UKPSC Prelims 2024 General Studies Paper-I · Question 85 of 147

Correct — D, Monoclonal antibodies.

A transplanted kidney is genetically foreign, so the recipient's T cells set out to destroy it. Drugs that restrain this attack are immunosuppressants, and Monoclonal antibodies belong squarely in that group.

Basiliximab, a chimeric monoclonal antibody, binds CD25, the alpha chain of the interleukin-2 receptor on activated T cells. Given around the time of surgery as induction therapy, it blunts the early T-cell response that drives acute rejection.

The historical link is even tighter. Muromonab-CD3 (OKT3), licensed in the United States in 1986, was the first monoclonal antibody approved for human therapy, and its indication was acute rejection of a transplanted kidney.

The idea to carry away: among these four classes, engineered antibodies are the one that switch T cells off rather than on. Antibiotics, vaccines and interferon serve the body's defences against infection, which is the opposite of what a graft needs.

• (a)
  Antibiotics — Antibiotics kill or inhibit bacteria; they do not act on T cells or on the rejection process. After a transplant they are given for the opposite reason, to protect a deliberately weakened immune system, for example co-trimoxazole against Pneumocystis pneumonia.

  One wrinkle: tacrolimus and sirolimus are chemically macrolides isolated from Streptomyces, and cyclosporine comes from a fungus. They are classed as immunosuppressants, not antibiotics, because restraining lymphocytes, not killing bacteria, is their use.

  Antibiotics are the right answer to a question on treating bacterial infection.

• (b)
  Vaccines — A vaccine trains the immune system to respond faster and harder to a pathogen. It is an immunostimulant, the reverse of what a graft needs.

  Patients awaiting a transplant are in fact vaccinated before surgery, and live vaccines are generally avoided afterwards precisely because the drugs have suppressed immunity.

  Vaccines are the right answer to a question on active immunisation against infectious disease.

• (c)
  Interferon — Interferons are cytokines released by cells in response to viral infection. They raise antiviral defences and activate immune cells such as macrophages and natural killer cells: immune activation, not suppression.

  In kidney-transplant recipients, interferon-alpha, once used for hepatitis C, has been associated with acute rejection, so it is avoided.

  Interferon is the right answer to a question on antiviral cytokines, or interferon-beta for multiple sclerosis.

Immunosuppression in transplantation means deliberately damping the recipient's adaptive immune response, chiefly T cells, so that a genetically foreign organ is not rejected.

Modern regimens layer mechanisms: an antibody at induction, then maintenance with a calcineurin inhibitor (tacrolimus or cyclosporine), an antiproliferative agent (mycophenolate or azathioprine) and a corticosteroid.

A monoclonal antibody is produced by a single clone of B cells (in practice a hybridoma), so every molecule is identical and binds one chosen target, such as CD25 on activated T cells.

• Basiliximab is a chimeric monoclonal antibody against CD25, the interleukin-2 receptor alpha chain on activated T cells, used as induction immunosuppression in kidney transplantation.
• Muromonab-CD3 (OKT3), approved in the United States in 1986 for acute kidney-graft rejection, was the first monoclonal antibody licensed for human therapy; it has since been withdrawn.
• Georges Köhler and César Milstein published the hybridoma method for monoclonal antibodies in 1975 and shared the 1984 Nobel Prize in Physiology or Medicine with Niels Jerne.
• Cyclosporine, a calcineurin inhibitor isolated from the fungus Tolypocladium inflatum, transformed graft survival after its introduction in the early 1980s.
• Tacrolimus, isolated from Streptomyces tsukubaensis in Japan, is another calcineurin inhibitor and is widely used for maintenance immunosuppression after kidney transplantation.
• Sirolimus (rapamycin), an mTOR inhibitor, was isolated from Streptomyces hygroscopicus in soil from Easter Island (Rapa Nui).
• Anti-thymocyte globulin is a polyclonal antibody preparation raised in rabbits or horses against human T cells, used for induction and for steroid-resistant rejection.
• Interferon-alpha has been associated with acute rejection in kidney-transplant recipients and is avoided in them; interferon-beta is a treatment for multiple sclerosis.
• Joseph Murray performed the first successful human kidney transplant in Boston in 1954 between identical twins, needing no immunosuppression; he shared the 1990 Nobel Prize in Physiology or Medicine.
• Live vaccines are generally avoided after transplantation because an immunosuppressed recipient may develop disease from the vaccine strain; inactivated vaccines can be given.
• India's Transplantation of Human Organs Act, 1994 was amended in 2011; NOTTO, under the Directorate General of Health Services, coordinates the national transplant programme.

