Immunopharmacology
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Questions and Answers

What is primarily required for Cell Mediated Immunity to function effectively?

  • B cells
  • Antibodies
  • Viable T-cell lymphocytes (correct)
  • Natural killer cells

Which type of T-cell is responsible for activating cytolytic T lymphocytes in response to an antigen?

  • CD8 T-cells
  • CD4 T-cells (correct)
  • B cells
  • NK cells

What type of immunity involves the production of antibodies to bind to antigens in solution?

  • Cell mediated immunity
  • Humoral immunity (correct)
  • Innate immunity
  • Passive immunity

In the Plaque Antibody Forming Cell (PFC) Assay, what is the role of the sheep red blood cells (RBC)?

<p>To stimulate an immune response in the mouse (C)</p> Signup and view all the answers

What is one characteristic of acquired immunity?

<p>It is enhanced by repeated exposure. (D)</p> Signup and view all the answers

What does the ELISA assay utilize to detect antibodies?

<p>Fluorescent tags or enzymes (D)</p> Signup and view all the answers

Which of the following is not a component of the antibody production system in acquired immunity?

<p>Natural killer cells (D)</p> Signup and view all the answers

What is the primary functionality of the innate immune system?

<p>Phagocytosis of bacteria (B)</p> Signup and view all the answers

Which of the following cells is NOT a component of the innate immune system?

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

What role do complement proteins play in innate immunity?

<p>Creating pores in bacterial cell membranes (C)</p> Signup and view all the answers

How does the innate immune system differ from the acquired immune system?

<p>The innate immune system provides nonspecific defense. (C)</p> Signup and view all the answers

Which process involves recognition and ingestion of bacteria by cells of the innate immune system?

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

What type of immune response is characterized by its rapid activation and lack of immunological memory?

<p>Nonspecific immune response (B)</p> Signup and view all the answers

In the context of innate immunity, which of the following accurately describes macrophages?

<p>They are released from bone marrow as mature cells. (C)</p> Signup and view all the answers

Which of the following drugs is known to inhibit angiogenesis and is highly regulated due to potential birth defects?

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

What is the primary mechanism of action for Mycophenolate Mofetil?

<p>Inhibition of purine synthesis (D)</p> Signup and view all the answers

Which drug is a prodrug of mercaptopurine that blocks purine nucleic acid synthesis?

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

Which type of monoclonal antibody consists of approximately 66% human content?

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

What kind of drug mechanism do Leflunomide and Teriflunomide share?

<p>Inhibition of pyrimidine synthesis (A)</p> Signup and view all the answers

Which immunosuppressive drug is specifically designed to block the signaling mechanism of mTOR?

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

Which of the following drugs acts as an alkylating agent to destroy proliferating lymphoid cells?

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

What is the primary purpose of antibody hybridoma cells in monoclonal antibody production?

<p>To isolate and grow antibody producing cells (A)</p> Signup and view all the answers

Which type of hypersensitivity reaction is characterized by an immediate response mediated by IgE antibodies?

<p>Type I Antibody Mediated (D)</p> Signup and view all the answers

What is the major consequence of the Type II antibody-mediated hypersensitivity reaction?

<p>Destruction of red blood cells (B)</p> Signup and view all the answers

In which type of hypersensitivity reaction do macrophages play a significant role and the response occurs 2-3 days after exposure?

<p>Type IV Cell Mediated (A)</p> Signup and view all the answers

Autoimmunity occurs when the antibody response is directed against which of the following?

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

Which disease is NOT generally classified under immunodeficiency diseases?

<p>Rheumatoid arthritis (D)</p> Signup and view all the answers

What primary function does cyclosporine serve in organ transplantation?

<p>Blocks T-cell activation (B)</p> Signup and view all the answers

Which of the following accurately describes an effect of drugs like cortisone?

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

Which enzyime is inhibited by the action of calcineurin inhibitors like cyclosporine?

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

What is the primary use of Rho (D) immune globulin in pregnant women?

<p>To prevent Rh hemolytic anemia of the newborn. (C)</p> Signup and view all the answers

What is the mechanism of action of RhoGAM® in preventing hemolytic disease of the newborn?

