Autoimmunity

Questions and Answers

What are the two primary processes involved in B-cell production of antibodies?

Clonal expansion and differentiation

Positive selection and apoptosis

Negative selection and proliferation

Negative selection and positive selection (correct)

Which term describes the immune system's ability to tolerate self-tissues?

Autoimmunity

Desensitization

Tolerance (correct)

Immunosuppression

What is a consequence of the breakdown in self-tolerance?

Development of autoimmunity (correct)

Increased immune response to infections

Enhanced tolerance to allergies

Reduction in B-cell activity

What can trigger autoimmunity in susceptible individuals?

Triggering events Signup and view all the answers

What environmental factor can induce autoimmunity, specifically in relation to drug use?

Procainamide Signup and view all the answers

In which gender is Systemic Lupus Erythematosus (SLE) predominantly more prevalent?

Females Signup and view all the answers

What concept explains the immune system's attack on self-antigens that are similar to foreign antigens?

Molecular mimicry Signup and view all the answers

What biological process can contribute to the development of autoimmunity if it is defective?

Apoptosis Signup and view all the answers

Which phase of the cell cycle is characterized by DNA synthesis?

S phase Signup and view all the answers

What is the correct sequence of stages in the cell cycle?

G1, S, G2, M Signup and view all the answers

What occurs during the anaphase of mitosis?

Sister chromatids are pulled apart Signup and view all the answers

What result indicates a negative test in ANA testing during interphase?

No discernible pattern Signup and view all the answers

Which autoimmune disease is associated with a homogeneous pattern in ANA testing?

Systemic Lupus Erythematosus Signup and view all the answers

In ANA testing, how do nucleoli typically behave in interphase cells with a speckled pattern?

Nucleoli usually do not stain Signup and view all the answers

What is indicated by smooth staining of the entire nucleus in interphase cells during ANA testing?

Homogeneous pattern Signup and view all the answers

Which pattern in ANA testing is associated with Systemic Sclerosis and Polymyositis?

Nucleolar pattern Signup and view all the answers

In metaphase cells displaying a homogeneous pattern, where is the staining observed?

Smooth staining of the chromosomal region Signup and view all the answers

What caution should be taken when interpreting the intensity of ANA results?

Do not confuse intensity with positivity Signup and view all the answers

How do interphase cells exhibiting a nucleolar pattern typically manifest in ANA testing?

Staining in the nucleoli only Signup and view all the answers

Which autoimmune diseases are associated with a speckled pattern in ANA testing?

Systemic Lupus Erythematosus and Sjogren's syndrome Signup and view all the answers

What should be avoided to ensure objectivity in ANA interpretation?

Long observation leading to bias Signup and view all the answers

What is a key characteristic of autoimmune diseases classified as organ-specific?

Autoantibodies directed to a specific antigen Signup and view all the answers

Which autoimmune disease is characterized by antibodies against acetylcholine receptors?

Myasthenia Gravis Signup and view all the answers

In autoimmune hemolytic anemia, what do autoantibodies target to initiate hemolysis?

RBC antigens Signup and view all the answers

What primarily distinguishes non-organ-specific autoimmune diseases?

Autoantibodies aimed at a variety of subcellular antigens Signup and view all the answers

Which immunoglobulin class is considered clinically significant regarding Antinuclear Antibodies (ANAs)?

IgG Signup and view all the answers

How many different autoantibodies are estimated to be found in Systemic Lupus Erythematosus (SLE)?

Over 100 Signup and view all the answers

What type of blood sample is required for detecting Antinuclear Antibodies (ANAs)?

Clotted whole blood Signup and view all the answers

What advantage do HEP-2/2000 substrate slides have over rodent substrate slides in detecting autoantibodies?

More sensitivity in detecting specific autoantibodies Signup and view all the answers

What is the function of washing the slides after serum incubation in ANA testing?

To remove unbound antibody Signup and view all the answers

What type of antigen do HEp-2000 cells express that is relevant in ANA testing?

SS-A (Ro) antigen Signup and view all the answers

In ANA testing, what is bound to the substrate during the testing process?

Serum containing ANAs Signup and view all the answers

What happens to ANAs in the serum during ANA testing?

They bind to the cultured cells on the slide Signup and view all the answers

What is the purpose of using a fluorescent microscope after incubation with FITC-labeled secondary IgG?

