Isaac Newton Institute                               SPL seminar                           4 December, 2023

Intersections of the adaptive immune response and statistical physics

Outline

I.       The adaptive immune system: B cells, T cells- diverse, self-tolerant, and specific                                       

II.      Thymic Selection: positive and negative selection, specificity from weak amino-acids, extreme value distribution

III.     Quorum sensing for peripheral tolerance, and persistent infections

IV.     B cells: Viruses, Antibodies, Antigens, and the puzzle of low HIV spike density                                    

V.      Affinity Maturation: Germinal Center, Rapid evolution of antibodies, Fisher and Price equations

VI.      Fitness & Evolution: Competition for virus capture and proliferation signal from helper T cells

VII.     Optimal density for eliciting potent antibodies; implications for nanoparticle vaccination & HIV spikes

VIII.   Broadly neutralizing Antibodies: Controlling affinity maturation against a mutable virus

IX.     Summary

 

 

 

 

 

 

 

 

 

 

Title: 
Intersections of the adaptive immune response and statistical physics
Abstract:  
The adaptive immune system protects the body from the ever-changing landscape of foreign microorganisms. The two arms of the adaptive immune system, T cells and B cells, mount specific responses to pathogens by utilizing the diversity of their receptors, generated through hypermutation.  B cells generate antibodies that strongly bind and inactivate antigens (toxic targets). Potent antibodies are generated through the process of “Affinity Maturation" which is akin to evolution at a rapid pace. T cells recognize and clear infected hosts when their highly variable receptors bind sufficiently strongly to complexes formed with antigen-derived peptides displayed on the cell surface. To avoid auto-immune responses, a process of "Thymic Selection" ensures that only self-tolerant receptors (binding weakly to self peptides) are engaged. Methods from Statistical Physics can be used to model and elucidate these processes, as will be demonstrated through selected examples.

used to model and elucidate these processes, as will be demonstrated through several examples.