<p>It blocks the recognition of Rh positive red cells by maternal immune cells. (D)</p> Signup and view all the answers

How long does the protection from immune globulins typically last?

<p>1-3 months (B)</p> Signup and view all the answers

In which situation is Rho (D) immune globulin primarily administered postpartum?

<p>To clear potential Rh positive fetal red cells from maternal circulation. (B)</p> Signup and view all the answers

What is the source of the immune globulin preparations used in immunotherapy?

<p>Polyclonal human immunoglobulin obtained from healthy human donors. (C)</p> Signup and view all the answers

What condition is associated with the need for specific immune globulin preparations besides Rho (D)?

<p>Respiratory syncytial virus infection (D)</p> Signup and view all the answers

What type of immune response is characterized by antibodies (IgG) being demonstrated in plasma with symptoms like autoimmune hemolytic anemia?

<p>Type II (D)</p> Signup and view all the answers

What would be the consequence if an Rh negative mother generates antibodies against Rh positive red blood cells during her first pregnancy?

<p>Future Rh positive pregnancies may put the baby at risk of hemolytic disease. (B)</p> Signup and view all the answers

Which of the following symptoms is NOT typically associated with serum sickness?

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

What type of patients would most benefit from receiving immune globulin therapy?

<p>Patients at high risk for contracting a disease and needing immediate protection. (A)</p> Signup and view all the answers

Which agents are released by mast cells that contribute to airway smooth muscle contraction in asthma?

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

What is the primary role of Omalizumab in immunotherapy?

<p>Blocking IgE binding to mast cells (C)</p> Signup and view all the answers

Which cytokines are released due to antigen binding to mast cells and lead to eosinophil activation?

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

In Type II hypersensitivity, which type of antibodies bind to the antigen during a transfusion reaction?

<p>IgM or IgG antibodies (C)</p> Signup and view all the answers

What is the mechanism by which plasmapheresis alleviates symptoms of serum sickness?

<p>Removing the drug from circulation (B)</p> Signup and view all the answers

Which of the following is primarily responsible for the edema and mucus hypersecretion observed in allergic reactions?

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

What is used to measure acquired immunity?

<p>Plaque Antibody Forming Cell (PFC) Assay (A)</p> Signup and view all the answers

What is used to measure innate immunity?

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

What do most glucocorticoids inhibit?

<p>B cell proliferation (A)</p> Signup and view all the answers

What is the mechanism of action (MOA) of methotrexate?

<p>Inhibition of dihydrofolate reductase (A)</p> Signup and view all the answers

Why is methotrexate used to treat rheumatoid arthritis?

<p>It inhibits the metabolism of folic acid, reducing inflammation. (A)</p> Signup and view all the answers

How does the dosing of methotrexate differ between its use in cancer chemotherapy versus rheumatoid arthritis (RA) treatment?

<p>Methotrexate is given in higher doses for cancer chemotherapy than for RA. (A)</p> Signup and view all the answers

What are some adverse drug reactions (ADRs) associated with the use of oral corticosteroids?

<p>All of the above (D)</p> Signup and view all the answers

What is the mechanism of action (MOA) of nonsteroidal anti-inflammatory drugs (NSAIDs)?

<p>Inhibition of cyclooxygenase (COX) enzymes (A)</p> Signup and view all the answers

What are a few NSAID drugs that are mostly over the counter (OTC) drugs? (Select all that apply)

<p>Ibuprofen (A), Aspirin (B), Naproxen (C)</p> Signup and view all the answers

Match each drug to its appropriate class

<p>Glucocorticoids = cortisol derivatives Proliferation Signal Inhibitors = sirolimus Calcineurin Inhibitors = cyclosporin, tacrolimus Other Agents = mycophenolate, thalidomide, azathioprine, cyclophosphamide</p> Signup and view all the answers

Which of the following drugs is described by the following characteristics:

  • Drugs interfere with the cell cycle of lymphoid cells
  • Drugs reduce antibody levels (especially IgG)
  • Contact hypersensitivity abrogated (abolished) by drugs?

