Diseases of the Immune System III Flashcards
1
Q
self-tolerance
A
normal state of non-responsiveness to ones own antigens
2
Q
requirements for autoimmunity
A
1 immune specific reaction to autoantigen
2 evidence it is not due to tissue damage
3 absence of another cause
3
Q
type I DM
A
autoreactive T cells and antibodies - against pancreatic beta cells
4
Q
multiple sclerosis
A
autoreactive T cells against CNS myelin
5
Q
goodpasture syndrome
A
autoreactive antibodies against BM of lung and kidney
6
Q
SLE
A
autoreactive antibodies against DNA, platelets, RBCs, protein phospholipid complexes
7
Q
central tolerance
A
T and B cells in central lymph organs
T cells - negative selection in thymus
-AIRE - stimulates expression of self-antigens in thymus
B cells - receptor editing in bone marrow
8
Q
peripheral tolerance
A
T and B cells in peripheral tissues
anergy, T-reg cell suppression, deletion
9
Q
anergy
A
T cells - don’t get costimulator CD28
- lose ability to signal
- also express CTLA-4 and PD-1
- inhibitory signals
B cells - don’t get T cell help
-become unable to respond
10
Q
CTLA-4 and PD-1
A
inhibitory signal to T cell activity
-knocked out of this gene - autoimmunity
11
Q
CD28
A
costimulator for T cell activation
12
Q
suppression by T-reg cells
A
CD4 T cells with CD25 and FoxP3
-develop in thymus in response to self antigen
13
Q
Foxp3
A
on T-reg cells
-mutation - autoimmune disease
IPEX
14
Q
CD25
A
on T-reg cells
-polymorphisms - MS and other autoimmunities
15
Q
deletion by activation induced cell death
A
CD4 T cells that recognize self antigen - apoptosis
- proapoptotic Bim - mito patway
- also Fas-FasL death receptor pathway
16
Q
FAS
A
mutation - autoimmune lymphoproliferative syndrome
17
Q
immune-privileged sites
A
antigens hidden from immune syndrome
-testis, eyes, brain
released with trauma - elicit immune response
post-traumatic orchitis and uveitis
18
Q
mechanisms of autoimmunity
A
genes and environmental triggers
19
Q
AIRE
A
expression of self-antigens in thymus
-aid with central tolerance
20
Q
PTPN-22
A
genetic association with autoimmunity
- rheumatoid arthritis, type I DM
- inability to control tyrosine kinase
- excessive lymphocyte activation
21
Q
NOD-2
A
genetic association with autoimmunity
- crohns disease
- cytoplasm sensor for microbes
22
Q
B cell negative feedback
A
Fc receptor for IgG antibodies
-switches off antibody production
23
Q
infection and autoimmunity
A
may upregulate costimulators on APCs
also, some microbes may have antigens that are similar to self-antigens (molecular mimicry)
24
Q
molecular mimicry
A
rheumatic heart disease
-streptococcal proteins similar to myocardial proteins
25
general features of autoimmunity
progressive
| Th1 - M0 / Th17 - neutrophils and monocytes
26
systemic lupus erythematous
SLE
- autoantibodies
- injury to skin, joints, kidney, serosa, etc.
predominantly in woman of childbearing age
usually arises in 20s or 30s
27
autoantibodies in SLE
diverse
- ANAs - antinuclear antibodies
- against DNA, histones, non-histones bound to RNA, nucleolar antigens
-also - to blood cells
-antiphospholipid
-
28
patterns of nuclear fluorescence
1 - homogenous diffuse nuclear staining
2 - peripheral staining
3 - speckled pattern
4 - nucleolar pattern
29
homogenous diffuse nuclear staining
chromatin/histones
30
peripheral staining
double strand DNA
31
speckled pattern staining
non-DNA nuclear constituents
32
nucleolar pattern staining
RNA
| -systemic sclerosis
33
criteria for SLE
must meet 4 of 11
- malar rash - butterfly rash on cheeks
- discoid rash
- photosensitivity
- oral ulcer
- arthritis
- serositis (pleuritis / pericarditis)
- renal disorder
- neuro disorder
- hematologic disorder
- immuno disorder
- antinuclear antibodies
34
diagnostic for SLE
autoantibodies to smith antigen and double strand DNA
35
false positive for syphilis
SLE patients
| -autoantibody for beta-2 glycoprotein complex also binds cardiolipin (in syphilis test)
36
antiphospholipid antibodies
in 40-50% SLE patients
-epitopes of plasma proteins revealed when proteins in complex with phospholipids
```
lupus anticoagulant (in vitro)
-however, individuals in hypercoagulable state**
```
results in secondary antiphospholipid antibody syndrome
37
genetics of SLE
defect in B cell tolerance
| also, deficiency in complement components favoring tissue deposition
38
UV light
exacerbates SLE
39
sex hormones
influence on SLE
40
drugs that induce SLE response
hydralazine
procainamide
D-penicillamine
41
tissue injury in SLE
type III - antibody-mediated
| type IV - immune complex mediated
42
LE cell
any phagocytic leukocyte that has engulfed the denatured nucleus of injured cell
-seen in SLE
43
characteristic lesions in SLE
blood vessels, kidneys, CT, skin
44
blood vessels and SLE
fibrinoid depositi in walls
45
kidney and SLE
lupus nephritis
| -immune complexes in glomeruli
46
5 patterns of lupus nephritis
```
class 1 - minimal mesangial
class 2 - mesangial proliferative
class 3 - focal proliferative
class 4 - diffuse proliferative
class 5 - membranous
```
47
mesangial lupus glomerulonephritis
no or slight (class 1) or moderate (class 2) mesangial proliferation with deposits of Ig and complement
no involvement of capillaries
48
focal proliferative glomerulonephritis
class 3
