Rheumatoid Arthritis Overview and Risk Factors
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What percentage of pregnant women with RA experience spontaneous remission?

  • 90%
  • 50%
  • 75% (correct)
  • 85%

What is a common outcome for women with RA shortly after delivery?

  • Continued remission
  • Improved overall health
  • Flare of symptoms (correct)
  • Disease resolution

What is the likelihood of spontaneous remission occurring in pregnant women with RA?

  • 75% (correct)
  • 50%
  • 40%
  • 25%

In what period do symptoms of RA typically increase for pregnant women after childbirth?

<p>Within weeks after delivery (A)</p> Signup and view all the answers

What does RA stand for in the context of pregnancy health?

<p>Rheumatoid Arthritis (C)</p> Signup and view all the answers

Which cytokine is primarily responsible for the induction of Th1 cells?

<p>IL-12 (B)</p> Signup and view all the answers

What characteristic effector cytokine do Th1 cells secrete?

<p>IFN-gamma (B)</p> Signup and view all the answers

Th2 cells are primarily induced by which cytokine?

<p>IL-4 (B)</p> Signup and view all the answers

Which of the following cytokines is NOT secreted by Th2 cells?

<p>IL-12 (D)</p> Signup and view all the answers

What is a characteristic feature of Th1 cells compared to Th2 cells?

<p>Induced by IL-12 (C)</p> Signup and view all the answers

Which aspect of the immune system is influenced by Interleukin 6?

<p>Hematopoiesis and multiple cell types (A)</p> Signup and view all the answers

What type of biological activity does Interleukin 6 primarily exhibit?

<p>Pleiotropic effects influencing systemic inflammation (B)</p> Signup and view all the answers

Which of the following statements about Interleukin 6 is accurate?

<p>It promotes systemic inflammation through hematopoiesis. (B)</p> Signup and view all the answers

In terms of immune system modulation, Interleukin 6 is known to affect which of the following?

<p>Hematopoiesis and various immune cell types (C)</p> Signup and view all the answers

How does Interleukin 6 contribute to systemic inflammation?

<p>By influencing hematopoiesis and immune cell activities (A)</p> Signup and view all the answers

What is the primary role of Interleukin 18 in the immune response?

<p>It induces the production of various proinflammatory cytokines. (D)</p> Signup and view all the answers

Which of the following cytokines is NOT induced by Interleukin 18?

<p>IL-10 (A)</p> Signup and view all the answers

Which cell type is primarily involved in the production of cytokines induced by Interleukin 18?

<p>Synovial macrophages (C)</p> Signup and view all the answers

What family of cytokines does Interleukin 18 belong to?

<p>IL-1 family (C)</p> Signup and view all the answers

Which of the following cytokines is known to enhance inflammatory responses, acting as an important factor in immune activation along with Interleukin 18?

<p>IL-1beta (C)</p> Signup and view all the answers

What is the primary cause of the early reversible loss of proteoglycans?

<p>Catabolic effect of cytokines (C)</p> Signup and view all the answers

Which enzymes are involved in the degradation process that affects proteoglycans?

<p>Stromelysins and aggrecanases (B)</p> Signup and view all the answers

What type of loss occurs before the permanent damage to proteoglycans?

<p>Reversible loss (B)</p> Signup and view all the answers

What is one of the key cytokines elevated by interleukin 1 that contributes to inflammation?

<p>IL-6 (D)</p> Signup and view all the answers

What role do cytokines play in the loss of proteoglycans?

<p>Have a catabolic effect (D)</p> Signup and view all the answers

Which of the following substances is NOT synthesized due to the influence of interleukin 1?

<p>Monocyte colony-stimulating factor (A)</p> Signup and view all the answers

What role does collagenase play in the context of inflammation as influenced by interleukin 1?

<p>Breaking down cartilage (C)</p> Signup and view all the answers

What could be a likely consequence of the production of stromelysins and aggrecanases?

<p>Degradation of proteoglycans (A)</p> Signup and view all the answers

Which of the following is NOT a product synthesized as a response to interleukin 1?

<p>Interferon gamma (C)</p> Signup and view all the answers

Which inflammatory mediator is associated with interleukin 1 in promoting inflammation?

<p>Granulocyte macrophage colony-stimulating factor (B)</p> Signup and view all the answers

Flashcards

Pregnancy and RA remission

A significant portion (75%) of pregnant women with rheumatoid arthritis (RA) experience a temporary remission of the disease.

Postpartum RA flare

After giving birth, the RA in most women tends to return or worsen.

Rheumatoid Arthritis (RA)

An autoimmune disease that causes chronic inflammation of the joints.

Spontaneous remission

The disease subsides without any specific treatment.

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Percentage of remission

75% of pregnant women with RA experience a temporary remission period.

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Th1 cell subtype

A type of T helper cell activated by IL-12, secreting IFN-gamma and IL-2.

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Th2 cell subtype

A type of T helper cell activated by IL-4, secreting IL-4 and IL-10.

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Cytokines

Signaling proteins that mediate immune responses.

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IL-12

A cytokine that activates Th1 cells.

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Effector cytokines

Cytokines that carry out the action of a specific cell type.

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Interleukin-1 (IL-1)

A cytokine that stimulates inflammation.

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Inflammation in RA

Inflammation is a key feature of rheumatoid arthritis (RA).

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Increased IL-6 synthesis

IL-1 triggers the production of more IL-6, a pro-inflammatory cytokine.

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Chemokines and GM-CSF

IL-1 also increases the production of chemokines, attracting immune cells, and GM-CSF, stimulating immune cell activity.

