Pathology: Immune Dysfunction - Hypersensitivity Reactions

Front 1

What is another name for type I hypersensitivity disorders?

Back 1

anaphylactic type

Front 2

What is the basic sequence of events in type I hypersensitivity reactions?

Back 2

-antigen stimulates TH2 cells to produce cytokines (IL-4, IL-5), which stimulates B cells to make IgE
-IgE binds to high affinity Fc receptors of basophils and mast cells
-upon 2nd exposure, antigen reacts w/and crosslinks bound IgE
-results in degranulation and release of histamine, production of cytokines, and activation of phospholipase A2

Front 3

What effect do histamine and other vasoactive substances have on the body?

Back 3

cause vasodilation, vascular leakage, and smooth muscle spasm (occurs 5-30mins after exposure)

Front 4

What is the "late-phase" of type I hypersensitivity reactions?

Back 4

2-8days later, recruitment/infiltration of eosinophils, neutrophils, basophils, monocytes; tissue damage

*see tissue and peripheral blood eosinophilia*

Front 5

What are some examples of local type I hypersensitivity reactions?

Back 5

allergic/atopic rxns: seasonal rhinitis (hay fever), allergic asthma, urticaria (hives)

Front 6

What are the symptoms associated with systemic anaphylaxis?

Back 6

(aka anaphylactic shock)
rapid urticaria, bronchospasm, laryngeal edema, and shock

Front 7

What are the "secondary mediators" of an anaphylactic reaction?

Back 7

leukotrienes B4, C4, D4, prostaglandin D2, PAF (all produced from activation of arachidonic acid pathway), and cytokines (to contribute to immune response)

Front 8

What is another name for type II hypersensitivity disorders?

Back 8

cytotoxic, or antibody dependent

Front 9

What is the key characteristic of the antigens in type II hypersensitivity reactions?

Back 9

they are INTRINSIC TO THE CELL OR TISSUE that is damaged (usu either altered or normal cell membrane components)

Front 10

What are the 3 different types of antibody dependent hypersensitivity reactions?

Back 10

1. complement-fixing antibodies
2. antibody-dependent cell-mediated cytotoxicity (ADCC)
3. reaction of anti-receptor antibodies with cell-surface receptors

Front 11

What happens in complement-mediated cytotoxicity?

Back 11

antibody reacts with cell surface antigen, leading to fixation of complement and cell lysis (also opsonizes cells for phagocytosis)

Front 12

What are the common examples of complement-mediated cytotoxicity?

Back 12

-autoimmune hemolytic anemia (develop antibodies against your OWN blood)
-hemolytic transfusion reactions (incompatible ABO)
-erythroblastosis fetalis(rhesus incompatibility)
-Goodpasture syndrome (antibodies against glomerular and pulmonary alveolar basement membranes)

Front 13

What happens in antibody-dependent cell-mediated cytotoxicity (ADCC)?

Back 13

antibody binds to integral cell surface antigen, and cytotoxic leukocytes then react with the Fc portion, which lyse target (usu NK cells, but also monocytes, neutrophils, and eosinophils)

Front 14

What happens in antibody-mediated cellular dysfunction?

Back 14

antibodies form against integral surface receptors that impair or dysregulate fn (w/o causing inflammation or injury)

Front 15

What are the most common forms of antibody-mediated cellular dysfunction?

Back 15

Graves disease -> antibodies stimulate TSH receptor, causing glandular hyperplasia and hyperthyroidism
Myasthenia gravis -> antibodies against ACh receptor in motor end plates cause muscle weakness

Front 16

What is another name for type III hypersensitivity reactions?

Back 16

immune complex mediated reactions

Front 17

What is the key characteristic of the antigen in type III reactions that differs from the antigen in type II reactions?

Back 17

type III: antigen is NOT an intrinsic component of target cells (but can be endogenous or exogenous)
type II: antigen must be intrinsic component of target cells

Front 18

What is the basic mechanism of type III hypersensitivity reactions?

Back 18

1. antigen stimulates antibody production, and antigen-antibody complexes are formed in circulation
2. antigen-Ab complexes get deposited in tissues (vessel walls, serosal surfaces, extravascular sites)
3. initiates inflammatory reaction

Front 19

What are the 3 main components/pathways that contribute to the inflammatory response in type III hypersensitivity reactions?

Back 19

1. complement activation
2. platelet aggregation
3. activation of Hageman factor (XII)

Front 20

What are the downstream effects of complement activation in type III reactions?

Back 20

release anaphylatoxins (C3a/C5a) -> release vasoactive amines -> vasodilation and edema

release chemotactic factors (C5a) -> attracts neutrophils -> phagocytose the complexes -> release lysosomal enzymes -> necrosis

Front 21

What are the downstream effects of platelet aggregation in type III reactions?

