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Kaplan: Immunology > Chapter 12: Hypersensitivity and Autoimmune Disease > Flashcards

Chapter 12: Hypersensitivity and Autoimmune Disease Flashcards

1
Q

What are the 2 principal factors which determine the clinical and pathologic consequences of an HSR or autoimmune disease?

A
  1. type of immune response
  2. nature and location of the inciting antigen
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2
Q

Type I HSR other name?

A

Immediate HSR

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3
Q

What is the immune mechanism of the Type I HSR?

A

activation of Th2 cells resulting in the production of IgE which in turn bind to the FcεR on mast cells, basophils and eosinophils

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4
Q

Describe the immediate reaction that takes place in a Type I HSR.

A

Degranulation and release of vasoactive amines (ie. histamine) and proteases

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5
Q

Describe the late-phase reaction of HSR type I?

A
  • synthesis and secretion of prostaglandins and leukotrienes
  • cytokine-induced inflammation and leukocyte recruitment
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6
Q

What is the immune mechanism of Type II HSR?

A

IgM and IgG against surface (cell surface or extracellular matrix)

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7
Q

What are the mechanisms of tissue injury in Type II HS reactions?

A
  • Complement mediated (cytotoxic)
    -opsonization and enhanced phagocytosis
    -recruitment and activation of inflammatory cells
  • non-cytotoxic
    -change in physiologic behavior of a cell
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8
Q

What are the immune mechanisms involved in Type III HSR?

A

deposition of immune complexes comprised of IgM or IgG and soluble antigen

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9
Q

What is the mechanism of tissue injury found in Type III HSR?

A

complement-mediated recruitment and activation of inflammatory cells resulting in some combination of arthritis, vasculitis and/or nephritis

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10
Q

What is another name for Type II HSR?

A

antibody-mediated

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11
Q

What is another name for Type III HSR?

A

Immune complex mediated

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12
Q

What is another name for Type IV HSR? Immune Mechanism?

A

Delayed-type Hypersensitivity

inflammatory cytokines, IFN-y and IL-17, produced by CD4+ Th1 and Th17 cells respectively

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13
Q

What are the mechanisms of tissue injury for Type IV HSR?

A
  • Cytokine-mediated tissue damage
    -IFN-y activation of macrophage
    -IL-17 recruitment and activation of neutrophil
  • Direct killing
    -CTL - mediated cellular death
  • CD8+ CTLs (T-cell mediated cytolysis)
    -Direct target cell killing, cytokine-mediated inflammation
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14
Q

What are some stored or released mast cell mediators?

A
  • histamine
  • heparin
  • eosinophil chemotactic factor A (multiple chemokines)
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15
Q

What are the effects of histamine?

A

smooth muscle contraction; increased vascular permeability

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16
Q

What are the effects of heparin?

A

anticoagulant

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17
Q

What are some newly synthesized mediator from arachadonic acid that function as mast cell mediators?

A
  • prostaglandin D2, E2, F2α
  • leukotrienes C4, D4, E4 (lipoxygenase pathway)
  • leukotriene B4
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18
Q

What are the effects of prostaglandin D2, E2, F2α release as a mast cell mediator?

A

increased smooth muscle contraction and vascular permeability

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19
Q

What are the effects of leukotrienes C4, D4, E4 (lipoxygenase pathway)?

A

increased smooth muscle contraction and vascular permeability

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20
Q

What are the effects of the leukotriene B4 release as a mast cell mediator?

A

chemotactic for neutrophils

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21
Q

Allergic rhinitis other name?

A

hay fever

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22
Q

Some allergens that can cause allergic rhinitis?

A

trees, grasses, dust, cats, dogs, mites

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23
Q

Clinical findings of allergic rhinitis?

A

edema, irritation, mucus in nasal mucosa

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24
Q

Allergens in systemic anaphylaxis?

A

insect stings, drug reactions

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25
Q

What are the clinical findings in systemic anaphylaxis

A

bronchial and tracheal constriction, complete vasodilation and death

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26
Q

What are some allergens associated with food allergies?

A

milk, eggs, fish, cereals, grains

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27
Q

What are some clinical findings associated with those with food allergies?

A

hives and GI problems

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28
Q

What are some allergens associated with wheal and flare?

A

in vivo skin testing for allergies

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29
Q

What are the clinical findings for wheal and flare?

A

local skin edema, reddening, vasodilation of vessels

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30
Q

What are the allergens associated with asthma?

A

inhaled materials

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31
Q

What are the clinical findings associated with asthma?

