Autoimmunity (Exam 2) Flashcards
The ability of the immune system to accept self-antigens and not initiate a response against them.
self-tolerance
What can a loss of self-tolerance result in?
autoimmunity
Tolerance that occurs in primary or central lymphoid organs and is also called negative selection of self-reactive lymphocytes.
central tolerance
Lymphocytes that recognize self-antigens in secondary lymphoid organs are rendered incapable of reacting with those organs. This type of immunological tolerance is where self-reactive lymphocytes are terminated to avoid an autoimmune disorder.
peripheral tolerance
The fact that many bacterial or viral agents have antigens that closely resemble the structure or amino acid sequence of self-antigens.
molecular mimicry
How can the MHC molecular structure affect or cause autoimmunity?
If a self-antigen is able to bind to the peptide cleft of the molecule, it will be presented by the MHC to killer T cells, therefore causing autoimmunity.
Is autoimmunity more prevalent among people of the same family or among unrelated people?
People of the same family
Is autoimmunity more prevalent among identical twins (monozygotic) or non-identical (dizygotic) twins/siblings?
Identical twins
What gene is heavily focused on in the genetic research of autoimmunity?
The MHC gene
Is SLE an example of a systemic or organ specific autoimmune disease?
systemic
Is RA an example of a systemic or organ specific autoimmune disease?
systemic
Is Goodpasture’s syndrome an example of a systemic or organ specific autoimmune disease?
organ specific
Is myasthenia gravis an example of a systemic or organ specific autoimmune disease?
organ specific
Is scleroderma an example of a systemic or organ specific autoimmune disease?
organ specific
Is Sjogren’s syndrome an example of a systemic or organ specific autoimmune disease?
organ specific
Fatigue, weight loss, malaise, fever and anorexia are among the first to appear.
Effects of nonspecific involvement (of SLE)
The most frequently reported manifestation (over 90% of patients); Polyarthralgia and typically symmetric arthritis in small joints of the hands, wrists, and knees.
Effects of joint involvement (of SLE)
The second most frequently occurring manifestation (approx. 80% of patients); Skin manifestations including an erythematous rash in areas contacted by UV and the classic butterfly rash on the face.
Effects of uncommon appearance (of SLE)
The most common cause of death in patients with SLE
The deposition of immune complexes in kidney tissue leading to renal failure
Patients with this disorder may experience any of the following systemic effects: renal failure, cardiac issues (tachycardia, pericarditis, or ventricular enlargement), pleuritis, neuropsychiatric manifestations, and hematologic abnormalities.
The patient has SLE
A specific state of unresponsiveness to antigens is known as…
Anergy
What percentage of the population is affected by autoimmunity?
5-7%
When does central tolerance take place?
When B cells mature in the bone marrow.
When does peripheral tolerance take place?
After T and B cells mature and enter periphery
The following defects are all caused by what?
Abnormal expression, dysfunction of signaling molecules, dysregulation of cytokines, Fc receptor polymorphisms.
B-cell defects
Defects of polyclonal B-cell activation may be enhanced by…
Gran-negative bacteria and many viruses (ex. CMV and EBV)
Fluorescent anti-nuclear antibody
FANA
Extractable nuclear antigen
ENA
If an FANA result is positive, what is the next step to be completed?
Profile testing
Pattern with a smooth, even staining or the nucleus with or without apparent masking of the nucleoli.
Homogenous patten
Pattern with fluorescence most intensely concentrated at the periphery of the nucleus with a large ring starting from the internal nuclear membrane.
Peripheral pattern
Pattern with large speckled covering the whole nucleoplasm.
Speckled pattern
Pattern with 23 or 46 bright speckles or void granules spread over the nucleus of interphase cells.
Nucleolar
What two autoimmune disorders are ENAs associated with?
Mixed Connective Disease and SLE
What is peak onset age for SLE?
20-40 yo
Is SLE more common in men or women?
Women
What HLA isotypes are associated with SLE?
HLA-DR and HLA-DQ
Which types of assay has the higher specificity for antigens, ENA or FANA?
ENA
What happens to B and T cells in a patient with SLE?
B cells increase and T cells decrease
A homogenous pattern in SLE diagnosis shows evidence of which autoantibodies?
Anti-DNA, Anti-DNP, and Anti-histone
A peripheral pattern in SLE diagnosis shows evidence of which type of autoantibodies?