To visualize the binding patterns of ANAs Signup and view all the answers

What indicates a higher presence of autoantibodies in a serum sample?

Higher titer Signup and view all the answers

Which autoantibodies are specifically associated with systemic lupus erythematosus (SLE)?

Anti-dsDNA Signup and view all the answers

Which of the following conditions is associated with the nucleolar pattern?

Systemic sclerosis Signup and view all the answers

What is the role of dsDNA antigen in the ELISA test for anti-DNA antibodies?

It is the target for antibody binding Signup and view all the answers

What pattern is typically associated with systemic lupus erythematosus (SLE)?

Homogeneous pattern Signup and view all the answers

Which testing method is used for detecting anti-ENA antibodies?

ELISA Signup and view all the answers

What condition is associated with anti-JO-1 antibodies?

Polymyositis Signup and view all the answers

What does the presence of anti-ENA antibodies indicate?

Specific autoimmune condition Signup and view all the answers

What condition is linked to the centromeric pattern?

CREST syndrome Signup and view all the answers

What is a confirmed feature of CREST syndrome?

Sclerodactyly Signup and view all the answers

Which autoantibody is associated with Sjogren's syndrome?

Anti-SSA (RO) Signup and view all the answers

What does a negative ANA pattern typically indicate regarding further testing?

No further tests are necessary Signup and view all the answers

What common testing method is used for both anti-DNA and anti-ENA antibodies?

ELISA Signup and view all the answers

What is the typical arrangement of discrete speckles in metaphase mitotic cells?

Aligned in the chromosomal region Signup and view all the answers

Which autoimmune diseases are commonly associated with the SS-A/RO pattern?

Systemic Lupus Erythematosus and Sjogren's Syndrome Signup and view all the answers

What percentage of samples with anti-SS-A/RO antibodies display the SS-A/RO pattern?

89% Signup and view all the answers

How do hyper-expressing interphase cells differ from non-hyperexpressing interphase cells?

Hyper-expressing cells show stronger nucleolar and speckled staining. Signup and view all the answers

What is the clinical significance of cytoskeletal antibodies?

Linked to autoimmune diseases and Mycoplasma pneumoniae infections Signup and view all the answers

What pattern do mitochondrial antibodies typically display?

Cytoplasmic pattern Signup and view all the answers

How are ribosomal antibodies commonly observed in systemic lupus erythematosus (SLE)?

Seen in approximately 15-20% of cases Signup and view all the answers

What characterizes mixed patterns in autoimmune testing?

They can be any combination of patterns Signup and view all the answers

Why is titering performed on all positive ANAs?

To determine the amount of antibody present Signup and view all the answers

What does titering specifically help determine in ANA testing?

Antibody presence and quantity Signup and view all the answers

Which organelles are recommended for reporting by ANA guidelines?

Golgi apparatus, centriole, and mitotic spindle Signup and view all the answers

What additional feature may be seen in some samples of ribosomal antibodies?

Prominent nucleolar ANA Signup and view all the answers

In what percentage of patients with primary biliary cirrhosis are mitochondrial antibodies detected?

More than 95% Signup and view all the answers

What staining appearance is typical of ribosomal antibodies in the cytoplasm?

Fine speckling Signup and view all the answers

What is a significant preventive measure for SLE patients to ensure heart health?

Regular exercise Signup and view all the answers

What percentage of people with lupus survive 10 years?

85 - 95% Signup and view all the answers

How does older age at onset generally affect the seriousness of SLE?

It generally makes it less serious. Signup and view all the answers

What condition is characterized by dry eyes and dry mouth?

Sjogren's Syndrome Signup and view all the answers

What pattern of ANA is commonly associated with Localised Sclerosis?

Homogeneous Signup and view all the answers

Which autoantibodies are primarily found in Sjogren's Syndrome?

SS-A/RO and SS-B/La Signup and view all the answers

In what ways does Diffuse Systemic Sclerosis typically impact the body?

Affects skin and internal organs Signup and view all the answers

What is the clinical association of Raynaud's Phenomenon?

Sjogren's Syndrome Signup and view all the answers

Which condition is indicated by inflammation of multiple muscles?

Polymyositis Signup and view all the answers

What does CREST stand for in Limited Systemic Sclerosis?

Calcinosis, Raynaud's, Esophageal dysfunction, Sclerodactyly, Telangiectasia Signup and view all the answers

Which subtype of Scleroderma primarily affects areas distal to the elbows and knees?