A

bronchial and tracheal constriction, edema, mucus production, massive inflammation

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32
Q

List some type II HSR Diseases? (Cytotoxic)

A
  • autoimmune hemolytic anemia (HDNB)
  • acute rheumatic fever
  • goodpasture syndrome
  • transfusion reaction
  • autoimmune thrombocytopenic purpura
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33
Q

List some non-cytotoxic type II HSR?

A
  • myasthenia gravis
  • graves disease
  • Type II (insulin-resistant) diabetes
  • pernicious anemia
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34
Q

What is the target ag in HDNB?

A

RBC membrane proteins (Rh, I Ags)

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35
Q

Mechanism of pathogenesis of autoimmune hemolytic anemia?

A

opsonization, phagocyotosis, and complement-mediated destruction of RBCs

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36
Q

Clinical manifestations of HDNB?

A

hemolysis, anemia

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37
Q

What is the target ag involved in acute rheumatic fever?

A

streptococcal cell-wall Ag; Ab cross-reacts with myocardial Ag

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38
Q

What is the mechanism of pathogenesis of acute rheumatic fever?

A

inflammation, macrophage activation

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39
Q

Clinical manifestation of acute rheumatic fever?

A

myocarditis, arthritis

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40
Q

What is the target ag involved in Goodpasture syndrome?

A

Type IV collagen in basement membranes of kidney glomeruli and lung alveoli

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41
Q

What is the mechanism of pathogenesis of Goodpastures?

A

complement and Fc- receptor mediated inflammation

42
Q

What are clinical manifestations of Goodpasture syndrome?

A

nephritis, lung hemorrhage, linear Ab deposits

43
Q

What is the target ag in a Type II HSR caused by transfusion reactions?

A

ABO blood glycoproteins

44
Q

Mechanism of pathogenesis of transfusion reactions?

A

IgM isohemagglutinins formed naturally in response to normal bacterial flora cause opsonization + complement activation

45
Q

What are the clinical manifestations of transfusion reactions?

A

hemolysis

46
Q

What is the target ag in autoimmune thrombocyotopenic purpura?

A

platelet membrane proteins

47
Q

What is the mechanism of pathogenesis of autoimmune thrombocytopenic purpura?

A

Ab-mediated platelet destruction through opsonization and complement activation

48
Q

What are the clinical manifestations of autoimmune thromocytopenic purpura?

A

bleeding

49
Q

What is the target ag in myasthenia gravis?

A

acetylcholine receptor

50
Q

What is the mechanism of pathogenesis of myasthenia gravis?

A

Ab inhibits acetylcholine binding, downmodulates receptors

51
Q

Clinical manifestations of myasthenia gravis?

A

muscle weakness, paralysis

52
Q

What is the target ag in Graves disease?

A

TSH receptor

53
Q

What is the mechanism of pathogenesis involved in graves disease?

A

ab-mediated stimulation of TSH receptors

54
Q

What is the clinical manifestation of graves disease?

A

hyperthyroidism followed by hypothyroidism

55
Q

What is the target ag involved in type II (insulin-resistant) diabetes?

A

insulin receptor

56
Q

What is the mechanism of pathogenesis of Type II (insulin-resistant) diabetes?

A

Ab inhibits binding of insulin

57
Q

What are the clinical manifestation of Type II (insulin-resistant) diabetes?

A

hyperglycemia

58
Q

What are the target antigens involved in pernicious anemia?

A

intrinsic factor of gastric parietal cells

59
Q

What is the mechanism of pathogenesis involved with pernicious anemia?

A

neutralization of intrinsic factor, decreased absorption of vitamin B12

60
Q

What are the clinical manifestation of pernicious anemia?

A

abnormal erythropoiesis, anemia

61
Q

List some Type III Hypersensitivities.

A
  • Systemic lupus erythematosus
  • poststreptococcal glomerulonephritis
  • arthus reaction
  • serum sickness
  • polyarteriris nodosa
62
Q

What is the target ag involved in systemic lupus erythematosus?

A

dsDNA, Sm, other nucleo-proteins

63
Q

What are the clinical manifestations of systemic lupus erythematosus?

A

nephritis, arthritis, vasculitis, butterfly facial rash

64
Q

What is the antigen involved in poststreptococcal glomerulonephritis?

A

streptococcal cell wall ags (may be “planted” in glomerular basement membrane)

65
Q

What are the clinical manifestations of poststrep glomerulonephritis?

A

nephritis, “lumpy-bumpy” deposits

66
Q

What is the ag involved in arthus reactions?

