Immunomodulators

Cyclosporine is an immunosuppressive drug that is commonly used to treat psoriasis. It works by inhibiting the activation and proliferation of T-helper cells, which play a key role in the immune response. By targeting T-helper cells, cyclosporine helps to reduce the inflammation and immune response associated with psoriasis. Macrophages, dendritic cells, plasma cells, and natural killer cells are not the main targets of cyclosporine, making T-helper cells the correct answer.

Azathioprine is an immunosuppressive drug commonly used in organ transplantation to prevent rejection. It works by inhibiting the clonal expansion of T and B lymphocytes, which are key players in the immune response. By suppressing the proliferation of these cells, azathioprine helps to dampen the immune response and reduce the risk of rejection of the transplanted kidney. This mechanism of action makes it an effective therapeutic option in patients undergoing organ transplantation.

Mycophenolate targets the purine metabolism in mature T&B cells, which leads to the prevention of T-cell proliferation. This action stops the rejection process of the renal graft. By inhibiting purine synthesis, mycophenolate suppresses the immune response by reducing the production of nucleotides required for cell division and proliferation. This ultimately prevents the activation and expansion of T-cells, which play a crucial role in graft rejection.

Mycophenolate mofetil is known to inhibit inosine monophosphate dehydrogenase (IMPDH) in the guanosine nucleotide pathway. IMPDH is an enzyme involved in the synthesis of guanosine nucleotides, which are essential for DNA and RNA synthesis. By inhibiting IMPDH, mycophenolate mofetil prevents the proliferation of lymphocytes, which are involved in transplant rejection. This inhibition ultimately leads to immunosuppression and helps prevent rejection of the transplanted kidney.

Folinic acid or leucovorin generally administered as calcium or sodium folinate (or leucovorin calcium/sodium), is an adjuvant used in cancer chemotherapy involving the drug methotrexate. It is also used in synergistic combination with the chemotherapy agent 5-fluorouracil.
MOA:
Folinic acid is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted to other reduced folic acid derivatives (e.g., tetrahydrofolate), and, thus, has vitamin activity that is equivalent to that of folic acid. However, since it does not require the action of dihydrofolate reductase for its conversion, its function as a vitamin is unaffected by inhibition of this enzyme by drugs such as methotrexate.

Folinic acid, therefore, allows for some purine/pyrimidine synthesis to occur in the presence of dihydrofolate reductase inhibition, so that some normal DNA replication and RNA transcription processes can proceed.

Folinic acid is administered at the appropriate time following methotrexate as part of a total chemotherapeutic plan, where it may "rescue" bone marrow and gastrointestinal mucosa cells from methotrexate. There is no apparent effect on preexisting methotrexate-induced nephrotoxicity.

The correct answer is Cyclosporine, azathioprine, prednisone. This combination of drugs is commonly used as immunosuppressive therapy in heart transplant patients. Cyclosporine is a calcineurin inhibitor that suppresses the immune response by inhibiting T-cell activation. Azathioprine is an antimetabolite that inhibits DNA synthesis and suppresses the proliferation of T and B cells. Prednisone is a corticosteroid that has anti-inflammatory and immunosuppressive effects. Together, these drugs help prevent rejection of the transplanted heart by suppressing the immune system.

The patient's symptoms, including rash, white plaque-like lesions in the mouth, dry eyes, hyperpigmentation, and diarrhea, are consistent with chronic graft versus host disease (GVHD) following bone marrow transplantation. Prednisone and cyclosporine are commonly used as immunosuppressive drugs to treat GVHD. Prednisone is a corticosteroid that suppresses the immune response, while cyclosporine is an immunosuppressive drug that inhibits T-cell activation. Therefore, the combination of prednisone and cyclosporine would be the most likely therapeutic treatment for this patient.

Rho(D) immune globulin works by blocking the production of maternal antibodies against Rho(D) positive erythrocytes. When a Rho(D) negative woman carries a Rho(D) positive fetus, there is a risk of sensitization, where the mother's immune system produces antibodies against the baby's blood type. Rho(D) immune globulin prevents this sensitization by binding to and blocking the Rho(D) positive antigens on fetal erythrocytes, preventing the mother from producing antibodies against them. This helps to prevent hemolytic disease of the newborn in subsequent pregnancies.

Mycophenolate mofetil is currently substituted for azathioprine in solid organ transplantation because it has significantly less adverse effects than azathioprine. This means that patients who receive mycophenolate mofetil are less likely to experience negative side effects compared to those who receive azathioprine. By using mycophenolate mofetil, the risk of complications and adverse reactions can be minimized, improving the overall outcome of the transplant procedure.

The most likely mechanism of action of prednisone in this case is the inhibition of T cell activation and proliferation. Prednisone is a corticosteroid that has immunosuppressive effects. In myasthenia gravis, T cells play a role in the autoimmune response that leads to the production of anti-acetylcholine receptor antibodies. By inhibiting T cell activation and proliferation, prednisone can help suppress the immune response and reduce the production of these antibodies, leading to an improvement in muscle strength.

The correct answer is "It neutralizes a surface protein receptor complex in T cells." Muromonab CD3 is a monoclonal antibody that specifically targets and binds to the CD3 receptor complex on the surface of T cells. By binding to this receptor complex, the drug prevents T cell activation and subsequent immune response, thereby reversing the acute allograft rejection. This mechanism of action is different from the other options, which do not specifically target T cell receptors or surface protein receptor complexes.

