Searching in immunology

T cells in LN (no infection)

A. Peixoto, Harvard Medical School 		Neutrophils in LN (with infection)
Chtanova et al, Immunity 2008.

How T cells search

Random walk models:

Vary parameters $\rightarrow$ how long does it take to find target?

Problems:

  1. Can cells tune speed and persistence independently?
  2. Is behavior cell-intrinsic, or shaped by environment?

Migration: Act model

Cells move if we add positive feedback on protrusive activity ($\approx$ actin polymerization)1:

Parameters:
λact$\approx$ protrusive force
maxact$\approx$ polymerized actin lifetime

1Niculescu et al. PLoS Computational Biology, 2015.

"Optimal" searching in a realistic model

Evolution:

  1. Start with low λact / maxact
  2. Cells proliferate and mutate λact / maxact
  3. Survival of the "fittest" : cells that cover the most ground (without breaking apart)
  4. How do average parameters change over generations?.

"Optimal" searching in a realistic model