Cellular Layer — How Cells Negotiate and Confirm Signals

Cells constantly exchange information, but communication is not automatic.
Instead, multi-step cellular protocols govern who gets heard, when, and how — involving receptors, co-receptors, and environment-dependent modifications.


Example 1: Plant PRR-BAK1 Complex — A Structured Handshake for Immunity

In plant innate immunity, Pattern Recognition Receptors (PRRs) detect PAMPs (Pathogen-Associated Molecular Patterns) like bacterial flagellin.
But recognition alone is not enough — co-receptor BAK1 must join for the signal to proceed, forming a multi-step handshake.

Protocol Breakdown (step-by-step):

StepAction
RecognitionFLS2 binds flg22 (PAMP) — packet reception.
NegotiationBAK1 joins only if FLS2-flg22 complex is formed — handshake validation.
ExecutionKinase cascade (BIK1, MAPKs) propagates the immune signal.
ConfirmationScaffold proteins stabilize the receptor complex.
Error handlingBIR proteins prevent false activations.

Failure Example:

  • Pathogen effectors (e.g., AvrPto) block BAK1 recruitment — handshake hijacked, immune response blocked.

Example 2: Mammalian Immune Synapse — Stepwise Confirmation to Prevent Error

T cell activation requires multiple confirmations — a complex negotiated immune protocol.

  • Recognition: TCR binds antigen on MHC.
  • Negotiation: Co-receptors (CD4 or CD8) confirm MHC type.
  • Co-stimulation: CD28 binds B7 — essential handshake.
  • Execution: Intracellular signaling (ZAP70, LAT).
  • Error handling: CTLA-4 can terminate the process if activation is inappropriate.

Failure Example:

  • If checkpoints (like CTLA-4) fail, autoimmune diseases like lupus or rheumatoid arthritis can arise — protocol breakdown.

Key Takeaways for Cellular Layer

  • Cell-cell communication is a negotiated, multi-step protocol, not a simple binding event.
  • Co-receptors and scaffolds act as protocol managers, confirming and stabilizing interactions.
  • Error handling mechanisms prevent false signaling — when these fail, disease follows.
  • Thinking in protocols explains why immune responses are specific, and how pathogens exploit these protocols to avoid detection.