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

Which of the following drugs is described by the following characteristics?

  • Used to suppress the immune system in organ transplants
  • Peptide antibiotic in structure
  • Blocks activation of T cells
  • Binds to cyclophilin protein, inhibiting the cytoplasmic phosphatase enzyme, calcineurin
  • Administered intravenously and orally, but poorly absorbed when taken orally.

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

Which of the following is described as: -a macrolide antibiotic that is similar in actions to cyclosporine -binds to immunophilin FK-binding protein, inhibits calcineurin -blocks T cell activation

  • is 10-100 times more potent than cyclosporine
  • is used both orally and intravenously as well as in a topical preparation for atopic dermatitis and psoriasis?

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

Which of the following is used as an alternative to cyclosporine when it does not work?

<p>Mycophenolate Mofetil (B)</p> Signup and view all the answers

Which of the following conditions is Azathioprine used for?

<p>Rheumatoid Arthritis (RA) (A), Lupus Erythematous (LE) (B), Multiple Sclerosis (MS) (C)</p> Signup and view all the answers

Which of the following is used in host vs graft disease?

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

Which of the following is only used to treat rheumatoid arthritis?

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

Which of the following is described:

  • antimalarial with immunosuppressant properties
  • drug decreases T-cell activation
  • used for lupus erythematosus (LE) and rheumatoid arthritis (RA)?

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

Match each item to its description

<p>Bevacizumab = vascular endothelial growth factor inhibitor Cetuximab = epidermal growth factor inhibitor Rituximab = CD20 malignant B lymphocytes inhibitor Arcitumomab = antibody to CEA fragment labeled with technetium 99m</p> Signup and view all the answers

Which of the following are anti-TNF alpha monoclonal antibodies (MABs)?

<p>Adalimumab (A), Etanercept (B), Infliximab (C)</p> Signup and view all the answers

Match each item to its description

<p>Adalimumab = (a) used for RA; (b) dose sc every other week, half life 2 weeks Etanercept = (a) dimeric fusion protein (a target protein fuse; (d) in RA dose every other week sc onto an IgG;(b) made of human IgG constant region fused to TNF receptor; c) drug blocks TNF mediate inflammation by binding TNF produced by the patient; Infliximab = (a) chimeric antibody used in RA and other autoimmune disorders Abatacept = (a) recombinant fusion protein;(b) binds to CD80 or CD86 and blocks T cell activation and release of cytokines;(c) used in RA when other drugs have failed</p> Signup and view all the answers

Match each item to its description

<p>Alefacept = (a) used to treat plaque psoriasis;(b) binds to CD2 receptors and block cell activation Omalizumab = (a) anti-IgE antibody;(b) blocks binding of IgE to mast cells and basophils;(c) used in treatment of asthma alemtuzumab = binds to CD52 receptors on normal and malignant B and T lymphocytes; treats B-cell chronic lymphocytic leukemia ofatumumab = binds to CD20 receptors on all B cells which leads to cell destruction</p> Signup and view all the answers

Match each item to its description

<p>panitumumab = binds to EGFR rituximab = chimeric binds to CD20 on normal and malignant B lymphocytes trastuzumab = binds to the HER-2/neu receptor on epidermal growth factor; drugs block binding of growth factor to breast tumors abciximab = binds to GPIIb/IIIa receptors on platelets and prevents aggregation</p> Signup and view all the answers

Which of the following binds to and inhibits the maturation of osteoclasts in bone?

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

CHOP + rituximab for some forms of non-Hodgkin's lymphoma has shown cure rates of over 85%

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

Flashcards

Innate Immunity

The body's first line of defense against infections, non-specific and lacks immunological memory.

Phagocytosis

The process where immune cells engulf and destroy pathogens like bacteria.

Macrophages

Immune cells that are precursors to monocytes and crucial for phagocytosis.

Complement Proteins

Proteins that enhance the immune response by marking pathogens for destruction.

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Phagocytosis Assays

Laboratory tests to measure the phagocytic activity of macrophages.

