Gen Path Exam 3 - Autoimmune Disease - Lupus Flashcards
Caused by immune rxn against self
Autoimmune disease
What 3 things classify autoimmune diseases?
Autoimmune rxn
Rxn is not secondary to tissue damage
Absence of another cause of disease
Autoimmune diseases affect what % of US population?
1-2%
What is the spectrum of autoimmune diseases?
Organ-specific to generalized/systemic
Conditions in which immune response is directed against a single organ or tissue
Organ-specific
Autoimmune rxn is against widespread antigens
Generalized/systemic
What are the 2 forms of lupus?
Systemic
Cutaneous
Cutaneous lupus is divided into what 3 subtypes?
Acute
Subacute
Chronic
Common form of chronic cutaneous lupus
Discoid lupus
Occurs in absence of systemic disease, or may occur in association with Systemic Lupus
Discoid lupus
Risk of progression to Systemic Lupus is 16.7% within 3 years of diagnosis
Discoid lupus
Many features in common with Systemic Lupus and characteristically develops in people w/o history of systemic autoimmune diseases
Drug-induced lupus
What are the 2 drugs with the highest risk of Drug-induced lupus?
Procainamide
Hydralazine
Prototypical multisystem autoimmune disease characterized by production of numerous autoantibodies, especially antinuclear anitbodies (ANAs)
Systemic lupus
15-17% of Systemic lupus cases occur prior to the age of ____, with peak incidence being in the age range of ______ years
16; 20-40
Systemic lupus occurs ____ times more frequently in females age 17 to 55 years
9
Has a 2-3x higher prevalence among blacks and hispanics than in whites
Systemic lupus
What disease?
Autoantibodies are directed against nucleoproteins, erythrocytes, leukocytes, platelets, coagulation factors, and organs such as the liver, kidneys, heart
Systemic lupus
T/F: Systemic lupus has a variety of clinical manifestations
True
What disease?
Specific etiology is not known with certainty, but immunocomplexes, autoantibodies, and genetic, infectious, environmental, and endocrine factors play significant roles
Systemic lupus
What is the fundamental systemic pathogen mechanism in Systemic lupus?
Failure to maintain immunological self-tolerance
In systemic lupus, what does failure to maintain immunological self-tolerance lead to?
Production of lots of autoantibodies -> damages tissues secondary to immune complex deposition
In systemic lupus, failure to maintain immunological self-tolerance, production of autoantibodies, and damage to tissues secondary to immune complex deposition are consistent with what type of rxn?
Type III hypersensitivity rxn
In systemic lupus, autoantibodies specific for RBCs, WBCs, and platelets opsonize these cells and promote their _____________, resulting in _________
phagocytosis; cytopenias
In systemic lupus, autoantibodies specific for RBCs, WBCs, and platelets are consistent with what type of rxn?
Type II hypersensitivity rxn
In systemic lupus, the formation of what is thought to be related to the decreased functioning of suppressor T-cells and hyper-autoreactive B-cells?
Autoantibodies
What accounts for majority of tissue damage seen in systemic lupus?
Immunocomplexes
What do the immunocomplexes that account for majority of tissue damage in systemic lupus mostly consist of?
Nucleic acid + IgG
What do the immunocomplexes that account for majority of tissue damage in systemic lupus activate and attract?
Activate complement
Attract neutrophils + macrophages
In systemic lupus, what 3 things are the result of immunocomplexes activating complement and attracting neutrophils + macrophages?
Vasculitis
Fibrosis
Tissue necrosis
In systemic lupus, pts with increased circulating immunocomplexes have more severe damage, particularly affecting which organ?
Kidney
In systemic lupus, immunocomplexes also account for tissue damage in which 3 organs in the body (besides kidney)?
CNS
Skin
Lungs
T/F: There is familial association with Systemic lupus, meaning family members have an increased risk of developing it
True
What disease?
High rate of concordance in monozygotic twins vs dizygotic twins
Systemic lupus
What disease?
Relative risk for persons with HLA-DR2 or HLA-DR3 is 2 to 3, and if both haplotypes are present, the risk is about 5
Systemic lupus
What disease?
Genetic deficiencies of complement proteins, (especially C1q, C2, or C4) are seen in ~ 10% of patients
Systemic lupus
In systemic lupus, genetic deficiencies of complement proteins may result in defective clearance of immune complexes and ________ cells, and failure of ____ cell tolerance
apoptotic; B
What exacerbates the lesions of systemic lupus?
UV radiation
In systemic lupus, UV radiation causes _________ of host cells, leading to an
increased burden of nuclear fragments and
inflammatory responses to the products of dead cells
apoptosis
What has been associated with the development of systemic lupus since it modulates the production of autoantibodies?
Cig smoking
What disease?
10x more common in women during reproductive years than in men of similar ages, but only 2-3x more common in women during childhood or after the age of 65
Systemic lupus
What disease?
Tx of women with oral contraceptives w/ high doses of estrogen and progesterone did NOT influence the frequency or severity of disease flares, suggesting that factors other than hormones may account for increased risk of this disease in women
Systemic lupus
Virus-like particles of ______ viruses have been detected in tissues of pts w/ Systemic lupus
RNA
What specific viruses have been reported to occur with increased frequency in pts with Systemic lupus?
Epstein-Barr (EBV)
Cytomegalovirus (CMV)
Varicella-Zoster (VZV)
What 3 components of the immune system play a role in the pathogenesis of Systemic lupus?
Type 1 interferons
Toll-like receptors
Failure of B cell tolerance
Which component of immune system in Systemic lupus?
Blood cells show molecular signature that indicates exposure to IFN-α; may also produce abnormally large amounts of IFN-α
Type 1 interferons
Which component of immune system in Systemic lupus?
Recognize DNA and RNA, notably the DNA-
recognizing TLR9 and the RNA-recognizing TLR7
Toll-like receptors
Which component of immune system in Systemic lupus?
Produce signals that activate B cells specific for self nuclear antigens
Toll-like receptors
Which component of immune system in Systemic lupus?
Defects in both central & peripheral B cell tolerance result in a higher frequency of autoreactive B cells
Failure of B cell tolerance
What disease?
Disease with multi-organ involvement
Systemic lupus
In systemic lupus, immunocomplex deposition causes ____________, which leads to renal, cardiovascular, mucocutaneous, and CNS destruction
small-vessel vasculitis (aka lupus vasculitis)
In systemic lupus, inflammation of ________ ___________ results in joint, peritoneal, and pleuropericardial symptoms
serous membranes
What disease?
As there is no typical pattern of presentation; one patient may present with dermatitis and kidney disease whereas another may present with arthritis, anemia, and pleurisy
Systemic lupus
When a patient demonstrates signs/symptoms of multi-organ involvement, what disease should be considered in the differential diagnosis, especially for a female who is 20 to 40 years of age?
Systemic lupus
What are many of the pathologic changes seen in Systemic lupus due to?
Lupus vasculitis
Why does lupus vasculitis occur in Systemic lupus?
Autoimmune-mediated inflammatory changes
In Systemic lupus, where do autoimmune-mediated inflammatory changes most commonly occur?
Small blood vessels