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Prostaglandins and Collagenase

IL-1 elevates the production of prostaglandins (pro-inflammatory) and collagenase (breaks down tissue).

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Interleukin 18 (IL-18)

A pro-inflammatory cytokine of the IL-1 family

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Pro-inflammatory cytokine

A type of protein that triggers inflammation

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Synovial macrophages

Immune cells in the joints, affected by IL-18

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IFN-γ, IL-8, GM-CSF, TNF-α

Cytokines produced by synovial macrophages in response to IL-18

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IL-1 family

A group of proteins that includes Interleukin-18

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Interleukin-6 (IL-6)

A cytokine that has widespread effects on inflammation and the immune system.

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Pleiotropic effects

Having multiple and diverse effects.

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Systemic inflammation

Inflammation throughout the entire body.

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Hematopoiesis

The process of blood cell production.

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Immune system cell types

Cells that participate in the immune response.

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Proteoglycan loss

A reversal in the presence of proteoglycans happens early, likely from cytokines and enzymes.

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Cytokine catabolic effect

Cytokines cause proteoglycan breakdown, impacting joint health.

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Stromelysins and Aggrecanases

Enzymes that break down proteoglycans, contributing to joint damage.

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Early proteoglycan loss

Loss of joint proteoglycans occurs initially during the disease process.

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Joint tissue breakdown

The degradation of joint proteoglycans contributes to joint damage.

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Study Notes

Rheumatoid Arthritis: Epidemiology, Pathology, and Pathogenesis

  • Rheumatoid arthritis (RA) is a common inflammatory arthritis causing pain, disability, and mortality.
  • RA primarily affects small joints in hands and feet, but larger joints can be involved too.
  • Extra-articular manifestations and systemic symptoms can also occur.
  • RA is a heterogeneous disease with variable severity and unpredictable response to therapy.
  • Genetic and environmental factors play a role in etiology and pathogenesis.

Role of HLA-DR and Shared Epitope

  • The most significant genetic risk factor for RA is certain HLA (human leukocyte antigen) alleles, particularly DR alleles.
  • Specific amino acid sequences (the shared epitope) are prevalent in RA patients.
  • Various models explain the role of the shared epitope in RA, including efficient binding to arthritogenic peptides, and T-cell selection/regulation.

Nongenetic Risk Factors: Influence of Sex

  • Women are more likely to develop RA than men (2-3 times).
  • Estrogen may play a role in this gender difference, potentially affecting B-cell apoptosis and T cell subsets.

Environmental Factors and RA Risk

  • Smoking significantly increases the risk of developing RA, especially in those with the shared epitope.
  • Exposure to various environmental factors and infectious agents may contribute to the development of RA.

Pathology of Rheumatoid Arthritis

  • Chronic inflammation in the synovium (lining of the joint) is central.
  • Proliferating synovial cells form pannus, which invades and destroys cartilage and bone.
  • Cytokines (e.g., TNF-α, IL-1, IL-6) are key drivers of inflammation and bone erosion.
  • Immune complexes and complement activation contribute to inflammation and joint damage.
  • Extra-articular manifestations involve various organs and systems.

Pathological Findings in Synovial Tissue

  • Increased numbers of various inflammatory cells (including T cells and B cells) and synoviocytes (synovial lining cells).
  • Synovial hypertrophy and villous projections extending into the joint.
  • The lining layer might thicken, sometimes up to 10 cell layers thick.

Cartilage and Bone Destruction

  • Aggressive synoviocytes, chondrocytes, and PMNs (polymorphonuclear leukocytes) are involved in cartilage destruction.
  • Enzymes like MMPs (matrix metalloproteinases) breakdown cartilage and extracellular matrix.
  • Focal bone erosions occur, possibly due to osteoclast activation.
  • Periarticular bone loss and generalized osteopenia can increase fracture risk.

Cytokine Networks: Macrophages and Fibroblasts

  • Synovial macrophages and fibroblasts are primary cytokine sources in RA.
  • These cells release various proinflammatory cytokines like IL-1, IL-6, TNF-α, and chemokines.
  • These cytokines directly or indirectly contribute to inflammation, cartilage and bone degradation, and blood vessel formation.

Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibodies

  • Anti-CCP antibodies are highly specific and sensitive for diagnosing RA.
  • The presence of both Anti-CCP and rheumatoid factor increases the likelihood of more severe RA disease.

Role of T Cells in RA

  • Naive CD4+ T cells differentiate into multiple effector types (Th1, Th2) depending on the environment.
  • Th1 cells contribute to the defense against intracellular pathogens, and Th2 cells are involved in allergic reactions and responses to extracellular parasites.
  • Both types can also contribute to autoimmune diseases, including RA.

Role of B cells in RA

  • B cells produce rheumatoid factors (RF) and anti-citrullinated peptide antibodies (anti-CCP)
  • The production of these antibodies can contribute to RA tissue damage.

Diagnosis of RA

  • Blood tests (RF, anti-CCP antibodies) and imaging (X-rays) are used for diagnosis.
  • Other symptoms and physical examination are also part of the evaluation.

Treatment of RA

  • Disease-modifying anti-rheumatic drugs (DMARDs) are used to manage disease activity.
  • Biologics are targeted therapies that provide additional treatment options.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammation.
  • Corticosteroids can be used in severe cases.

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Description

This quiz explores the epidemiology, pathology, and pathogenesis of rheumatoid arthritis (RA), a prevalent inflammatory joint disease. It delves into genetic risk factors like HLA-DR and the shared epitope, as well as the influence of sex on the development of RA. Test your knowledge on the complexities and dynamics of this condition.

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