Infliximab is a biological agent that targets an inflammatory cytokine produced by activated macrophages and T-cells in inflamed joints. This aligns with the patient's symptoms and the high erythrocyte sedimentation rate, indicating inflammation. Methotrexate is an anti-inflammatory drug that has independent cytotoxic actions. It is often given with a folate supplement and is known to slow joint erosion. Both drugs fulfill the criteria of targeting inflammation and slowing joint erosion, making them suitable for the recommended drug regimen for this patient.

The patient's symptoms and lab results are consistent with systemic lupus erythematosus (SLE), an autoimmune disease. Prednisone is a corticosteroid commonly used in the treatment of SLE to reduce inflammation and suppress the immune response. It helps to alleviate symptoms such as fever, erythema, arthralgia, and oral ulcers. Additionally, it can help to improve kidney function by reducing inflammation and preventing further damage. Infliximab, BCG vaccine, Interferon-beta-1b, and Aldesleukin are not typically used in the therapeutic management of SLE.

The most likely causative agent for the patient's tingling sensation in his hands and peripheral edema is cyclosporine. Cyclosporine is an immunosuppressant medication commonly used in organ transplant recipients to prevent rejection. However, it can cause side effects such as hyperkalemia (high potassium levels), renal dysfunction (elevated creatinine and BUN levels), and peripheral edema. These symptoms are consistent with the patient's lab results and are known adverse effects of cyclosporine.

Chemotherapy, bone marrow transplantation, and HIV can lead to a decrease in cell numbers in the bone marrow, including neutrophils. Filgrastim and Sargramostim are drugs that stimulate the production of neutrophils, therefore increasing their count. These drugs are commonly used to treat neutropenia, a condition characterized by low levels of neutrophils in the blood.

Levamisole Antiparasitic drug that stimulates maturation/ proliferation of T cells.
It enhances T-cell mediated immune responses

Uses:
Adjunctive treatment together with 5- fluorouracil and leucovorin, (whose actions it potentiates) after surgical resection in patients with Dukes Stage C colon cancer.
Has been used in the treatment of Nephrotic Syndrome(not an FDA approved indication)

Adverse effects:
-Neutropenia, anemia, thrombocytopenia and agranulocytosis,.
-Encephalopathy associated with demyelination.

Not marketed in the US now because of the agranulocytosis However, thiscancer is very difficult to treat so this drug may still be used with permission.

1. Aldesleukin
A recombinent form of Interleukin 2 that promotes lymphoid cell differentiation into cytotoxic cells, and activates natural killer cells (NK's)
USES --- As an adjunct in metastatic renal cell carcinoma.
Recently approved for treatment of metastatic melanoma.

Treatment is associated with serious cardiovascular toxicity resulting from’ capillary leak syndrome’. This involves loss of vascular tone, leakage of plasma proteins and fluid into the extravascular space, which may result in hypotension, reduced organ perfusion and even death.

Cyclosporine and prednisone are immunosuppressive drugs commonly used in organ transplantation to prevent rejection. Cyclosporine specifically targets Th1 lymphocytes, which are a type of T lymphocyte involved in cell-mediated immunity. By inhibiting the activity of Th1 lymphocytes, the drugs prevent these cells from mounting an immune response against the transplanted kidney, reducing the risk of rejection. B lymphocytes, cytotoxic B lymphocytes, dendritic cells, and Th2 lymphocytes are not specifically targeted by these drugs in the context of organ transplantation.

Rapidly dividing B&T-lymphocytes cannot utilize the salvage pathway for purine synthesis, which means they rely on de novo purine synthesis. Mycophenolate mofetil specifically inhibits the enzyme inosine monophosphate dehydrogenase (IMPDH), which is involved in de novo purine synthesis. By inhibiting IMPDH, mycophenolate mofetil prevents the synthesis of guanosine nucleotides, ultimately inhibiting the proliferation of lymphocytes. This immunosuppressive effect helps to prolong graft survival by suppressing the immune response.

Muromonab CD3 is the correct answer because it is a drug that disrupts both activated and non-activated T lymphocyte functions. This drug is used to prevent acute graft rejection in organ transplant patients. In this case, the patient's symptoms and laboratory results indicate moderate graft rejection, so switching to Muromonab CD3 would be an appropriate treatment choice.

Muromonab-CD3 is an immunosuppressant drug given to reduce acute rejection in patients with organ transplants. It is a monoclonal antibody (mouse origin) targeted at the CD3 receptor, a membrane protein on the surface of T cells

Muromonab-CD3 is approved for the therapy of acute, glucocorticoid resistant rejection of allogeneic renal, heart and liver transplants. Unlike the monoclonal antibodies basiliximab and daclizumab, it is not approved for prophylaxis of transplant rejection.
It has also been investigated for use in treating T-cell acute lymphoblastic leukemia

Folinic acid (LEUCOVORIN) is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted to other reduced folic acid derivatives (e.g., tetrahydrofolate), and, thus, has vitamin activity that is equivalent to that of folic acid. However, since it does not require the action of dihydrofolate reductase for its conversion, its function as a vitamin is unaffected by inhibition of this enzyme by drugs such as methotrexate.

Folinic acid, therefore, allows for some purine/pyrimidine synthesis to occur in the presence of dihydrofolate reductase inhibition, so that some normal DNA replication and RNA transcription processes can proceed.

The correct answer is Anti-Scl-70. This is because the patient's history of dry eyes and mouth, along with the positive antinuclear antibody test, suggests that she may have Sjögren's syndrome. Sjögren's syndrome is commonly associated with autoimmune diseases, such as systemic sclerosis (scleroderma), which is characterized by the presence of Anti-Scl-70 antibodies. Therefore, it is likely that the patient in this case has positive Anti-Scl-70 antibodies.