Autoimmune
Clinical Laboratory Science Mmbio 423 with Zundel at Brigham Young University
About this deck
By: Lyndee Francom
Textbook:
Clinical Laboratory Chemistry
Created: 2011-10-17
Size: 128 flashcards
Views: 8
Textbook:
Clinical Laboratory ChemistryCreated: 2011-10-17
Size: 128 flashcards
Views: 8
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What is an autoimmune response?
The immune system reacts against the individual's own cells.
What are ways the body is able to recognize its own cells (self) vs. non self cells?
Clonal Deletion, MHC antigen presentation, Antigen sequestering, Interactions of all immune cells, effector cells and cytokines
What is autoimmunity?
The breakdown of the the mechanisms to distinguish between self and foreign antigen
Name 4 contributing factors to autoimmunity
1) Molecular mimicry 2) Environmental conditions 3) Genetic Predisposition 4) Hormone influences
What is molecular mimicry?
viral and bacterial antigens are so similar to self antigens that an immune response to the pathogen results in an attack on self antigens (cross reacting) some pathogens are able to change antigens to appear like self cells
What is cross reactivity? (in autoimmunity)
Molecular mimicry
What disease is abbreviated SLE?
Systemic Lupus Erythematosus aka Lupus
What is Lupus (SLE)?
A CHRONIC SYSTEMIC inflammatory disease that involves multiple body systems.
What type of immune response is seen with lupus?
Complement fixing complexes such as antibodies with DNA are deposited in the kidney, skin, joints and choroid plexus.
What is one of the frequent targets of antibodies/complement fixing complexes in lupus?
Nuclear particles (DNA, etc)
What areas of the body are frequently affected by lupus?
Kidney, skin, joints, and choroid plexus.
What is the choroid plexus?
Structure in the ventricles of the brain where cerebrospinal fluid (CSF) is produced.
What is the cause of SLE (lupus)?
It is unknown. Possibilities are genetic, hormonal, environmental and drug induced.
What are the most common symptoms of lupus (SLE)?
Joint pain (arthritis), sensitivity to infections, swollen lymph glands, acute and chronic glomerulonephritis, increased premature birth and spontaneous abortion (miscarriage), Cardiac problems such as pericarditis, tachycardia, ventricular enlargement, & photosensitive rash.
Is the course of the disease predictable?
No, it is highly variable.
What does "highly variable" refer to in SLE?
It is completely different from individual to individual and also an individual may have periods of remission and periods of disease.
What tissues are most commonly affected in SLE?
Connective tissues
What are the functions of the glomerulus and nephrons?
filtering and concentrating
What does "Lupus" mean?
Wolf-like
What is a photosensitive rash?
A rash that develops on skin exposed to UV light
What do we call the signature rash for lupus that covers the bridge of the nose and cheeks?
A "butterfly rash"
What percent of patients with lupus exhibit a photosensitive rash?
30-40%
What would you be likely to see in a CBC (complete blood count) of a Lupus patient with regards to RBC's WBC's, and platelets?
RBC's - increased hemolysis, elevated WBC , decreased platelets
Are CRP's increased or decreased in SLE (lupus)?
increased
A urinalysis in a person with lupus would likely show which of the following? a) blood b) decreased proteins c) bacteria d) increased proteins
a and c - blood and increased proteins
If you performed a BUN on a lupus patient would creatinine levels be increased or decreased?
increased due to renal damage
What is acrocyanosis and what laboratory findings go along with this condition?
bluish or cyanotic color of the extremities (most often hands)/Cryoglobulins
What would the complement profile in lupus look like?
C3 and C4 would be decreased
What test is ANA and what would the results in lupus be?
Anti-nuclear antibody - this is frequently seen in lupus
What tests on a lupus patient often get a false positive?
STS or RPR (tests for syphilis), and RA/RF (rheumatoid arthritis/rheumatoid factor)
What are STS and RPR tests?
Serum test for syphilis and rapid plasma reagin (also for syphilis)
What are RA and RF?
Rheumatoid arthritis and rheumatoid factor
What is an IFA?
Indirect fluorescent antibody
Explain how IFA is done in 7 steps. (8?)
1) Mouse kidney or human epithelial cells are fixed to a slide 2) a patient's serum is added and incubated and allowed to react with the cells on the slide 3)Incubate* 4) Fluorescent (Fluorescein isothiocyanate) labeled anti-human globulins (AHG anti-antibodies) are added 5)labeled AHG reacts with Antibodies attached to the antigen (cells on slide) 6) Slide is washed to removed excess AHG 7) the fluorescence is observed (titer or pattern) *In lecture bill stated that there would be another wash after the incubation of the serum and slide - this would make 8 steps
What are the two methods used to read an IFA?