A

any injected protein

67
Q

What are the clinical manifestations of arthus reactions?

A

local pain and edema

68
Q

What are the ag involved in serum sickness?

A

various proteins

69
Q

What are the clinical manifestations of serum sickness?

A

arthritis, vasculitis, nephritis

70
Q

What is the antigen involved in polyarteritis nodosa?

A

Hep B virus Ag

71
Q

What is the clinical manifesation of polyarteritis nodosa?

A

systemic vasculitis

72
Q

List some Type IV hypersensitivity conditions.

A
  • tuberculin test
  • contact dermatitis
  • Hashimoto thyroiditis
  • MS
  • RA
  • Insulin- dependent diabetes mellitus (type I)
  • Guillan Barre syndrome
  • celiac disease
  • crohn disease
73
Q

What is the specificity of pathogenic T cells in regards to tuberculin tests?

A

PPD (tuberclin and mycolic acid)

74
Q

What is the specificity of pathogenic T cells in regards to contact dermatitis?

A

nickel, poison ivy/oak catechols, hapten/carrier

75
Q

What is the specificity of pathogenic T cells in regards to Hashimoto thyroiditis?

A

Unkown Ag in thyroid

76
Q

What is the specificity of pathogenic T cells in regards to MS?

A

myelin basic protein

77
Q

What is the specificity of pathogenic T cells in regards to RA?

A

Unknown Ag in joint synovium (type II collagen?)

78
Q

What is the specificity of pathogenic T cells in regards to insulin-dependent diabetes mellitus (type I)?

A

islet-cell antigens, insulin, glutamic acid decarboxylase, others

79
Q

What is the specificity of pathogenic T cells in regards to Guillain-Barre syndrome?

A

peripheral nerve myelin or gangliosides

80
Q

What is the specificity of pathogenic T cells in regards to celiac disease?

A

CD4+ cells- gliadin, CD8+ cells _ HLA class I like molecule expressed during stress

81
Q

What is the specificity of pathogenic T cells in regards to Crohn disease?

A

unknown Ag, commensal bacteria?

82
Q

What are some disease classified as type IV pathologies in which autoantibodies are present and used as clinical markers?

A

Hashimotos and RA

83
Q

What are the clinical manifestations of tuberculin test?

A

indurated skin lesion (granuloma)

84
Q

Clinical manifestation of contact dermatitis?

A

vesicular skin lesions, pruritus, rash

85
Q

Clinical manifestations of Hashimoto thyroiditis?

A

hypothyroidism

86
Q

Clinical manifestations of MS?

A

progressive demyelination, blurred vision, paralysis

87
Q

Clinical manifestation of RA?

A

rheumatoid factor (IgM against Fc region of IgG), alpha-cyclic citrullinated peptide (α- CCP) antibodies, chronic arthritis, inflammation, destruction of articular cartilage and bone

88
Q

Clinical manifestation of insulin-dependent diabetes mellitus (type I)?

A

chronic inflammation and destruction of β cells, polydipsia, polyuria, polyphagia, ketoacidosis

89
Q

Clinical manifestation of Guillain-Barre syndrome?

A

Ascending paralysis, peripheral nerve demyelination

90
Q

Clinical manifestation of celiac disease?

A

Gluten sensitive enteropathy

91
Q

Clinical manifestation of Crohn disease?

A

chronic intestinal inflammation due to Th1 and Th17 cells, obstruction

92
Q

HLA allele associated with RA?

A

DR4

93
Q

HLA allele associated with Insulin-dependent diabetes mellitus?

A

DR3/DR4

94
Q

HLA allele associated with MS?

A

DR2

95
Q

HLA allele associated with Goodpasture’s?

A

DR2

96
Q

HLA allele associated with systemic lupus erythematosus?

A

DR2/DR3

97
Q

Name conditions associated with the B27 HLA allele.

A

Ankylosing spondylitis, psoriasis, inflammatory bowel disease, reactive arthritis

98
Q

What are the HLA alleles associated with celiac disease?

A

DQ2 or DQ8

99
Q

What are the HLA alleles associated with Graves disease?

A

B8

100
Q

What are other autoimmune disease correlated with production of antinuclear antibodies? Name these antibodies for each condition.

A
  • diffuse systemic sclerosis (antibodies to DNA topoisomerase 1)
  • limited scleroderma (CREST; antibodies to centromeric proteins)
  • Sjogren syndrome ( ab to ribonucleoproteins)

Kaplan: Immunology (16 decks)

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