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Innate Immunity Summary

Summary of the innate immune system, including key roles, cells, mediators, and lack of specificity and memory.

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NK cells

Natural Killer cells, part of the innate immune system, which destroy virus-infected and cancerous cells.

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Opsonization

The process of coating a pathogen to make it more recognizable and digestible for phagocytes.

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Cell-mediated Immunity

An immune response where T-cells directly attack and destroy infected cells, without the use of antibodies.

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Humoral Immunity

An immune response that uses antibodies to target pathogens in body fluids.

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Antigen-Presenting Cell (APC)

A cell that displays an antigen to a T-cell to trigger an immune response.

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Lymphocytes

White blood cells that are key players in the adaptive immune response, including T cells and B cells.

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Acquired Immunity

The body's ability to recognize and destroy specific pathogens after a previous encounter.

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Antibody Production

The process where B-cells produce antibodies that specifically bind to and neutralize foreign materials.

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Cytokines

Chemical messengers that regulate the immune response, activating and signaling other cells.

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Plaque Assay

A lab test to measure antibody production by cells, visualising how many antibody-producing cells there are.

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Hypersensitivity Reactions

An exaggerated immune response to a normally harmless substance, leading to tissue damage.

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Type I Hypersensitivity

Immediate allergic reaction caused by IgE antibodies binding to mast cells and basophils, releasing histamine.

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Type II Hypersensitivity

Antibody-mediated destruction of cells due to the formation of antigen-antibody complexes that activate complement.

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Type III Hypersensitivity

Immune complexes deposit on tissues, triggering inflammation and tissue damage.

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Type IV Hypersensitivity

Delayed hypersensitivity reaction mediated by T-cells, occurring 2-3 days after exposure.

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Autoimmunity

Immune response where the body attacks its own tissues, recognizing them as foreign.

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Immunodeficiency Diseases

Conditions where the immune system is weakened, making individuals more susceptible to infections.

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Immunosuppressive Drugs

Medications that suppress the immune system, often used to prevent organ rejection after transplant.

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Tacrolimus MOA

Tacrolimus is a macrolide antibiotic that blocks calcineurin, an enzyme responsible for T-cell activation. This inhibits the production of IL-2, a crucial cytokine for T-cell proliferation.

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Sirolimus MOA

Sirolimus blocks the mTOR signaling pathway, which is critical for cell growth and proliferation. This inhibits the activation and proliferation of T cells, suppressing the immune response.

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Mycophenolate Mofetil MOA

Mycophenolate Mofetil inhibits the production of purines, essential building blocks for DNA and RNA. This disrupts the function of T and B cells, preventing them from multiplying and mounting an immune response.

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Thalidomide MOA

Thalidomide inhibits angiogenesis, reduces inflammation, and blocks TNF-alpha production, a key cytokine involved in inflammation. It also reduces phagocytosis by neutrophils.

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Azathioprine MOA

Azathioprine is a prodrug that gets converted to mercaptopurine, which inhibits the production of purines. This disrupts DNA and RNA synthesis, blocking cell proliferation.

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Cyclophosphamide MOA

Cyclophosphamide is an alkylating agent that damages DNA, preventing cell division. This directly kills proliferating lymphoid cells involved in the immune response.

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Leflunomide and Teriflunomide MOA

Leflunomide and Teriflunomide inhibit the synthesis of pyrimidines, another essential building block for DNA and RNA. This disrupts lymphocyte activation and proliferation.

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Monoclonal Antibody Production

Monoclonal antibodies are produced by fusing a mouse antibody-producing B-cell with a human myeloma (bone marrow cancer) cell, creating a hybridoma cell. Hybridoma cells produce large amounts of identical antibodies that target a specific antigen.

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Immune Globulin

A concentrated preparation of antibodies from pooled human donors, providing temporary passive immunity to specific diseases.

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Passive Immunity

Immunity acquired by receiving antibodies from another source, such as through immune globulin injections, rather than generating them yourself.

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Polyclonal Antibodies

Antibodies generated from multiple B-cells that recognize different epitopes on a target antigen.

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When are Immune Globulins Used?

