B1 viral replication Flashcards
What is immunosuppression?
The dampening down, full or partial suppression of the immune response, either naturally or through deliberate intervention.
What are some conditions that require immunosuppression?
Autoimmune diseases (RA, SLE, Crohn’s), allergies (asthma, hay fever), organ transplantation, GVHD.
. What are the six main ways to suppress the immune system?
Corticosteroids
Cytotoxic drugs
Non-cytotoxic drugs
Trapping activated T cells
Antibodies
Radiation
What are corticosteroids?
Steroid hormones that are powerful anti-inflammatory and immunosuppressive agents.
Where are corticosteroids naturally produced?
In the adrenal gland.
What are the two main classes of corticosteroids?
Glucocorticoids and mineralocorticoids.
What is the natural glucocorticoid derivative?
Cortisol.
What is prednisone?
A widely used synthetic corticosteroid that is a pro-drug converted into prednisolone in the liver.
How do corticosteroids work?
They bind to cytoplasmic steroid receptors, enter the nucleus, and activate transcription of anti-inflammatory genes.
What are the effects of corticosteroids?
Reduction in CD4+ T cells, decreased macrophage activation, and inhibition of mast cell degranulation.
What are some clinical uses of corticosteroids?
Treatment of autoimmune diseases (RA, SLE), allergies (asthma), inflammatory diseases (Crohn’s), and preventing allograft rejection.
What are common side effects of corticosteroids?
Weight gain, osteoporosis, mood swings, cataracts, hypertension, and increased infection risk.
What are cytotoxic drugs?
Drugs that kill dividing cells by targeting DNA synthesis.
What are examples of cytotoxic drugs?
Cyclophosphamide, methotrexate, mycophenolate mofetil, leflunomide, azathioprine.
What are the limitations of cytotoxic drugs?
They are non-specific and affect all rapidly dividing cells, leading to toxicity.
What are the main uses of cytotoxic drugs?
Cancer treatment, autoimmune disease management, and preparation for bone marrow transplant.
How does cyclophosphamide work?
It alkylates DNA, preventing replication and inducing cell death.
What are the side effects of cyclophosphamide?
Bone marrow suppression, alopecia, bladder irritation, sterility, and teratogenic effects.
How does methotrexate work?
It inhibits dihydrofolate reductase (DHFR), blocking purine synthesis and T-cell apoptosis.
What are the uses of methotrexate?
RA, psoriasis, Crohn’s disease, and some cancers.
How does mycophenolate mofetil work?
It inhibits inosine monophosphate dehydrogenase (IMPDH), blocking purine synthesis in T and B cells.
What are the uses of mycophenolate mofetil?
Kidney transplant prophylaxis and autoimmune diseases (SLE, nephritis, uveitis).
How does leflunomide work?
It inhibits dihydroorotate dehydrogenase (DHODH), blocking pyrimidine synthesis needed by T cells.
What are the side effects of leflunomide?
Severe hepatotoxicity (especially with methotrexate) and teratogenic effects.
What are non-cytotoxic drugs?
Drugs that do not kill cells but specifically target T-cell signalling.
What are examples of non-cytotoxic drugs?
Drugs that do not kill cells but specifically target T-cell signalling.
What are examples of non-cytotoxic drugs?
Cyclosporin A, Tacrolimus (FK506), and Sirolimus (Rapamycin).
How do cyclosporin A and tacrolimus work?
They bind to intracellular proteins, forming a complex that inhibits calcineurin, blocking IL-2 production and T-cell activation.
How does Sirolimus (Rapamycin) work?
It binds to FKBP and inhibits mTOR, blocking cytokine signal transduction and T-cell proliferation.
What is the role of S1P in T-cell migration?
Sphingosine 1-phosphate (S1P) helps T cells exit lymph nodes into circulation.
How does Fingolimod (FTY720) work?
It binds to S1PR1, trapping T cells in lymph nodes and preventing them from reaching target tissues.
What is Fingolimod used for?
