Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
45 Cards in this Set
- Front
- Back
|
What are the demographic features and epidemiology of SLE?
|
80-90% female
age 15-40 most common among african-american, chinese-american and native american tribes migration to west may increase the risk |
|
|
Factors that modify expression?
|
Environmental
Genetic Hormonal |
|
|
Frequency of SLE?
|
Afro-american>chinese>asian>white
|
|
|
Environmental factors involved in SLE?
|
Sunlight (anti-SSA (Ro)/anti-SSB(La))
Chemicals (Silica, Mercury) Viruses (EBV) Bacteria (Strep) Drugs |
|
|
What drugs influence expression of SLE?
|
Hydralazine
procainamide Dilantin Isoniazid Alpha-methyldopa |
|
|
SLE and Hormones?
|
Female to male ratio, 9:1
Flares are most commonly manifested by females in last trisemester of pregnancy (high Estrogen levels) Associated with BCP use when contains hight esterogen |
|
|
whats the correlation of estrogen with SLE?
|
Overal amount of estrogen is normal
Metabolism of estrogen is causing the lupus: Increased amounts of 16-alpha OH-estrone and decreased 1-oH estron |
|
|
What are the two metabolites of estrogen and whats their effect on epithelial cells and B cells?
|
16-alpha-OH estrone: proliferative and carcinogenic in Epithelial cells, increases anti-dsDNA Ab and igG production in Bcells
2-OH estrone: antiproliferative and protective in Epithelial cells, no effect in B cells |
|
|
How does levels of Androgen changes in SLE?
|
Androgens are immunosuppressive and are decreased in serum of SLE females
|
|
|
What causes excessive immunoreactivity in SLE?
|
increased estrogen metabolism
decreased level of androgens |
|
|
What are the key players in SLE?
|
Environment, Genetics, Hormones lead to immune dysfunction --> autoantibody formation --> immune complex deposition --> features of SLE
|
|
|
How do genetic defects predispose for lupus?
|
lupus associated gene have to contribute to 1 or more essential mechanism that must be implemented to generate SLE susceptibility
these genetic variants prepare immune system and target organs to be responsive to exogenous or endogenous triggers |
|
|
Whats the immune process that leads to lupus?
|
Certain mutations:
activate immune system inappropriately enhance self-antigen presence enhance B and T cell function enhance interaction of phagocytic cell with endothelial cells all these lead to formation of autoantibodies --> target organ death and damage, and expression of lupus |
|
|
Name 4 mechanisms by which lupus associated genes contribute to autoimmunity?
|
1- Some variants facilitate innate immune system activation (by TLRs)
2- Some result in increased availability of self-antigen via defective clearance of senescent cells and/or nuclear material such as DNA 3- Gene mutation may alter the threshold for activation or regulation of the adaptive immune response --> promoting polyclonal activation of B and T cells 4- gene variants promote inflammation and damage target organs by facilitating the interaction of phagocytic cells with the endothelium or failing to protect those organs from pro-inflammatory mediators |
|
|
How does TLR contribute to SLE?
|
Nucleic acids from apoptotic cells can act on certain TLRs and induce production of proinflammatory cytokines : IFN-a and IL-1
|
|
|
What does IFN-a do?
|
macrophage differentiation into DCs
Immunoglobulin class switching primes immune system for increase responsiveness to subsequent stimuli basically it enhances B and T cell function and connect the innate and adaptive immune system. |
|
|
What are the causes of defective clearance of cells in SLE?
|
genetically determined
apoptosis |
|
|
What changes are seen in adaptive immune response in SLE?
|
polyclonal activation of T cells--> induce reactivity against self
polyclonal activation of B cells --> induce autoantibody |
|
|
What is BLyS and what does it do?
|
Cytokine B lymphocyte stimulator is increased in SLE
BLyS promotes B cell survival, differentiation and interaction between co-stimulatory ligands and receptors on B and T cells (CD28-80) These interactions promote B cell differentiation into plasma cells |
|
|
Whats the pattern of ANA in Lupus?
|
Rim like pattern shows DNA Ab produced in the body
|
|
|
What does a homogeneous pattern of ANA indicate?
|
Anit-histone antibody
|
|
|
Speckled pattern in ANA is?