Immune globulins are used in situations where there is a need for immediate protection against a specific disease, or in patients with low immune function.

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Rho(D) Immune Globulin

A specific type of immune globulin that prevents Rh hemolytic disease of the newborn by blocking Rh-positive red blood cells from triggering an immune response in the mother.

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Hemolytic Disease of the Newborn

A condition where the mother's antibodies attack the baby's red blood cells, leading to anemia and other complications.

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Rh Incompatibility

A condition where the mother is Rh-negative and the baby is Rh-positive, which can trigger the mother to produce antibodies against the baby's blood.

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How Does Rho(D) Immune Globulin Work?

It binds to Rh-positive red cells in the mother's blood, preventing the mother's immune system from targeting them and triggering antibody production.

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Drug Allergy (Type II)

A drug triggers an autoimmune response, like the immune system attacking its own tissues. An example is systemic lupus erythematosus caused by procainamide.

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Drug Allergy (Type III - Serum Sickness)

This reaction involves the immune system reacting to a drug and causing symptoms like rashes, fever, joint pain, and swollen lymph nodes.

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Mast Cells in Asthma

These cells are present in the lungs. When triggered by allergens, they release substances like histamine, which cause bronchoconstriction and airway inflammation.

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Immuno Model of Asthma

In this model, an allergen enters the airways and binds to IgE antibodies on mast cells. This triggers the release of inflammatory mediators, leading to asthma symptoms.

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Eosinophils in Asthma

These white blood cells are also activated during an asthma attack. They release substances that worsen inflammation and contribute to airway narrowing.

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Anti-IgE Antibodies (Omalizumab)

These are monoclonal antibodies that bind to IgE, preventing its attachment to mast cells and reducing the release of inflammatory mediators.

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Omalizumab Mechanism

This drug, a humanized monoclonal antibody, works by attaching to IgE, preventing it from binding to mast cells. This stops histamine release when the body encounters the allergen.

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Omalizumab Effects

This drug effectively lowers the levels of IgE in the blood to below detectable levels. It is given through an injection.