Treatment of multiple sclerosis.
What are the side effects of Fingolimod?
Headache, colds, nausea, heart rate changes, and macular oedema.
What are polyclonal antibodies?
Antibodies derived from animal sera (horse/rabbit) that deplete T cells via complement-mediated lysis.
What is a major issue with polyclonal antibodies?
Batch variations and risk of anaphylaxis.
What are monoclonal antibodies?
Engineered antibodies targeting specific immune components, reducing unwanted immune responses.
What is OKT3 (Muromonab)?
A mouse-derived monoclonal antibody targeting CD3ε on T cells to prevent their activation.
What is Basiliximab?
A chimeric anti-CD25 monoclonal antibody that blocks IL-2 induced T-cell proliferation.
What is Daclizumab?
A humanised anti-CD25 monoclonal antibody used for kidney transplants and MS.
What are the risks of immunosuppression?
Opportunistic infections, increased cancer risk, and other long-term health complications.
Why are immunosuppressive drug combinations used?
To enhance effectiveness while reducing individual drug toxicity.
What is azathioprine, and how does it work?
A pro-drug converted into 6-mercaptopurine, which inhibits purine synthesis, blocking lymphocyte proliferation.
What are the main uses of azathioprine?
Preventing organ transplant rejection, treating autoimmune diseases (RA, Crohn’s, lupus).
What are the key side effects of azathioprine?
Bone marrow suppression, nausea, hepatotoxicity, increased infection risk.
What is belatacept, and how does it work?
A fusion protein (CTLA-4-Ig) that binds CD80/CD86, preventing T cell co-stimulation via CD28.
What is belatacept used for?
Preventing kidney transplant rejection as an alternative to calcineurin inhibitors.
What is rituximab, and what does it target?
A monoclonal antibody targeting CD20 on B cells, leading to B cell depletion.
What is rituximab used for?
Rheumatoid arthritis, lupus, certain lymphomas, and B cell-mediated autoimmune diseases.
What is tocilizumab, and what does it block?
A monoclonal antibody that blocks IL-6 receptors, reducing inflammation.
What is tocilizumab used for?
Rheumatoid arthritis, cytokine release syndrome, giant cell arteritis.
What is abatacept, and how does it work?
A CTLA-4-Ig fusion protein that inhibits T cell co-stimulation (similar to belatacept but used for autoimmune diseases).
What are JAK inhibitors, and how do they work?
Small molecules (e.g., tofacitinib, baricitinib) that inhibit Janus kinases (JAKs), blocking cytokine signalling and T cell activation.
What conditions are JAK inhibitors used for?
Rheumatoid arthritis, psoriasis, ulcerative colitis.
What is eculizumab, and how does it work?
A monoclonal antibody that inhibits C5, preventing complement activation.
What conditions is eculizumab used for?
Paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uremic syndrome (aHUS).
What is alemtuzumab, and what does it target?
A monoclonal antibody targeting CD52 on T and B cells, leading to profound lymphocyte depletion.
What is alemtuzumab used for?
Multiple sclerosis (MS), chronic lymphocytic leukaemia (CLL).
What are common side effects of monoclonal antibodies?
Cytokine release syndrome, infusion reactions, increased infection risk, reactivation of latent infections (e.g., TB, hepatitis B).
What is the difference between polyclonal and monoclonal antibodies?
Polyclonal antibodies: Derived from multiple B cell clones, broader target range.
→ Monoclonal antibodies: Derived from a single B cell clone, highly specific.
Why are calcineurin inhibitors (cyclosporin/tacrolimus) nephrotoxic?
They reduce renal blood flow and increase vasoconstriction, leading to kidney damage over time.
What is sirolimus (rapamycin) often used with in transplant therapy?
Used with cyclosporin/tacrolimus but at lower doses to reduce nephrotoxicity.
What is the benefit of using mycophenolate mofetil over azathioprine?
More selective for T and B cells, fewer side effects, less bone marrow suppression.
