Immunopathology II Flashcards
What is the cause of GVHD?
Recipient’s APC activate CD4 T4 cells, from the graft, causing an immune response
What causes acute GVHD?
Donor cytotoxic T cells or cytokines from helper T cells destroy epithelial cells
What are the skin changes in acute GVHD?
Rash, exfoliation
What are the GIT changes in GHD?
Ulcerative gastroenteritis
What are the hepatic changes in acute GVHD?
Bile duct necrosis
What happens to the immune system in acute GVHD?
Immunosuppression
What are the histological changes in the bile ducts in acute GVHD?
Loss of cuboidal epithelium
Does acute always precede chronic GVHD?
No
What is the MOA of chronic GVHD?
Development of autoreactive T cells from donor stem cells that cannot be clonally deleted
What are the three places that are most often damaged in chronic GVHD?
- Dermis and skin appendages
- GI mucosa
- Jaundice
What are the two, broad types of autoimmune disease?
Systemic
Single cell or organ
Diffuse scleroderma is caused by what?
Topoisomerase I attacked
Limited scleroderma is caused by what?
Centromere proteins acctacked
What are the three criteria for autoimmune disease?
- Immunological rxn to a self antigen
- Reaction is primary o pathogenesis
- No other well defined cause or identifiable etiology
How do you diagnose autoimmune diseases?
Lab tests
Biopsies
clinical characteristics
What happens to antigen naive T cells in the thymus?
Maturation and selection
What are the two things that are necessary to activate a T cell? What happens if these are not present?
B7 from APC, and signals from Th cells
If not present, then anergy
CD28 ligand on T cells bind to what on APCs?
B7
What is peripheral tolerance?
When T cells bind to MHC, but not bind to B7, then they become anergic (or apoptose)
Expression of what genes confers higher susceptibility to loss of self tolerance?
D locus on MHC class I
Polymorphism in what gene that encodes a protein Y-kinase is implicated in autoimmunity?
PTPN-22
How do microbes stimulate autoimmunity?
cross reactivity or molecular mimicry
Which gender is more susceptible to autoimmune disease?
Females
SLE occurs when, and in whom?
Females around 2-3rd decade
What is characteristic of both the butterfly rash, and the discoid rash seen in SLE?
Photosensitive
What is the malar rash in SLE?
fixed erythema, flat or raised over the malar eminences tending to spare the nasolabial folds
What is the discoid rash in SLE?
Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur
What are the neurological disorderes with SLE?
Szs or psychosis
What are the hematologic disorder that occurs in 100% of pts with SLE?
hemolytic anemia
leukopenia
Lymphopenia
What is the serositis in SLE?
Pleuritis or pericarditis document by ST elevation in all leads
What is the renal disorder seen in SLE?
Proteinuira
What are the immunologic disorders with SLE?
Anti-dsDNA, anti SM + anti phospholipid abs
What is the genetic locus associated with SLE? What does this code for?
HLA-DQ
MHC class II
What are the environmental facotors associated with SLE?
UV light
Viruses
Drugs
hormones
What is the immune response to SLE?
Self reactive helper T cells escapse tolerlance drie antibody production by B cells
What type of autoimmunity if SLE?
II, III (antibodies and immune complexes)
What is the immune response to SLE?
Self reactive helper T cells escape tolerance drive autoantibody production by B cells
What are the common symptoms with SLE? (5)
renal disease Arthritis Fever Fatigue weight loss
What causes the autoimmunity of SLE?
Increased burden of apoptotic bodies, thus increased nuclear antigen
What is the hallmark of SLE, and is used in diagnosis?
Antinuclear antibodies (ANA), reflecting a loss of tolerance
What are the 4 categories of Ag that ANAs are directed against in SLE?
DNA
HIstones
Proteins bound to RNA
Nuclear Ag
What is the diagnostic technique used in SLE?
Immunofluorescent staining
What is ANA testing?
Uses human tissue cell culture nuclei as a substrate for diagnostic screening and toerh types of nuclei
What are the two self antigens that are attacked in SLE?
Double stranded DNA
Histones
What is the self antigen attacked in Diffuse scleroderma? Limited?
Diffuse = Topoisomerase I Limited = Centromere proteins
Why can you be totally healthy, but still have reactive self antibodies in your serum?
Damaged tissue is targeted
What is central tolerance?
Destruction of T cells from binding too well to MHC cells in the thymus
What are the three MOA of peripheral tolerance?
- No B7
- Th suppression of self reactive T cells
- Apoptosis
What three bits of information are obtained from ANA testing?
Positive/negative
Titer
Pattern of staining
What does the peripheral rim staining pattern of ANA indicate?
Indicates Ab to ds-DNA
Seen in SLE
Homogenous staining of ANA is found for what three antibodies? Which two disorders is this particularly found in?
