Autoimmune Diseases and Treatment Strategies
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Questions and Answers

What does plasmapheresis primarily involve?

  • Direct destruction of B cells
  • Periphery nerve stimulation
  • Infusion of synthetic antibodies
  • Exchanging blood plasma for donor plasma (correct)

    • Which cytokine is primarily targeted to reduce pro-inflammatory signaling?

  • IL-12
  • IL-10
  • IL-3
  • IL-6 (correct)

    • What is one of the potential risks associated with plasmapheresis?

  • Infection risk from IV administration
  • Neuropathy from nerve damage
  • Bleeding due to anticoagulants (correct)
  • Increased blood viscosity

    • What is a primary function of intravenous immunoglobulin (IVIG)?

    <p>Acts as antibody replacement therapy (A)</p> Signup and view all the answers

    What condition is IVIG indicated for?

    <p>Immune-mediated thrombocytopenia (A)</p> Signup and view all the answers

    Which mechanism is NOT associated with the action of plasmapheresis?

    <p>Endothelial cell repair (C)</p> Signup and view all the answers

    What are the two types of autoimmune diseases?

    <p>Organ specific and non-organ specific (A)</p> Signup and view all the answers

    What approach is suggested if RA medications stop working?

    <p>Add additional DMARD(s) and modify anti-inflammatory drugs (B)</p> Signup and view all the answers

    What is the primary mechanism of action of methotrexate when used in oncology at high doses?

    <p>Interferes with dihydrofolate reductase (B)</p> Signup and view all the answers

    Which of the following is NOT a recognized solution for managing autoimmune diseases?

    <p>Increase immune system activity (A)</p> Signup and view all the answers

    What does the process of antibody-dependent cellular cytotoxicity involve?

    <p>Macrophages engulfing antigen-antibody complexes (B)</p> Signup and view all the answers

    What is the role of AICAR in the mechanism of action of low-dose methotrexate?

    <p>It increases adenosine levels and signaling (B)</p> Signup and view all the answers

    Which of the following is a type of drug used in the management of autoimmune diseases?

    <p>Cytokine inhibitors (B)</p> Signup and view all the answers

    What is one of the side effects commonly associated with methotrexate?

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

    Which statement best describes the mechanism of action of methotrexate in autoimmune treatments?

    <p>It inhibits cell signaling functions (A)</p> Signup and view all the answers

    Methotrexate is often combined with which drug to prevent Graft-versus-Host Disease (GvHD) in conditions like rheumatoid arthritis?

    <p>Cyclosporine (A)</p> Signup and view all the answers

    Which of the following is NOT a side effect of cyclophosphamide?

    <p>Kidney failure (D)</p> Signup and view all the answers

    What is the mechanism by which methotrexate inhibits cell growth?

    <p>Methotrexate inhibits the production of dihydrofolate reductase, a key enzyme in folate metabolism. (B)</p> Signup and view all the answers

    What is the main goal of precision medicine for treating autoimmune diseases?

    <p>To identify specific molecular pathways driving disease in individual patients or patient groups. (A)</p> Signup and view all the answers

    Which of the following statements is TRUE about rituximab?

    <p>Rituximab is a chimeric monoclonal antibody that targets CD20. (A)</p> Signup and view all the answers

    What is the main goal of inhibitors of cell function, like those used for autoimmune diseases?

    <p>To reduce pro-inflammatory signaling from immune cells. (D)</p> Signup and view all the answers

    Which of the following is NOT a mechanism by which rituximab depletes B cells?

    <p>Direct inhibition of DNA synthesis (C)</p> Signup and view all the answers

    Which of the following statements is TRUE about the dose used in the treatment of autoimmune disease with methotrexate?

    <p>The dose used for autoimmune diseases is lower than that used for cancer patients. (B)</p> Signup and view all the answers

    What is the reason for using B cell-depleting agents in treating autoimmune diseases?

