Chapter 12: Hypersensitivity and Autoimmune Disease Flashcards
(100 cards)
1
Q
What are the 2 principal factors which determine the clinical and pathologic consequences of an HSR or autoimmune disease?
A
- type of immune response
- nature and location of the inciting antigen
2
Q
Type I HSR other name?
A
Immediate HSR
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
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
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
6
Q
What is the immune mechanism of Type II HSR?
A
IgM and IgG against surface (cell surface or extracellular matrix)
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
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
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
10
Q
What is another name for Type II HSR?
A
antibody-mediated
11
Q
What is another name for Type III HSR?
A
Immune complex mediated
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
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
14
Q
What are some stored or released mast cell mediators?
A
- histamine
- heparin
- eosinophil chemotactic factor A (multiple chemokines)
15
Q
What are the effects of histamine?
A
smooth muscle contraction; increased vascular permeability
16
Q
What are the effects of heparin?
A
anticoagulant
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
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
19
Q
What are the effects of leukotrienes C4, D4, E4 (lipoxygenase pathway)?
A
increased smooth muscle contraction and vascular permeability
20
Q
What are the effects of the leukotriene B4 release as a mast cell mediator?
A
chemotactic for neutrophils
21
Q
Allergic rhinitis other name?
A
hay fever
22
Q
Some allergens that can cause allergic rhinitis?
A
trees, grasses, dust, cats, dogs, mites
23
Q
Clinical findings of allergic rhinitis?
A
edema, irritation, mucus in nasal mucosa
24
Q
Allergens in systemic anaphylaxis?
A
insect stings, drug reactions
25
What are the clinical findings in systemic anaphylaxis
bronchial and tracheal constriction, complete vasodilation and death
26
What are some allergens associated with food allergies?
milk, eggs, fish, cereals, grains
27
What are some clinical findings associated with those with food allergies?
hives and GI problems
28
What are some allergens associated with wheal and flare?
in vivo skin testing for allergies
29
What are the clinical findings for wheal and flare?
local skin edema, reddening, vasodilation of vessels
30
What are the allergens associated with asthma?
inhaled materials
31
What are the clinical findings associated with asthma?
bronchial and tracheal constriction, edema, mucus production, massive inflammation
32
List some type II HSR Diseases? (Cytotoxic)
* autoimmune hemolytic anemia (HDNB)
* acute rheumatic fever
* goodpasture syndrome
* transfusion reaction
* autoimmune thrombocytopenic purpura
33
List some non-cytotoxic type II HSR?
* myasthenia gravis
* graves disease
* Type II (insulin-resistant) diabetes
* pernicious anemia
34
What is the target ag in HDNB?
RBC membrane proteins (Rh, I Ags)
35
Mechanism of pathogenesis of autoimmune hemolytic anemia?
opsonization, phagocyotosis, and complement-mediated destruction of RBCs
36
Clinical manifestations of HDNB?
hemolysis, anemia
37
What is the target ag involved in acute rheumatic fever?
streptococcal cell-wall Ag; Ab cross-reacts with myocardial Ag
38
What is the mechanism of pathogenesis of acute rheumatic fever?
inflammation, macrophage activation
39
Clinical manifestation of acute rheumatic fever?
myocarditis, arthritis
40
What is the target ag involved in Goodpasture syndrome?
Type IV collagen in basement membranes of kidney glomeruli and lung alveoli
41
What is the mechanism of pathogenesis of Goodpastures?
complement and Fc- receptor mediated inflammation
42
What are clinical manifestations of Goodpasture syndrome?
nephritis, lung hemorrhage, linear Ab deposits
43
What is the target ag in a Type II HSR caused by transfusion reactions?
ABO blood glycoproteins
44
Mechanism of pathogenesis of transfusion reactions?
IgM isohemagglutinins formed naturally in response to normal bacterial flora cause opsonization + complement activation
45
What are the clinical manifestations of transfusion reactions?
hemolysis
46
What is the target ag in autoimmune thrombocyotopenic purpura?
platelet membrane proteins
47
What is the mechanism of pathogenesis of autoimmune thrombocytopenic purpura?
Ab-mediated platelet destruction through opsonization and complement activation
48
What are the clinical manifestations of autoimmune thromocytopenic purpura?
bleeding
49
What is the target ag in myasthenia gravis?
acetylcholine receptor
50
What is the mechanism of pathogenesis of myasthenia gravis?
Ab inhibits acetylcholine binding, downmodulates receptors
51
Clinical manifestations of myasthenia gravis?
muscle weakness, paralysis
52
What is the target ag in Graves disease?
TSH receptor
53
What is the mechanism of pathogenesis involved in graves disease?
ab-mediated stimulation of TSH receptors
54
What is the clinical manifestation of graves disease?
hyperthyroidism followed by hypothyroidism
55
What is the target ag involved in type II (insulin-resistant) diabetes?
insulin receptor
56
What is the mechanism of pathogenesis of Type II (insulin-resistant) diabetes?