Back 21

microthrombi formation -> ischemia -> necrosis

Front 22

What are the downstream effects of the activation of Hageman factor in type III reactions?

Back 22

microthrombi formation -> ischemia -> necrosis

activation of kinins -> vasodilation and edema

Front 23

Why don't these antigen-antibody complexes get removed by mononuclear phagocytotic cells, like normal?

Back 23

smaller immune complexes are less readily removed, sometimes there is overload or dysfn of mononuc phagocytotic system

Front 24

What are some examples of type III hypersensitivity reactions?

Back 24

-serum sickness (react a/g horse serum; systemic deposition complexes esp in heart, joints, kidney)
-systemic lupus erythematosus (also multisystemic)
-arthus reaction (local)
-polyarteritis nodosa (generalized, involving small/medium arteries)
-immune complex-mediated glomerular diseases

Front 25

What is the Arthus reaction?

Back 25

localized area of tissue necrosis from acute immune complex vasculitis; exogenous antigen is introduced (injection or transplant) and reacts w/PREFORMED antibodies

Front 26

What are some different types of immune-complex mediated glomerular diseases?

Back 26

poststreptococcal glomerulonephritis, membranous glomerulonephritis, lupus nephropathy

Front 27

What is another name for type IV hypersensitivity reactions?

Back 27

cell-mediated

Front 28

What are the 2 main types of cell mediated hypersensitivity reactions?

Back 28

delayed-type (mediated by CD4 cells) and CTL-mediated cytotoxicity (mediated by CD8 cells)

Front 29

What is the mechanism in delayed-type hypersensitivity?

Back 29

1st exposure: antigen recognition, results in memory TH1 CD4 cells
re-exposure: memory TH1 cells proliferate and s/c cytokines (e.g. IFN-gamma, IL-2)

Front 30

What is the typical histological appearance of a delayed-type hypersensitivity reaction?

Back 30

proliferation of lymphocytes, monocytes, neutrophils, w/accumulations around small vessels (called "cuffing"), w/induration (hardening) due to fibrin formation

Front 31

What are some examples of delayed-type hypersensitivity reactions?

Back 31

tuberculin reaction, contact dermatitis (from delayed-hypersensitivity or direct chemical injury to skin)

Front 32

What is the mechanism of CTL-mediated cytotoxicity?

Back 32

sensitized CD8 T cells directly kill target cells w/antigen presented by self MHC class I (typically tumor or virus-infected cells)

(kill using perforin or Fas/apoptosis pathway)

Front 33

What happens during hyperacute rejection?

Back 33

antibody-mediated; preformed antibodies react immediately w/donor antigen and localized Arthus reaction follows (acute inflam, fibrinoid necrosis of small vessels, thrombosis)

Front 34

What happens during acute cellular rejection?

Back 34

days to months later; T-cell mediated, w/infiltration of lymphocytes and macrophages; if no arteritis, can respond promptly to immunosuppressants

Front 35

What happens during acute humoral rejection (rejection vasculitis)?

Back 35

antibody-mediated mechanisms cause vascular damage due to deposition of Ig's and complement, w/thrombosis and cortical necrosis

Front 36

What happens during chronic rejection?

Back 36

antibody-mediated vascular damage (vascular fibrointimal prolif), causes tubular atrophy and kidney shrinkage;

occurs months to years later; presents w/rise in serum creatinine over past 4-6mo

Front 37

What is graft vs. host disease?

Back 37

donor's T/B cells react a/g "foreign" host cells; CD8 cells damage directly, CD4 cells recruit macrophages, which damage host

Front 38

In what clinical scenarios is graft vs host disease commonly seen?

Back 38

-bone marrow transplantation (of immunocompetent cells),
-whole blood transfusion in patients with SCID

Front 39

What are the principal target organs of graft-versus-host disease?

Back 39

liver, skin, GI mucosa

Front 40

What are the common presenting sx of graft-versus-host disease?

Back 40

fever, rash, hepatosplenomegaly

Front 41

Which types of sensitivity reactions involve complement?

Back 41

II, III

Front 42

Which types of sensitivity reactions are antibody mediated?

Back 42

I, II, III

Front 43

What are the common manifestations of type IV sensitivity reactions?
**4 T's**

Back 43

T lymphocytes, Transplant rejections, TB skin tests, Touching (contact dermatitis)

Front 44

What is the pneumonic for hypersensitivity reactions I through IV?

Back 44

ACID: Anaphylactic and Atopic (I), Cytotoxic (II), Immune complex (III), Delayed (cell-mediated) (IV)