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10 marksDrNB 2025NephrologyTransplant Immunology
a) Describe co-stimulatory pathway for T-cell activation. [5] b) Describe use of various agents acting on co-stimulatory pathway in kidney transplantation. [5]
Co-stimulatory pathways are essential secondary signals required for full T-cell activation besides antigen recognition. They prevent T-cell anergy and promote clonal expansion, cytokine production, and effector function (Harrison's 21e, Ch. 20).
T-cell activation requires two signals:
- Signal 1: T-cell receptor (TCR) recognition of antigen-MHC complex on antigen-presenting cells (APCs).
- Signal 2 (co-stimulation): Interaction between co-stimulatory molecules on APCs and T cells, necessary to avoid T-cell anergy and induce activation.
Key co-stimulatory pathways:
| Molecules Involved | Cell Type | Interaction | Function |
|---|---|---|---|
| CD80 (B7-1), CD86 (B7-2) | APCs | Bind CD28 on T cells | Positive co-stimulation — T cell activation, IL-2 production |
| CTLA-4 (CD152) | T cells | Binds CD80/CD86 with higher affinity | Negative regulation — inhibits T cell activation |
| CD40 (APCs) – CD40L (T cells) | APCs and T cells | Promotes APC activation and survival | Enhances co-stimulation, cytokine secretion |
| PD-1 (on T cells) – PD-L1/PD-L2 (on APCs) | T cells/APCs | Immune checkpoint | Inhibitory regulation of T cells |
In kidney transplantation, recipient T cells recognize donor alloantigens leading to graft rejection if co-stimulatory signals are intact. Blocking these pathways can induce tolerance (Brenner & Rector's The Kidney, 11e).
References
Brenner & Rector's The Kidney, 11eHarrison's 21e, Ch. 20Harrison's 21e, Ch. 69