|
anti-Sm
anti-RNP anti-SSA anti-SSB anti-Centromere |
|
|
What are some antibodies found in SLE?
|
Generic ANA = 96%
native dsDNA = 40-60% Smith (Sm) = 20-30% SS-A (Ro) and SS-B (La) = 30-45% |
|
|
Whats Sm?
|
Sm is a specific but not sensitive marker of SLE
|
|
|
Whats ANA?
|
ANA are sensitive but not specific for SLE
|
|
|
What does presence of dsDNA antibody mean?
|
its definitive for the diagnosis of SLE. associated with bothe lupus nephritis and lupus involving the CNS
|
|
|
What type of injury is seen in direct antigen recognition in SLE?
|
immune-mediated hemolytic anemia, thrombocytopenia and leukopenia
|
|
|
Molecular mimicry and SLE?
|
many anti-DNA Ab have cross-reactivity with some renal and brain tissue antigens and may cause damage
|
|
|
where do anti-dsDNA antibodies isolated form SLE patients bind?
|
They bind to glutamate receptors in the hippocampus
|
|
|
What are the immune complexes in lupus?
|
wide rage of autoantibodies may be produced against common cellular constituents such as:
- nucleosome - spliceosome - a small cytoplasmic ribonucleoprotein complex containing Ro (SSA) and La (SSB) Large number of immune complexes are formed and deposited in blood vessels --> potential pleotropic organ involvement in lupus |
|
|
How do immune complexes activate immune system?
|
activation of complemet --> generation of proteins that induce inflammation --> C3a and C5a induce vascular permeability
C3a --> proinflammatory cytokines such as TNF-a, IL-1 and IFN-a and ROS C5a induces migration of phagocytes to area cytokines released in the process of phagocytosis injure bystander cells and tissues membrane attack complex (C5a-C9) promotes lysis and death of surrounding cells |
|
|
What are three types of lupus?
|
Drug induced
neonatal idiopathic (systemic) |
|
|
What are characteristics of Drug-induced lupus?
|
Fever, arthritis, serositis
Rare kidney and CNS involvement ANA is uniformly positive antibody against histone are present (90%) Antibody against Sm and dsDNA are rare disease disappears if stop the drug |
|
|
Whats neonatal lupus?
|
in children born to mothers with antibodies agains SSA and SSB
caused by transplacental passage of IgG autoantibodies cytopenia, hepatosplenomegaly and rash are common Heart block is the most potential consequence disappears postnatally with the half-life of antibody |
|
|
What type of rash is seen in SLE?
|
Butterfly rash
Malar rash Discoid rash Photosensitive skin rash |
|
|
Whats the mechanism of photosensitivity in SLE?
|
UV light at keratinocytes --> autocrine or paracrine release of IL-1 --> SSA translocation to the surface of cell --> anti SSA Ab binds --> immune activation
|
|
|
What are some clinical findings in SLE?
|
Rash
Fever Mucosal ulcers Alopecia Raynaud's phenomenon Arthritis (non-erosive) Renal disorder |
|
|
WHO Classification of Lupus Nephritis?
|
I. normal
II. pure mesangial III. focal segmental IV. diffuse proliferative V. membranous VI. advance sclerosing |
|
|
What are the hematological disorders in SLE?
|
hemolytic anemia
leukopenia thrombocytopenia |
|
|
What are the neurological disorders associated with SLE?
|
Seizures
neuropathies vasculopathy major and minor affective disorder cognitive dysfunction transverse myelitis |
|
|
Cardiac manifestations of SLE?
|
pericarditis
valvular disease Libman-sacks endocarditis accelerated atherosclerosis - MI myocarditis (uncommon) |
|
|
Pleura and Lungs in SLE?
|
pleurisy, pleural effusion (exudate with increased protein and glucose)
Pneumonitis pulmonary hypertension pulmonary embolism pulmonary hemorrhage |
|
|
Whats the clinical manifestation of antiphospholipid syndrome in SLE?
|
vascular thrombosis (both arterial and venous)
recurrent fetal loss decreased platelets |
|
|
what is Antiphosphlipid Syndrome?
|
anitbody to phospholipid beta2-glycoprotein
secondary in SLE APA cross reacts with cardiolipin |
|
|
What does urine analysis of a lupus patient shows?
|
Creatinine may be increased
|