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Study Notes

Pharmacology I - Immunopharmacology

  • Immunopharmacology is a chapter 55 topic in PM 716
  • Lecture covers the immune system (innate and acquired), antibodies as drugs, abnormal immune responses, autoimmunity, immunodeficiency replacement, immunosuppression agents, cytotoxic agents, and immunomodulating agents.
  • Immune System: innate (primitive) and acquired (adaptive).
    • Adaptive immunity includes cell-mediated immunity (CMI) and humoral immunity. CMI involves T-cells and minimal antibody role. Viable T-lymphocytes are necessary, while humoral involves antibody production in solution and activation of the complement cascade
  • Innate Immunity:
    • First line of defense against bacterial and viral infections.
    • Nonspecific and has no memory.
    • Involves NK cells and macrophages.
    • Complement proteins bind to bacterial surfaces, creating pores and initiating apoptotic cell death (opsonization).
    • Phagocytes kill bacteria through free radical destruction and lysozyme digestion.
    • Cells involved are granulocytes, monocytes, and NK cells.
  • Macrophages:
    • Develop from monocytes released from bone marrow.
    • Account for 1-10% of total white blood cells (WBC).
    • Phagocytize bacteria.
  • Measurement of Innate Immunity:
    • Phagocytosis Assays: macrophages are coated to a titer well plate, then radioactive red blood cells are added to evaluate phagocytosis.
  • Immunosuppressive Drugs:
    • Cortisone: gold standard for immunosuppression
    • Calcineurin Inhibitors: Cyclosporine, Tacrolimus
    • Proliferation Signal Inhibitors: Sirolimus, Everolimus
    • Mycophenolate Mofetil: inhibits T and B cell response via purine synthesis.
    • Thalidomide: used in various diseases, inhibits angiogenesis, anti-inflammatory, reduces neutrophil phagocytosis, but highly regulated due to birth defects.
    • Cytotoxic Agents: Azathioprine, Cyclophosphamide, and more.
  • Antibodies as Drugs:
    • Monoclonals: mice are injected with an antigen to isolate antibody-producing B lymphocytes from the mouse spleen; these B cells are fused with human B lymphocytes (from myeloma) to grow hybridoma cells; antibodies are harvested for treatment. Monoclonal antibodies can be mouse, chimeric (~66% human), or humanized (~90+% human) to reduce immunogenicity.
  • Antibody Drug Examples:
    • Abciximab (ReoPro), Rituximab (Rituxan), Trastuzumab (Herceptin). Various other examples are given involving TNF-alpha blockage or the use of human constant IgG attached to TNF-alpha receptor for treatment.
  • Monoclonal Antibodies: Trastuzumab is a recombinant DNA-derived humanized monoclonal antibody.
    • Blocks overexpression of the HER-2/neu receptor associated with some breast cancers, thereby inhibiting protein synthesis crucial to tumor growth.
    • Infliximab binds TNF-alpha (a cytokine for inflammatory response), showing improvement in RA patients.
  • Immune Globulins:
    • Passive immunization obtained through injections of specific, pooled immune globulins.
    • Used in cases where disease is present, in patients with decreased immune response, or those at high risk of contracting the disease, but no time for vaccine.
    • Protection lasts 1-3 months, primarily using purified IgG fractions from pooled human donors. -Specific Immune Globulins: preparations are available for a wide range of conditions including CMV, Hep B, Rabies, Tetanus, and Respiratory Syncytial Virus.
    • Immune globulin (IgG) iv (Gamimune)
      • Polyclonal human immunoglobulin. Obtained from thousands of healthy donors.
      • Drug at 2g/kg modulates the patient immune response, lowers T-cell numbers. Used for various immune disorders.
  • Rh(D) Immune Globulin: Used to prevent Rh hemolytic anemia in newborns.
    • A pregnancy with an Rh-negative mother and Rh-positive baby runs the risk of mother forming antibodies against Rh-positive fetal cells, causing issues in subsequent pregnancies. Administered within 24-72 hours after delivery.
  • Hypersensitivity Reactions: -Type I: immediate, IgE mediated; basophils (plasma), and mast cells; rapid release of histamine in response to antigen. Examples include hives, asthma, etc.
    • Type II: foreign antigen + IgM or IgG antibody leads to complex binding to red blood cells, complement activation, and red cell destruction. Examples include incompatible blood transfusions, penicillin allergies, and Rh incompatibility.
    • Type III: antigen-antibody complexes precipitate onto basement membranes, causing tissue damage (e.g., kidneys) due to complement release.
    • Type IV: delay of 2-3 days, cell-mediated response (e.g., macrophages, cytokines) with delayed release of digestive enzymes and tissue damage. Examples include contact hypersensitivity, poison ivy reactions. -Immunological reactions to drugs: drugs may cause allergic reactions.
    • Type I: IgE-mediated acute response
    • Type II: drug forms an neoantigen with patient proteins
    • Type III: serum sickness; drug causing antigen-antibody complexes
    • Type IV: cell-mediated allergic response. -Autoimmunity: T and B lymphocytes fail at recognizing self and non-self; examples include RA, systematic lupus erythematosus, multiple sclerosis, and type 1 diabetes; related to various disease states and conditions.
  • Immunodeficiency Diseases: Decreased immune function leading to infections, often genetic, and the example of HIV.
  • Tuberculin Skin Test for TB: tuberculin is a glycerin extract of tubercle bacilli and other components; the PPD is a protein derivative; skin tests, and other alternatives
  • Screening Tests for RA: RA factor measures the level of IgM antibodies against the IgG portion of the IgG antibody. RA factor is not specific to RA and may be found in other conditions.
  • Tests of Immunocompetence:
    • Serum immunoglobulins
    • Total lymphocyte counts
    • Lymphocyte subsets (CD receptors)
    • Various WBC function assays

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Immunopharmacology Lecture Notes PDF

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Test your knowledge on the key concepts of cell mediated immunity, including the roles of T-cells, antibodies, and immune responses. This quiz covers various aspects such as the functions of CD4 Helper T-cells and techniques like ELISA. Perfect for students in immunology courses!

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