Titer (serial dilution) and pattern
Explain what the following results of IFA indicate. (in SLE) a) less than or equal to 20 b) 1:40 to 1:160 c) greater than 160
a) negative b) suggestive of presences of ANA's (anti nuclear antibodies) c) highly suggestive of ANA's
What does a homogenouse or diffuse IFA pattern look like?
The entire nuclease is glowing GREEN.
What Antibodies are present in a diffuse or homogenous pattern?
Anti DNA -histone (anti-nucleoprotein) anti DNP (deoxyribonucleoprotein)
What disease(s) is/are associated with a diffuse or homogeneous IFA pattern?
SLE (lupus) or RA (rheumatoid arthritis)
1. What does a negative pattern look like?
No fluorescence in the cell. It might be greenish, but it isn't glowing
2. What does a peripheral or rim pattern look like?
The fluorescence is just along the edge-where the antibodies are attaching
3. What antibodies are present in a peripheral or rim pattern?
Anti-DNA, Anti-dsDNA, Anti-nDNA
4. What disease is associated with a peripheral/rim pattern?
SLE (Lupus)
5. What does a light speckled pattern look like?
Only a few speckles in each cell
6. What does a heavy speckled pattern look like?
Very dense fluorescence all throughout the cell
7. What other pattern can heavy speckled be confused with?
homogenous
8.When is heavy speckled pattern the most helpful?
When we know only an anti-Sm is present, which is specific for Lupus
9.What does a nucleolar pattern look like?
Just the nucleoli of the cells are fluorescent
10. What antibody is present in a nucleolar pattern?
Anti-nucleolar RNA
11. What diseases are associated with a nucleolar pattern?
Scleroderma and Sjogren's Syndrome
12.What is the purpose of ANA?
screening test
13. What is the next step if you get a positive ANA?
Get more specific-react patients serum with extractable antigens
14. What extractable antigen is associated with SLE(lupus)?
Anti-DNA
15. What 2 types of DNA can you test for in Lupus
DS-DNA and SS-DNA
16. What type of assay do you use to test for SS-DNA?
RIA
17. What percentage of patients with Lupus have Anti-Sm?
0.3
18. What antibody is associated with MCTD (mixed connective tissue disease)?
Anti-RNP
19. What is the treatment for Lupus patients?
corticosteroids/prednisone
20. What do corticosteroids do?
Reduce the immune process
21. What is another type of immunodiffusion test we can do for ANA?
Ouchterlony
22. What type of inflammatory disorder is Sjogren's Syndrome?
Chronic systemic
23. In Sjogren's Syndrome, what part of the body do antibodies target?
mucus secreting glands-salivary, tear ducts, etc.
24. Is Sjogren's Syndrome a life threatening condition?
No-but very annoying
25. What is the major symptom of Sjogren's Syndrome?
no saliva, no tears (ex:eat a cracker without saliva)
26. What gender and age group does Sjogren's Syndrome primarily affect?
women and elderly patients
27. Why does Sjogren's Syndrome primarily affect women?
Estrogen enhances immune responses
28. What is the characteristic symptom of Scleroderma?
hardening of the skin-tissue turns fibrotic
29. What disease state can Scleroderma progress to?
systemic sclerosis
30. What substance gets deposited into the internal organs?
Collagen
31. What organ is primarily affected?
esophagus-you can't swallow or eat
32. How severe is Scleroderma?
very-5 year survival rate is about 40%
33. What are common symptoms with Scleroderma?
Can't relax mouth or purse lips together, can't move hands(collagen deposits in joints), poor cirulation
What does the ANA pattern look like for polymyositis?
Speckled
Which antibody is present for polymyositis?
Anti-ribonucleoprotein (ant-RNP)
What are the symptoms of the inflammatory myopathy of polymyositis?
Muscle weakness, inflammation, gradual onset, trouble speaking, swallowing, fatigue.
What ages is polymyositis seen at?
30-50 years old
What causes polymyositis?
It is unknown, possibley bacterial or viral trigger.
What can be seen with dermatomyositis?
Rash
What does the ANA pattern look like for MCTD?
High titer/ heavy speckling is indicative of MCTD.
Which antibody is present for MCTD?
Anti-ribonucleoprotein (ant-RNP)
What does MCTD stand for?
Mixed connective Tissue Disease
Why can it be hard to distinguish between Lupus, scleroderma and polymositis?
They have overlapping symptoms.
Why do you want to moniter MCTD closely?
It can progress to full blown SLE
How is Rheumatoid Arthritis similar to SLE?
Systemic, occurs between ages 20-40, and more frequently in women.
What is RA caused by?
