: direct and indirect Coombs’

Question 12

Draw a visual depicting the mechanism of Type II hypersensitivity.

Answer 12

See p. 208 in First Aid 2014 or p. 203 in First Aid 2013 for Type II visual

Question 13

What do direct versus indirect Coomb’s tests detect? Give an example of each.

Answer 13

DIRECT: detects antibodies that HAVE adhered to patient’s RBCs (e.g., test an Rh+ infant of an Rh- mother); INDIRECT: detects antibodies that CAN adhere to other RBCs (e.g., test an Rh- woman for Rh+ antibodies)

Question 14

What is the mechanism of Type III hypersensitivity? What effect(s) does it have?

Answer 14

Immune complex - antigen-antibody (IgG) complexes activate complement, which attracts neutrophils; Neutrophils release lysosomal enzymes

Question 15

What type of hypersensitivity is serum sickness? More specifically, what is the mechanism by which serum sickness occurs? How long does it take to happen? What is the result?

Answer 15

An immune complex disease (type III) in which antibodies to the foreign proteins are produced (takes 5 days); Immune complexes form and are deposited in membranes, where they fix complement (leads to tissue damage).

Question 16

Which is the more common Type III hypersensitivity: Serum sickness or Arthus reaction?

Answer 16

Serum sickness is more common than Arthus reaction.

Question 17

What type of hypersensitivity is arthus reaction? More specifically, what is the mechanism by which arthus reaction occurs? What is the result?

Answer 17

Type III hypersensitivity; A local subacute antibody-mediated hypersensitivity (type III) reaction. Intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin.

Question 18

What presentation characterizes Arthus reaction?

Answer 18

Characterized by edema, necrosis, and activation of complement.

Question 19

What is the most common cause of serum sickness?

Answer 19

Most serum sickness is now caused by drugs (not serum) acting as haptens.

Question 20

What presentation characterizes serum sickness?

Answer 20

Fever, urticaria, arthralgias, proteinuria, lymphadenopathy 5-10 days after antigen exposure.

Question 21

What causes the Arthus reaction? What is used to test for it?

Answer 21

Antigen-antibody complexes cause the Arthus reaction; Test: immunofluorescent staining

Question 22

What is the overall mechanism of Type IV hypersensitivity? What effect does it have?

Answer 22

Delayed (T-cell mediated) type - sensitized T lymphocytes encounter antigen and then release lymphokines (leads to macrophage activation; no antibody involved).

Question 23

How can Type IV hypersensitivity be tested?

Answer 23

Test: patch test, PPD

Question 24

Is Type IV hypersensitivity transferable by serum? Why or why not?

Answer 24

Cell mediated; therefore, it is not transferable by serum.

Question 25

What are the 4 T's to associate with Type IV hypersensitivity?

Answer 25

Think: "4th and last"; 4 T's = T lymphocytes, Transplant rejections, TB skin tests, Touching (contact dermititis)

Question 26

What are 2 categories of Type I hypersensitivity disorders? Give at least 2 examples within each category.

Answer 26

(1) Anaphylaxis (e.g., bee sting, some food/drug allergies) (2) Allergic and atopic disorders (e.g., rhinitis, hay fever, eczema, hives, asthma)

Question 27

Describe the presentation of type I hypersensitivity in 3 words (not necessarily symptoms).

Answer 27

Immediate, anaphylactic, atopic

Question 28

What are 9 examples of Type II hypersensitivity?

Answer 28

(1) Autoimmune hemolytic anemia (2) Pernicious anemia (3) Idiopathic thrombocytopenic purpura (4) Erythroblastosis fetalis (5) Acute hemolytic transfusion reactions (6) Rheumatic fever (7) Goodpasture syndrome (8) Bullous pemphigoid (9) Pemphigus vulgaris

Question 29

Describe the presentation of type II hypersensitivity.

Answer 29

Disease tends to be specific to tissue or site where antigen is found

Question 30

What are 5 examples of Type III hypersensitivity?

Answer 30

(1) SLE (2) Polyarteritis nodosa (3) Poststreptococcal glomerulonephritis (4) Serum sickness (5) Arthus reaction (e.g., swelling and inflammation following tetanus vaccine)

Question 31

Describe the presentation of type III hypersensitivity.

Answer 31

Can be associated with vasculitis and systemic manifestations

Question 32

What are 5 examples of Type IV hypersensitivity?

Answer 32

(1) Multiple sclerosis (2) Guillain-Barre syndrome (3) Graft-versus-host disease (4) PPD (test for M. tuberculosis) (5) Contact dermatitis (e.g., poison ivy, nickel allergy)

Question 33

Describe the presentation of type IV hypersensitivity.

Answer 33

Response is delayed and does NOT involve antibodies (vs. types I, II, and III)

Question 34

What is the pathogenesis of allergic reaction? How is it treated?

Answer 34

Type I hypersensitivity reaction against plasma proteins in transfused blood; Treat with antihistamines

Question 35

What is the clinical presentation of allergic reaction?

Answer 35

Urticaria, pruritus, wheezing, fever.

Question 36

What is the pathogenesis of anaphylactic reaction? What is an implication/consequence of this in the context of blood transfusion?

Answer 36

Severe allergic reaction. IgA-deficient individuals must receive blood products that lack IgA.

Question 37

What is the clinical presentation of anaphylactic reaction?

Answer 37

Dyspnea, bronchospasm, hypotension, respiratory arrest, shock.

Question 38

What is the pathogenesis of febrile nonhemolytic transfusion reaction?

Answer 38

Type II hypersensitivity reaction. Host antibodies against donor HLA antigens and leukocytes.

Question 39

What is the clinical presentation of febrile nonhemolytic transfusion reaction?

Answer 39

Fever, headaches, chills, flushing.

Question 40

What is the pathogenesis of acute hemolytic transfusion reaction?

Answer 40

Type II hypersensitivity reaction. Intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host antibody reaction against foreign antigen on donor RBCs).

Question 41

What is the clinical presentation of acute hemolytic transfusion reaction?

Answer 41

Fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinemia (intravascular), jaundice (extravascular hemolysis).