T cell memory

3: T cell response:

expansion phase = infection followed by T cell activation, differentiation and proliferation and clearance of pathogen

contraction - number of T cells reduced leaving a pool of stable memory T cells

memory

eventual second expansion

4: Memory T cell development:
clonal expansion of selected naive T cell post interaction with APC leads to differentiation into effector cells and central memory T cells. Central memory T cells differentiate into effector cells upon encountering antigen again

5: Three identified models for generation of memory T cells = linear differentiation, bifurcative differentiation and progressive differentiation
Linear = after activation by APC, effector cell transformed to memory effector, they’re able to self sustain in tissue or circulation
Bifurcative = immediately after activation naive T cell differentiates into effector, Tem (effector memory) or Tcm (central memory T cells)
Progressive = state of stem-cell like which can create all other subtypes

6: central memory cells express CCR7 and remain in peripheral lymphoid tissues after restimulation

effector memory cells mature rapidly into effector T cells after restimulation and secrete large amounts of IFN gamma, IL4 and IL5. They express CCR3 and CCR5 for inflammatory chemokines

7: There are many memory T cell subsets.
Tcm = central memory T cells
Tem = effector memory T cells
Temra = terminally differentiated effector memory T cells
Trm = resident memory T cells
Tfh = follicular helper memory T cells

Each has multiple markers, some differ between mice and humans, others are the same. Temras are only found in humans

8: Surface marker alterations occur during differentiation based on whether a T cell is an effector or memory T cell. Some markers fluctuate between functions depending on what cells they’re found on
Memory cells don’t require IL2 to keep on proliferating - don’t express CD25, Tregs don’t compete with memory cells

9: Each activation of memory B cells increases affinity whereas the affinity of T cell for antigen doesn’t change with subsequent exposures. B cell V region continues to mutate in B cells whereas in T cells they remain the same in memory cells.

11: Many different vaccines used over past 200 years, generally successful at preventing very serious disease - vaccines not designed for non-life threatening diseases.
Some diseases change and evolve meaning they require new vaccines eg malaria

12: Goal of vaccination is to induce memory prior to infection with infectious agent. Vaccines do this in different ways
Cowpox extract vaccination is a T cell vaccine stimulating help for B cells and antibody production.
TB vaccine also a T cell vaccine promoting help for macrophages by IFN gamma production inducing M1 phenotype attraction
Various vaccines against viruses work by stimulating T or B cells causing production of neutralising antibodies and CD8+ killing of infected cells.
Bacterial polysaccharide vaccines are T independent and stimulate production of neutralising antibodies and complement killing (opsonisation)

13: Different types of vaccines, may be live attenuated, dead/inactive variant, toxins produced by pathogen, subunits, RNA or DNA etc

15: SARS-CoV2 memory formation:

  1. SARS-CoV-2 infection

  2. innate response (DC activation and uptake of viral antigens)

  3. adaptive immunity induced - Th cytokine production, Treg inflammation regulation, CTLs kill infected cells and Tfh induce antibody production

  4. memory T and B cells

16: Much lower cells of CD27+ cells in patients who died of SARS-CoV2 or were infected compared with healthy individuals. Recovering individuals had good levels of CD27+ cells

17: Recovery from SARS CoV2 results in doubling of CD27+ cells
memory creation from vaccine = 2 weeks after

18: SARS-CoV2 specific CD4+ T cells predominantly Tcm cells

19: SARS CoV2 infection consists of initial B and T cell response with memory T and B cells present, found by analysing UK population who had recovered
Had memory for at least 8 months after infection, need booster to prevent waning and also because virus keeps changing so need new ones

extra reading required:

  • central vs effector memory