Ab to DNP, ds-DNA, histones
Seen in RA and SLE
Speckled ANA staining pattern occurs for what four antibodies?
Anti-sm
Anti-ro and La
anti-Scl 70
Nucleolar ANA staining pattern is found for what antibody?
Anti-centromere
Speckled pattern with anti- Sm and RNP indicates what?
Sjogren’s syndrome
Speckled anti Scl-70 indicates what?
PSS (systemic)
Speckled anti-centromere indicates what?
PSS (CREST)
Speckled anti-nucleolar indicates what?
SLE and PSS
Of the following diseases:
- SLE
- Drug-induced LE
- Systemic sclerosis (diffuse)
- Limited scleroderma (CREST)
- Sjogren’s,
which has “many nuclear antigens”?
They all do, but SLE and drug induce SLE >95%
Of the following diseases:
- SLE
- Drug-induced LE
- Systemic sclerosis (diffuse)
- Limited scleroderma (CREST)
- Sjogren’s,
which has anti ds-DNA abs?
SLE
Of the following diseases:
- SLE
- Drug-induced LE
- Systemic sclerosis (diffuse)
- Limited scleroderma (CREST)
- Sjogren’s,
which has anti-histones?
> 95% drug induces SLE
Of the following diseases:
- SLE
- Drug-induced LE
- Systemic sclerosis (diffuse)
- Limited scleroderma (CREST)
- Sjogren’s,
which has anti-nuclear RNP?
SLE (30-40%)
Of the following diseases:
- SLE
- Drug-induced LE
- Systemic sclerosis (diffuse)
- Limited scleroderma (CREST)
- Sjogren’s,
which has anti SS-A(Ro) or SS-B(La)?
sjogren
Of the following diseases:
- SLE
- Drug-induced LE
- Systemic sclerosis (diffuse)
- Limited scleroderma (CREST)
- Sjogren’s,
which has anti DNA topoisomerase I (Scl-70)?
Systemic sclerosis (22-36%)
Of the following diseases:
- SLE
- Drug-induced LE
- Systemic sclerosis (diffuse)
- Limited scleroderma (CREST)
- Sjogren’s,
which has anti-smith?
SLE
Of the following diseases:
- SLE
- Drug-induced LE
- Systemic sclerosis (diffuse)
- Limited scleroderma (CREST)
- Sjogren’s,
which has anti-centromeric?
Limited scleroderma (CREST)
Homogenous ANA pattern = ?
RA or drug induced SLE
Rim pattern ANA pattern = ?
SLE active flares
Centromere ANA pattern = ?
CREST syndrome
What are the specific Lupus ANAs?
dsDNA
Anti-Smith
RBCs
Phospholipids
Hyper or hypo coagulability in SLE? Why?
Hypocoag d/t antibodies against Phospholipids
What are the hypersensitivities seen in SLE?
II, III
True or false: any organ can be involved in SLE
True
What causes the arthralgias of SLE?
Immune complexes
What are the histological characteristics of SLE skin rash?
Immune cells beneath the dermis
What are the vascular changes in SLE?
Immune complexes deposit in vascular beds leading to vasculitis
What are the histological characteristics of the vascular changes seen in SLE?
Layered, fibrous thickening (onion staining)
What is the MOA of renal damage in SLE?
Immune complex deposition in the glomeruli
What are the cells that make up the ECM in glomeruli?
Mesangial cells
What is the acute form of serosal membranes in SLE? Chronic?
Acute = exudation of fibrin Chronic = Proliferation of fibrous tissue
What are the heart defects in SLE? (2)
Endocarditis (libman and Sacks)
Pericarditis
Small, warty vegetations along lines of closure of valve leaflets in the heart = ?
Rheumatic heart disease
Large, irregular destructive masses on valve cusps that can extend to the chordae = ?
Infective endocarditis
Small, bland vegetations at the line of closure =?
Nonbacterial thrombotic endocarditis
Small-medium sized vegetations on either/both sides of valve leaflets =?
Libman-Sacks endocarditis
What are the lung changes seen in SLE? Acute, chronic ?
Acute = pneumonitis Chronic = vascular/pulmonary fibrosis
What are the CNS symptoms seen in SLE? MOA?
Focal deficits + Szs
MOA= ?
What are the three major causes of death with SLE?
Renal failure
Infection
CAD
How often does SLE develop in chronic discoied LE?
5-10%
What is subacute cutaneous LE?
Rash, mild systemic disease
How often does SLE develop in chronic discoid LE?
5-10%
What is the treatment for drug induced LE?
Cessation of drug
What are the drugs involved in drug induced Lupus? (4)
D-penicillamine
Procainamide
Hydralazine
Isoniazid
What is Drug induce SLE?
Lupus -like syndrome without Renal or CNS involvement