    <p>To target the specific subset of B cells producing autoantibodies. (D)</p> Signup and view all the answers

    Study Notes

    Autoimmune Diseases

    • Two types: organ-specific and non-organ specific
    • Solutions: reducing immune response (immunosuppressants), blocking consequences (anti-inflammatories), replacing/bypassing function (where possible)
    • Management principles: controlling disease, managing flare-ups, limiting drug toxicity

    Drug Groups in Autoimmune Patients

    • Anti-proliferative agents (e.g., cyclophosphamide, methotrexate)
    • Immune cell-depleting agents (e.g., rituximab)
    • Cytokine inhibitors
    • Inhibitors of cell signaling functions
    • Precision medicine

    Cyclophosphamide

    • Inactive form of nitrogen mustard, metabolized to active form in the liver
    • Alkylating agent, binds DNA causing DNA/RNA crosslinking
    • Inhibition of protein synthesis
    • Side effects: alopecia, nausea, bone marrow suppression

    Methotrexate (MTX)

    • Mechanism of action in oncology (high dose): interferes with dihydrofolate reductase (DHFR), reducing DNA synthesis
    • Mechanism of action in autoimmunity (low dose): blocks AICAR transformylase, increases adenosine levels, multiple anti-inflammatory effects via adenosine receptors. Inhibits DHFR, preventing purine and pyrimidine biosynthesis.
    • MTX inhibits DHFR, preventing purine/pyrimidine biosynthesis, blocking DNA/RNA. Accumulates AICAR, broken down into adenosine, inhibiting neutrophil degranulation.
    • Role: inhibits replication of B & T cells; used with cyclosporine to prevent GvHD
    • Side effects: alopecia, bone marrow suppression
    • Autoimmune dose lower than cancer dose
    • Teratogen (causes malformation in embryo)
    • Adenosine receptors: G-protein coupled receptors (A1, A2A, A2B, A3)

    B Cell-depleting agents

    • Used to treat B-cell lymphoma; certain autoimmune conditions (e.g., rituximab)
    • Depletion via ATG or anti-CD25 usually for transplant patients to prevent organ rejection

    Rituximab

    • Chimeric anti-CD20 monoclonal antibody (MAb)
    • Kills normal and malignant B cells expressing CD20
    • Mechanism: ADCC, complement activation, apoptosis.
    • Side effects: reactivation of hepatitis B, progressive multifocal leukoencephalopathy (PML), systemic inflammatory response syndrome (SIRS)
    • Mechanism of action in B cell killing: Complement-mediated cytotoxicity, antibody-dependent cellular cytotoxicity (macrophage), direct lysis (NK cells)

    Plasmapheresis (Plasma Exchange)

    • Removal, treatment, and return of blood plasma
    • Exchanging blood plasma for donor plasma (or other fluids)
    • Used in autoimmune patients
    • Risks: leakage, clotting, bleeding

    Intravenous Immunoglobulin (IVIG)

    • Purified, pooled, sterilized IgG from the plasma of >1,000 donors

    Inhibitors of Cell Function

    • Goal: reduce pro-inflammatory signaling from immune cells

    Precision Medicine in Autoimmunity

    • Goal: to target molecular pathways driving disease in individual patients

    Autoimmune Diseases - General

    • Heterogeneous group of conditions
    • Natalizumab prevents activated T cells migrating into the CNS

    RA (Rheumatoid Arthritis) Treatment Failure

    • Add additional DMARDs and continue anti-inflammatory drugs
    • Potential for synthetic or biologic DMARDs
    • Combination failure may mean different treatment approach

    IVIG Mechanisms

    • Blocks Fc receptors
    • Interferes with complement activation
    • Inhibits T and B cell function
    • Alters immunoglobulin degradation

    RA Immune Mechanisms

    • Multiple mechanisms
    • Anti-rheumatoid factor, anti-CCP antibodies are often found
    • Immune complexes lead to inflammation, increased TNF-alpha production

    RA Management

    • Early diagnosis, specialist care, early initiation of DMARDs
    • Tight control monitoring disease progression
    • NSAIDs and glucocorticoids as adjunctive therapy

    RA Pharmacological Management

    • Start with monotherapy ASAP with oral methotrexate
    • Use anti-inflammatories to accelerate control
    • Once DMARDs effective, reduce and only use glucocorticoids for flare-ups

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    Related Documents

    Immunopharmacology of Autoimmunity PDF

    Description

    This quiz covers key concepts of autoimmune diseases, including their classification into organ-specific and non-organ-specific types. It explores treatment options such as immunosuppressants and anti-inflammatories, as well as specific drug groups like anti-proliferative agents and precision medicine approaches.

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