Introduction

Immunological memory:

The two arms of the adaptive immune system. (Overview slide from Shenshen Wang, UCLA).

  Antibody-mediated immunity   &  T-cell mediated immunity  from Blaussen videos.

Affinity Maturation; generation of antibodies by B cells.

T cells recognize (self) cells harboring pathogen:

Antigen presenting cells (APCs) internally process self and foreign proteins, cut them to short peptides (8-15 amino acids).

The peptides are presented on APC surface, attached to protein MHC.

T cell receptors (TCRs) recognize pathogen peptides by binding to them strongly.

T cell receoptors (TCRs) must be

Self-tolerant: to avoid auto-immune diseases

Diverse: to recognize an evolving landscape of pathogens [V(D)J recombination] (combinatorics) (video)

Specific: to lock on specific pathogens

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Immunological Tolerance:

The ensemble of T cells is shaped in the thymus gland,

where a diverse repertoire of thymocites (expressing distinct TCRs, produced by random recombination)

is culled by encounters with self-pMHC, via

Positive selection: TCR must bind sufficiently strongly to at least one self pMHC

(implicated in MHC restriction, and sensitivity).

Negative selection: TCR must not bind any self pMHC too strongly 

(deleting autoimmune TCR).

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