Anti-DNA
A speckled pattern in SLE diagnosis shows evidence of which type of autoantibodies?
Anti-RNP, Anti-SSA/SSB
What is the typical onset age for RA?
between 35-50 yo
How many times more likely are women to get RA than men?
3 times
What genes and alleles are specifically associated with RA?
MHCII genes and DR4 alleles
What are the three most common forms of treatment for SLE?
Antimalarials or topical steroids, High dose of aspirin or anti-inflammatory, Systemic corticosteroids
Which immunoassay detects presence of autoantibodies in the blood by using six extractable nuclear proteins?
Extractable nuclear antigen (ENA) assay
Which immunoassay detects the presence of ANAs in patient serum by adding the serum to a microscopic slide fixed with animal or human cells, doing a wash step, and then adding fluorescent tagged anti-human Ag?
Fluorescent antinuclear antibody (FANA)
Malaise, fever, weight loss, and transient joint pain
Effects of non-specific involvement (of RA)
Symmetrical affects to the joints; stiffness and pain in joints that is worse in the morning and gets better throughout the day; joint pain starting in smaller joints and spreading into larger joints such as knees, hips, cervical spine, and shoulders; osteoporosis in 20-30% of patients; joint pain that leads to muscles spasms and limited range of motion
Effects of join-involvement (of RA)
IgM antibody against the Fc portion of the IgG molecule
Rheumatoid factor (RF)
What is the most common cause of death in patients with RA?
Cardiovascular disease
Formation of subcutaneous nodules, pericarditis, lymphadenopathy, splenomegaly, interstitial lung disease, or vasculitis; development of nodules over bones; development of Sjogren’s syndrome or Fetyl’s syndrome; cardiovascular disease
Systemic effects of RA
How does RF play a role in pathogenesis of RA?
It increases macrophage activity and enhances antigen presentation to T cells by APCs
Antibody to cyclic citrullinated proteins
Anti-CCP
The lead marker for detection of RA, more specific than the other
Anti-CCP
How do labs test for RF?
Latex agglutination test; agglutination occurs if RF is present
How do labs test for anti-CCP?
ELISA
What are the three main forms of treatment for RA?
Non-steroidal anti-inflammatory drugs (NSAIDs), Anti-rheumatic drugs, and joint replacement
What ANA pattern is often observed for patients with RA?
Speckled pattern; typically directed against ribonucleoprotein
What is a limitation of screening tests for RF and anti-CCP?
They can yield false negatives and false positives
What are the common autoantobodies for Sjogren’s syndrome?
anti-SS-B and anti-SS-B
Are patients with Sjogen’s RF positive?
Yes
Is Sjogen’s more common in women or men
90% more common in women
What disorder is described by the following symptoms?
Inflammation of the salivary and lacrimal glands leading to dryness of the eyes and mouth, joint pain, vaginal dryness leading to yeast infections, persistent dry cough, and prolonged fatigue
Sjogren’s syndrome
What are the common autoantibodies of Scleroderma?
Anti-Scl-70
What are the common autoantibodies of scleroderma?
Anti-Scl-70
What disorder is described by the following symptoms?
Thickening and tightening of skin caused by excessive deposits of collagen, petechiae, reddish/scaly skin, and visible blood vessels.
Scleroderma
What is the ANA pattern for scleroderma?
Speckled pattern and centromere pattern
Are patients with scleroderma RF positive?
Yes
What disorder are the specific symptoms describing?
Calcinosis Raynaud phenomenon Esophageal dysfunction Sclerodactyly Telangiectasia
CREST syndrome, a limited form of scleroderma
What disorder is described by the following symptoms?
Weakening of the skeletal muscle due to damage to the acetylcholine receptors, facial weakness, drooping of eyelids, and difficulty swallowing.
Myasthenia Gravis
What autoantibodies are associated with Myasthenia Gravis?
Anti-AChR (binding, blocking, disrupting)
Anti-MuSK (muscle kinase)
Anti-LRP4 (lipoprotein)
What autoantibodies are associated with Goodpasture’s syndrome?
Autoantibody to the glomerular, renal tubular and alveolar basement membranes (renal and pulmonary basement membranes)
What disorder is described by the following symptoms?
Foamy, bloody or dark colored urine, decreased urine output, cough with bloody sputum, difficulty breathing after exertion, weakness, fatigue, nausea/vomiting, weight loss, nonspecific chest pain, and pale skin
Goodpasture’s syndrome