• Reading 'antibiotic' chemically: tacrolimus and sirolimus are macrolides from Streptomyces, but the option 'Antibiotics' names a drug class defined by antibacterial use, not by chemical origin.
• Treating every antibody as protective: natural antibodies fight infection, but an engineered antibody against CD25 or CD3 disables T cells, the reverse effect.
• Confusing interferon's 'immunomodulatory' label with immunosuppression; interferons activate antiviral and cellular immunity and can precipitate rejection in graft recipients.
• Mixing up monoclonal antibodies (basiliximab, a single target) with polyclonal anti-thymocyte globulin (many T-cell targets); each is used for induction but they are distinct classes.
• Calling belatacept a monoclonal antibody: it is a CTLA-4-Ig fusion protein used for maintenance immunosuppression, not an antibody.

No eligible match among this question's citable set.

• practice — not a real PYQ

  Basiliximab, used as induction immunosuppression in kidney transplantation, acts by blocking which of the following?

  • (a)CD20 on B lymphocytes
  • (b)The alpha chain (CD25) of the interleukin-2 receptor on activated T cells
  • (c)The enzyme calcineurin
  • (d)Tumour necrosis factor-alpha
  Answerb — Basiliximab is a chimeric monoclonal antibody against CD25, so activated T cells cannot receive the interleukin-2 signal that drives their proliferation.

  CD20 (a) is the target of rituximab, an anti-B-cell antibody. Calcineurin (c) is inhibited by cyclosporine and tacrolimus, which are small molecules, not antibodies. TNF-alpha (d) is the target of infliximab and adalimumab, used in rheumatoid arthritis and Crohn's disease.

• practice — not a real PYQ

  Which one of the following drugs used to prevent rejection after kidney transplantation is a calcineurin inhibitor?

  • (a)Mycophenolate mofetil
  • (b)Tacrolimus
  • (c)Sirolimus
  • (d)Azathioprine
  Answerb — Tacrolimus binds the protein FKBP-12 and the complex inhibits calcineurin, blocking transcription of interleukin-2 in T cells; cyclosporine reaches the same enzyme through cyclophilin.

  Mycophenolate mofetil (a) inhibits inosine monophosphate dehydrogenase, starving lymphocytes of guanine nucleotides. Sirolimus (c) inhibits mTOR. Azathioprine (d) is a purine antimetabolite converted to 6-mercaptopurine. Each of the three works elsewhere in the cell.

• practice — not a real PYQ

  Consider the following statements: 1. Cyclosporine was isolated from a fungus. 2. Muromonab-CD3 (OKT3) was the first monoclonal antibody approved for therapeutic use in humans. 3. Interferon-alpha is used as a maintenance immunosuppressant after kidney transplantation. Which of the statements given above is/are correct?

  • (a)1 and 2 only
  • (b)2 and 3 only
  • (c)1 and 3 only
  • (d)1, 2 and 3
  Answera — Statement 1 is correct: cyclosporine was isolated from the fungus Tolypocladium inflatum. Statement 2 is correct: OKT3 received United States approval in 1986 as the first therapeutic monoclonal antibody.

  Statement 3 is wrong: interferon-alpha activates immunity and has been associated with acute rejection, so it is avoided in transplant recipients rather than used for maintenance. That rules out b, c and d.

• practice — not a real PYQ

  The hybridoma technique for producing monoclonal antibodies was developed by

  • (a)Georges Köhler and César Milstein
  • (b)James Watson and Francis Crick
  • (c)Joseph Murray and E. Donnall Thomas
  • (d)Frederick Banting and Charles Best
  Answera — Köhler and Milstein fused antibody-producing B cells with myeloma cells to create hybridomas, immortal cell lines that secrete a single antibody (1975).

  Watson and Crick (b) described the DNA double helix in 1953. Murray and Thomas (c) shared the 1990 Nobel Prize for organ and bone-marrow transplantation. Banting and Best (d) isolated insulin in 1921-22.

• practice — not a real PYQ

  Which one of the following vaccines is generally withheld from a person taking immunosuppressive drugs after a kidney transplant?

  • (a)Inactivated influenza vaccine
  • (b)Hepatitis B vaccine
  • (c)Measles, mumps and rubella (MMR) vaccine
  • (d)Tetanus toxoid
  Answerc — MMR is a live attenuated vaccine. In a recipient whose T cells are suppressed the vaccine strain can multiply unchecked, so live vaccines are generally withheld after transplantation.

  Inactivated influenza vaccine (a), recombinant hepatitis B vaccine (b) and tetanus toxoid (d) contain no living organism and can be given, though the antibody response may be weaker than in a healthy person.

• practice — not a real PYQ

  The National Organ and Tissue Transplant Organisation (NOTTO) functions under which one of the following?

  • (a)Directorate General of Health Services, Ministry of Health and Family Welfare
  • (b)Indian Council of Medical Research
  • (c)Department of Biotechnology
  • (d)NITI Aayog
  Answera — NOTTO was set up under the Directorate General of Health Services in the Ministry of Health and Family Welfare to coordinate organ procurement, allocation and the national registry under the Transplantation of Human Organs and Tissues Act.

  ICMR (b) funds and conducts medical research. The Department of Biotechnology (c) sits in the Ministry of Science and Technology. NITI Aayog (d) is a policy think tank, not an implementing body.