Limited Systemic Sclerosis Signup and view all the answers

What is a common clinical feature of Diffuse Systemic Sclerosis?

Dermatofibrosis Signup and view all the answers

What distinguishes Limited from Diffuse Systemic Sclerosis?

Limited affects only the skin, diffuse affects organs Signup and view all the answers

What is a characteristic symptom of Dermatomyositis?

Reddish rash Signup and view all the answers

How has the prognosis for Systemic Lupus Erythematosus (SLE) changed over recent decades?

It has improved markedly. Signup and view all the answers

What distinguishes Systemic Rheumatic Diseases from localized conditions?

They affect various organs and tissues throughout the body. Signup and view all the answers

What is the typical female to male ratio in cases of Systemic Lupus Erythematosus (SLE)?

9:1 Signup and view all the answers

Which of the following is a common skin-related symptom of SLE?

Hair loss Signup and view all the answers

What is the typical pattern observed in ANA testing for SLE?

Homogeneous or speckled Signup and view all the answers

What is the primary goal of treatment for SLE?

To control symptoms Signup and view all the answers

Which of the following medications is known to potentially cause Drug-Induced Systemic Lupus Erythematosus?

Chlorpromazine Signup and view all the answers

When do symptoms of drug-induced SLE typically occur after starting the medication?

3-6 months later Signup and view all the answers

What increases the incidence of SLE over the years in the USA?

Better diagnosis and awareness Signup and view all the answers

Which symptom does NOT typically describe SLE?

Increased hair growth Signup and view all the answers

What is the reason for screening for osteoporosis in the treatment of SLE?

To manage side effects of treatments Signup and view all the answers

Which of the following statements about SLE's ethnic prevalence is true?

It varies significantly with ethnicity. Signup and view all the answers

What role does the X-chromosome play in SLE?

It carries genes related to immunity. Signup and view all the answers

Which of the following is a serious complication of SLE?

Lung involvement Signup and view all the answers

What is a common form of managing mild SLE symptoms?

Wearing protective clothing and using NSAIDs Signup and view all the answers

Study Notes

B-cell Antibody Production and Autoimmunity

Two main processes for B-cell production of antibodies: positive selection and negative selection.
Tolerance refers to the immune system's ability to tolerate self-tissues, preventing autoimmunity.
Breakdown in self-tolerance results in autoimmunity, often marked by autoantibody production.
Genetic predisposition significantly contributes to the etiology of autoimmune diseases.
HLA-B27 is notably associated with Ankylosing Spondylitis, increasing risk by 90 times.

Triggers and Factors of Autoimmunity

Autoimmunity can be triggered by various events.
Environmental factors, such as drug-induced reactions (e.g., procainamide), can provoke autoimmunity.
Systemic Lupus Erythematosus (SLE) shows a higher prevalence in females.
Defective apoptosis may lead to loss of tolerance, contributing to autoimmune conditions.

Autoimmune Disease Classification

Organ-specific autoimmune diseases involve autoantibodies targeting specific antigens (e.g., Myasthenia Gravis - AChR autoantibodies).
Non-organ-specific autoimmune diseases generate autoantibodies against various organelles or subcellular components (e.g., SLE and Rheumatoid Arthritis).
Autoantibodies can recognize a diverse range of cellular structures leading to systemic effects.

Antinuclear Antibodies (ANAs)

ANAs bind specifically to the nucleus and can belong to IgG, IgM, or IgA classes.
IgG is deemed clinically significant among ANA classes.
The incidence of ANAs increases with age and can indicate systemic rheumatologic conditions.
ANA tests are useful for diagnosing patients exhibiting relevant symptoms.

ANA Testing Procedures

Blood samples for ANA testing require clotted whole blood collected in red-topped vacutainers.
Serum is separated post-centrifugation and tested against substrates coated with cultured cells (e.g., HEp-2, HEp-2000).
Positive ANA tests display fluorescent patterns under a microscope, which can vary based on antibody type.

ANA Patterns and Clinical Significance

Homogeneous patterns are associated with SLE and feature smooth nuclear staining in interphase cells.
Speckled patterns, indicative of various autoimmune diseases (e.g., SLE, Sjogren's syndrome), show coarse or fine staining in the nucleus.
Nucleolar patterns are associated with Systemic Sclerosis, demonstrating staining exclusive to nucleoli.
Centromere patterns, often seen in CREST syndrome, show discrete speckling within the nucleus.