Unkown cause, possibly viral.
Do women or men die earlier than expected?
women
What is the mortality rate for RA
Men die 4 years earlier, and women die 10 years earlier.
What is the Rheumatoid factor?
IgM antibody
How does IgM work as the Rhuematoid factor?
It activates compliment, and is directed against the Fc portion of IgG, which complexes together and gets stuck in the joints.
Why is IgM more important than IgG
Only one IgM is needed to activate compliment and 2 IgG's are needed.
Is IgM specific for RA?
no
What is the association of Rheumatoid factor and RA?
Is it associated with increased morbidity and amplifies inflammation.
What happens in result of the IgM complexes?
The joints lose their cushion, and just bone on bone is left.
What happens when polyclonal activation of B cells occur?
It results in production of HUGE amounts of anti IgG antibodies.
What are some other antibodies associated with RA
ANA, anticollagen
What could happen as a result of the collection of antibodies?
The immune complex formation and activation of complement. (And that makes for a bad day)
What causes joint injuries?
Invasion of macrophages and neutrophils
What could happen to the cell that line the synovium?
They start to proliferate.
What are some symptoms of RA?
malaise, fever, weight loss, joint pain. (these are nonspecific)
What is unique about the progression of RA
It starts in small joints and moves to larger ones and often in a symmetric fashion.
How does joint pain lead to muscle spasms?
The muscle is trying to overcompensate for the joint deformity.
How frequent are nodules present in RA?
25% of cases
What are the nodules like?
Necrotic areas surrounded by mononuclear cells with an outer zone of granulation tissue containing plasma cells and lymphocytes.
What are the 6 criteria for RA?
Morning stiffness, arthristis of 3 or more joints, arthritis of hand joints, symmetric arthritis, serum RF, radiographic changes.
How many of the criteria are needed to diagnose RA?
3 or 4 (not all will be present)
What does the RA laboratory profile look like?
Increases CBC, ESR and CRP
What does the CBC look like?
Increased platelets, WBC, Lymph's, Decreased RBC, Hct and anemic.
What is the compliment profile of RA?
Decreased C3 an C4.
What does the ANA look like?
20% positive
What can be seen in the synovial fluid?
crystals
What does the protein pattern look like?
Acute or chronic inflammatory pattern on electrophoresis.
What is another name for the RA test?
RF Test (They are interchangeable)
Descibe the Latex agglutination test.
latex beads are coated with IgG and patients serum is added. (IgG and IgA will be present but IgM is what we are looking for. Agglutination will occur in the presence of the IgM antibody.
(Questions 42-47were not mentioned in class but are on the slides) What is the sensitivity of the latex test?
75-80%
What is the Specificity of the latex test?
0.75
What can result in a false positive from the latex test?
SLE, Syphilis, Liver disease, Sjogren's syndrome, 3% of normal population
What can result in a false negative from the latex test?
IgG-RF, and IgA-RF
what is the Sensitivity of the Rose-Waaler hemagglutination test?
60-70%
what is the Specificity of the Rose-Waaler hemagglutination test?
0.9
Do we perform the Rose-Waaler hemagglutination test?
No.
What quantitative tests can be done?
ELISA for IgM, and nephelometry
What is a new diagnostic test for RA?
Anticyclic citrullinated Peptide (anti-CCP)
How does the anti-CCP test work?
Autoantibodies are directed against the peptide containing unusual amino acid citruline.
Is anti CCP specific for RA?
Yes, it is not usually present but is in RA.
What is the frequency of anti-CCP?
60-80%
How is RA treated?
The treatment is only palliative (treats symptoms) Asprin and NSAID's are used.
What are newer treatments and how do they work?
Monoclonal antibody against specific cells and treatment with cytokine inhibitors. They reduce the inflammatory process.
What are DMARD's and how do they work?
Diseases modifying anti-rheumatic drugs. They block TNF - Tissue necrosing factor.
About this deck
By: Lyndee Francom
Textbook: Clinical Laboratory Chemistry
Created: 2011-10-17
Size: 128 flashcards
Views: 8
Textbook:
Clinical Laboratory ChemistryCreated: 2011-10-17
Size: 128 flashcards
Views: 8
About StudyBlue
STUDYBLUE makes things that make you better at school.
Things like online flashcards with photos and audio.
Things like personalized quizzes and friendly reminders about when (and what) to study next.
Think of it as a digital backpack™: access to all of your study materials online and on your phone.
STUDYBLUE exists to make studying efficient and effective for every student, for free. Join us.
“Simply amazing. The flash cards are smooth, there are many different types of studying tools, and there is a great search engine. I praise you on the awesomeness.”
Dennis
Dennis