fewer than 50% involvement of glomeruli
-crescent formation, fibrinoid necrosis, endothelial/mesangial proliferation
-hematuria/proteinuria
49
diffuse proliferative glomerulonephritis
class 4
greater than 50% involvement of glomeruli
-crescent formation, fibrinoid necrosis, endothelial/mesangial proliferation
-hematuria/proteinuria
50
membranous glomerulonephritis
```
class 5
thickened capillary walls
```
severe proteinuria and nephrotic syndrome
51
subepithelial deposits of antibody/complement in glomeruli
membranous glomerulonephritis
between BM and visceral epithelial cells
52
subendothelial deposits of antibody/complement in glomeruli
proliferative glomerulinephritis
-wire loops
between endothelium and BM
53
wire loops
subendothelial deposits create thickened capillary wall
54
skin and SLE
facial malar area - butterfly
also bullae, urticaria, ulcerations, maculopapular lesions
worsened with UV exposure
deposition of Ig and complement
55
joints and SLE
nonerosive synovitis
56
CNS and SLE
antibodies against synaptic membrane
57
serosa and SLE
acute - fibrous exudate on surface
| later - thickened, opaque and fibrous
58
cardiovascular and SLE
non-bacterial verrucous endocarditis
- affects valves
- 1-3mm warty deposits on any heart valve
59
infective endocarditis
larger deposits than SLE
60
spleen and SLE
splenomegaly
capsular thickening
follicular hyperplasia
61
lungs and SLE
pleuritis and pleural effusion
62
clinical features of SLE
typically young woman
- butterfly rash on face, fever, pain in joints
- photosensitivity
- ANAs found
- anemia / thrombocytopenia
- mental aberrations
- CAD
63
course of SLE
rare/acute - die within weeks
-with therapy - flare ups and remission
- during flare-up - hypocomplementemia
- Tx - corticosteroids (immunosuppressant)
common cause of death - renal failure
64
chronic discoid lupus erythematous
skin manifestations of SLE - but no systemic problems
skin plaques - face and scalp
positive ANA test
rarely have double strand DNA antibodies
65
subacute cutaneous lupus erythematous
predominant skin involvement
-widespread and nonscarring
mild systemic symptoms
antibodies to SS-A
HLA-DR3 genotype
66
drug-induced lupus erythematous
hydralazine, procanamide, isonaizid, d-penicillamine
-development of ANAs
renal and CNS involvement are rare
lots of antibodies for histones
HLA-DR4 genotype
67
rheumatoid arthritis
chronic inflammatory
-affects joints
-also skin, vessels, lungs, heart
-
68
sjogren syndrome
keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth)
destruction of salivary and lacrimal glands
autoantibodies against SS-A and SS-B
-both are ribonucleoprotein antigens
often associated rheumatoid arthritis
69
sicca syndrome
decreased saliva
70
rheumatoid factor
antibody against IgG
71
lymphoma vs. intense reactive chronic inflammation
look at clonality of cells present
- monoclonal - lymphoma
- polyclonal - inflammation
72
clinical features of sjogren syndrome
women aged 50-60
keratoconjunctivitis - causes blurry vision, burning, itching
xerostmia - difficulty swallowing food, decreased taste, cracks in mouth
parotid gland enlargement
rare - glomerular lesions
-but do see phosphaturia, uricosuria, renal tubular acidosis
73
mikulicz syndrome
combination of lacrimal and salivary gland inflammation
74
diagnosis of sjogren syndrome
Bx of lip - minor salivary glands
75
node in sjogren
initially T and B cells
tendency to more B cells
can lead to marginal zone lymphoma (B cell malignancy)
76
systemic sclerosis
chronic inflammation
widespread damage to small vessels
progressive interstitial and perivascular fibrosis in skin
excessive fibrosis throughout body
77
slceroderma
aka systemic sclerosis
78
diffuse scleroderma
widespread skin involvement at onset and progression to visceral involvement early
79
limited scleroderma
skin involvement only fingers, forearms, face
-visceral involvement late
some patients develop CREST
80
CREST syndrome
associated with limited scleroderma
calcinosis - deposits in soft tissue
raynauds phenomenon - reduced color in digits/toes
esophageal dysmotility - difficulty swallowing
sclerodactylyl - local thickening of skin of digits/toes
tenalgiectasia - blood vessels near surface of skin
81
pathology of scleroderma
CD4 T cell response to antigen in skin
ANAs - against DNA topoisomerase I (pulmonary fibrosis) and anticentromere antibody (CREST)
82
marfan syndrome
mutation of fibrillin I gene
83
skin and scleroderma
begins in fingers goes centrally
-edema and perivascular infiltrates with CD4 cells
fibrosis of dermis
-subQ calcifications
clawlike hands
84
alimentary tract and scleroderma
fibrosis of muscles in esophagus
GERD can occur
85
lungs and scleroderma
pulmonary HTN and interstitial fibrosis
86
clinical features of scleroderma
50-60 year old
-more likely female
skin thickening, raynauds phenomenon, dysphagia, respiratory difficulty
CREST - in limited scleroderma
-pts with CREST usually have limited involvement of skin - only fingers, forearms, face
87
inflammatory myopathies
inflammation of skeletal muscles
dermatomyositis
polymyositis
inclusion-body myositis
88
mixed CT disease
mix of SLE, systemic sclerosis, and polymyositis
ANAs to U1 ribonucleoprotein
89
polyarteritis nodosa
necrotizing inflammation of vessels