Ab inhibits binding of insulin
57
What are the clinical manifestation of Type II (insulin-resistant) diabetes?
hyperglycemia
58
What are the target antigens involved in pernicious anemia?
intrinsic factor of gastric parietal cells
59
What is the mechanism of pathogenesis involved with pernicious anemia?
neutralization of intrinsic factor, decreased absorption of vitamin B12
60
What are the clinical manifestation of pernicious anemia?
abnormal erythropoiesis, anemia
61
List some Type III Hypersensitivities.
* Systemic lupus erythematosus
* poststreptococcal glomerulonephritis
* arthus reaction
* serum sickness
* polyarteriris nodosa
62
What is the target ag involved in systemic lupus erythematosus?
dsDNA, Sm, other nucleo-proteins
63
What are the clinical manifestations of systemic lupus erythematosus?
nephritis, arthritis, vasculitis, butterfly facial rash
64
What is the antigen involved in poststreptococcal glomerulonephritis?
streptococcal cell wall ags (may be "planted" in glomerular basement membrane)
65
What are the clinical manifestations of poststrep glomerulonephritis?
nephritis, "lumpy-bumpy" deposits
66
What is the ag involved in arthus reactions?
any injected protein
67
What are the clinical manifestations of arthus reactions?
local pain and edema
68
What are the ag involved in serum sickness?
various proteins
69
What are the clinical manifestations of serum sickness?
arthritis, vasculitis, nephritis
70
What is the antigen involved in polyarteritis nodosa?
Hep B virus Ag
71
What is the clinical manifesation of polyarteritis nodosa?
systemic vasculitis
72
List some Type IV hypersensitivity conditions.
* tuberculin test
* contact dermatitis
* Hashimoto thyroiditis
* MS
* RA
* Insulin- dependent diabetes mellitus (type I)
* Guillan Barre syndrome
* celiac disease
* crohn disease
73
What is the specificity of pathogenic T cells in regards to tuberculin tests?
PPD (tuberclin and mycolic acid)
74
What is the specificity of pathogenic T cells in regards to contact dermatitis?
nickel, poison ivy/oak catechols, hapten/carrier
75
What is the specificity of pathogenic T cells in regards to Hashimoto thyroiditis?
Unkown Ag in thyroid
76
What is the specificity of pathogenic T cells in regards to MS?
myelin basic protein
77
What is the specificity of pathogenic T cells in regards to RA?
Unknown Ag in joint synovium (type II collagen?)
78
What is the specificity of pathogenic T cells in regards to insulin-dependent diabetes mellitus (type I)?
islet-cell antigens, insulin, glutamic acid decarboxylase, others
79
What is the specificity of pathogenic T cells in regards to Guillain-Barre syndrome?
peripheral nerve myelin or gangliosides
80
What is the specificity of pathogenic T cells in regards to celiac disease?
CD4+ cells- gliadin, CD8+ cells _ HLA class I like molecule expressed during stress
81
What is the specificity of pathogenic T cells in regards to Crohn disease?
unknown Ag, commensal bacteria?
82
What are some disease classified as type IV pathologies in which autoantibodies are present and used as clinical markers?
Hashimotos and RA
83
What are the clinical manifestations of tuberculin test?
indurated skin lesion (granuloma)
84
Clinical manifestation of contact dermatitis?
vesicular skin lesions, pruritus, rash
85
Clinical manifestations of Hashimoto thyroiditis?
hypothyroidism
86
Clinical manifestations of MS?
progressive demyelination, blurred vision, paralysis
87
Clinical manifestation of RA?
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
Clinical manifestation of insulin-dependent diabetes mellitus (type I)?
chronic inflammation and destruction of β cells, polydipsia, polyuria, polyphagia, ketoacidosis
89
Clinical manifestation of Guillain-Barre syndrome?
Ascending paralysis, peripheral nerve demyelination
90
Clinical manifestation of celiac disease?
Gluten sensitive enteropathy
91
Clinical manifestation of Crohn disease?
chronic intestinal inflammation due to Th1 and Th17 cells, obstruction
92
HLA allele associated with RA?
DR4
93
HLA allele associated with Insulin-dependent diabetes mellitus?
DR3/DR4
94
HLA allele associated with MS?
DR2
95
HLA allele associated with Goodpasture's?
DR2
96
HLA allele associated with systemic lupus erythematosus?
DR2/DR3
97
Name conditions associated with the B27 HLA allele.
Ankylosing spondylitis, psoriasis, inflammatory bowel disease, reactive arthritis
98
What are the HLA alleles associated with celiac disease?
DQ2 or DQ8
99
What are the HLA alleles associated with Graves disease?
B8
100
What are other autoimmune disease correlated with production of antinuclear antibodies? Name these antibodies for each condition.
* diffuse systemic sclerosis (antibodies to DNA topoisomerase 1)
* limited scleroderma (CREST; antibodies to centromeric proteins)
* Sjogren syndrome ( ab to ribonucleoproteins)