Cytoplasmic Antibodies in Autoimmunity

Cytoskeletal, mitochondrial, and ribosomal proteins are notable cytoplasmic antigens in autoimmune diseases.
Mitochondrial antibodies are present in over 95% of primary biliary cirrhosis cases.
Ribosomal antibodies appear in approximately 15-20% of systemic lupus erythematosus cases, associated with neuropsychiatric symptoms.

Mixed Patterns in Autoimmune Testing

Mixed patterns can show combinations of staining and require careful interpretation and reporting of all observed patterns and titers.
Titering is performed on positive ANAs to quantify the antibody levels and support diagnosis.
Follow-up tests, including anti-DNA and ENA testing, may be recommended based on pattern analysis.

Conclusion on ANA Testing

Understanding the classification of ANA patterns is crucial for diagnosing autoimmune diseases.
Insights into both organ-specific and non-specific autoimmune conditions provide a framework for targeted patient management.
Proper interpretive methods and technology in ANA testing enhance diagnostic accuracy and therapeutic approaches in autoimmunity.### Autoantibodies and Testing
Follow-on tests for positive ANAs are crucial to clarify unclear staining patterns and confirm conditions like systemic lupus erythematosus (SLE).
Negative ANA patterns require no further testing.
Anti-DNA antibodies are tested using ELISA, which involves immobilizing double-stranded DNA on a plate to detect IgG antibodies in patient serum.
Anti-ENA antibodies are also tested via ELISA, with extractable nuclear antigens (such as RO, LA, Sm, RNP/Sm, Scl 70, and JO-1) immobilized on the plate.
Homogeneous and speckled ANA patterns are prominently associated with SLE.

Systemic Lupus Erythematosus (SLE)

SLE presents with diverse symptoms affecting skin, joints, lungs, and kidneys; it's chronic, with remissions and relapses.
A notable female-to-male ratio of 9:1; commonly appears in the second or third decade of life.
Incidence in the USA increased significantly from 1.0 per 100,000 in 1955 to current rates of 53 to 305 per 100,000, influenced by improved diagnostics.
Prevalence varies by ethnicity, with higher rates in Afro-Caribbean individuals (159/100,000).

Symptoms and Diagnosis

Common symptoms include joint pain (arthralgia), skin rashes (butterfly rash), fever, anemia, renal issues, and Raynaud's phenomenon.
Diagnosis involves clinical presentation, ANA testing, antibody titration, and possibly follow-up DNA/ENA tests.
Specific auto-antibodies like anti-dsDNA and anti-Sm are strongly correlated with SLE.

Treatment Approaches

Treatment focuses on symptom management; aggressive therapy is necessary for severe cases involving organs like kidneys and heart.
Options include NSAIDs, corticosteroids, antimalarials (hydroxychloroquine), and cytotoxic drugs.
Monitoring for osteoporosis is crucial due to prolonged corticosteroid use.

Prognosis

Prognosis has improved; early treatment positively influences long-term outcomes, with approximately 85-95% survival over ten years.
Later-onset SLE is generally less severe than early-onset forms.

Other Systemic Rheumatic Diseases

Systemic rheumatic diseases are characterized by non-organ-specific symptoms.
Examples include Sjogren's Syndrome, Scleroderma, and Polymyositis.
Sjogren's is characterized by dry eyes and mouth; autoantibodies include SS-A and SS-B.
Scleroderma divides into localized and systemic types, with varying clinical implications, generally involving skin and potentially major organ systems.

Scleroderma Details

Limited Scleroderma often presents as CREST syndrome, exhibiting calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia.
The centromeric pattern of ANA is prevalent in limited systemic sclerosis.
Diffuse Scleroderma affects multiple organ systems and has a higher ANA positivity rate (70-90%).

Polymyositis and Dermatomyositis

Polymyositis affects multiple muscles; Dermatomyositis additionally causes skin inflammation (characterized by a reddish rash).
Common symptoms include muscle weakness and soreness, with potential involvement of the heart and GI tract.
The JO-1 antibody is frequently found in these conditions.

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Description

Test your knowledge on B-cell production and the immune response. This quiz covers key concepts such as positive and negative selection, self-tolerance, and the consequences of autoimmunity. Challenge yourself and see how well you understand these vital immunological processes.