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immunological memory

Function: - a mechanism to protect us against reinfection [2] Physiology: - naive B-cells interact with T-cells in the presence antigens presented to T-cells by dendritic cells within lymphoid tissue to become activated B-cells [2] - the activated B-cells form germinal centers, proliferate & change antibody class & transform into early plasmablasts producing low-affinity antibody (IgM) - some of the proliferating activated B-cells will become memory B-cells - within the germinal center iterative cycles of proliferation, mutation & selection result in affinity maturation with increased antigen affinity of B-cell receptors - throughout this response, some B-cells will differentiate into short-lived plasmablasts, long-lived plasmablasts & memory B-cells. - upon recall, if plasma cell-derived antibodies are insufficient for protection, memory B-cell at all phases of development can rapidly differentiate into plasmablasts or initiate secondary germinal center responses in conjuction with follicular helper memory T-cells - B-cell mutation & selection in the germinal center provides a mechanism to counteract pathogen mutation - long-lived plasma cells produced in the germinal center response live in the gut, spleen, & bone marrow where they can survive for years to decades, continuously secreting antibodies independent of pathogen presence - circulating antibodies will be protective as long as the amount is sufficient to neutralize a pathogen inoculum - in contrast to plasma cells, memory B-cells recirculate throughout the body & can be rapidly activated following reinfection to produce antibody-secreting plasmablasts or initiate secondary germinal center responses - memory B-cells can respond to variants because they have a broader spectrum of affinity than is present in the antibodies secreted in response to the initial infection - secondary germinal center responses drive production of new high-affinity antibody- producing plasmablasts specific to the new challenge - emerging Covid-19 variants remain susceptible to memory T-cell responses [5] - follicular helper memory T-cells also enhance secondary antibody response - the T-cells recognize pathogen protein determinants mostly distinct from the antibody recognition site - distinct recognition by B-cells & helper T-cells of the same pathogen promotes breadth & flexibility, & provides a check on inappropriate immune responses [2] - immune memory blocks future infections either by continued production of neutralizing antibodies from long-lived plasma cells or by recalling memory B-cells & memory T-cells to rapidly produce new plasmablasts & thus restore high-affinity, neutralizing antibodies in circulation. Pathology: - memory B-cells against SARS-CoV2 spike protein increase between 1 & 8 months after Covid-19 infection [3] - IgG type most common memory B-cell with lesser IgA type - memory T-cells CD4(+) & CD8(+) decline after Covid-19 infection with a 1/2life of 3-5 months (though the role of CD4(+) T-cells may occur largely within germinal centers) - two mRNA vaccinations induce memory B-cells & T-cells that when stimulated by infection with SARS CoV2 alpha, beta or delta variants, produced neutralizing antibodies against those variants [4] - CD4+ & CD8+ memory T-cells produced - memory B-cells & T-cells remained at high levels for at least 6 months [4]

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memory B lymphocyte

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memory

References

  1. Kelly DF et al, Immunological memory: The role of B cells in long-term production against invasive bacterial pathogens. JAMA 2005; 294:3019
  2. Quast I, Tarlist B cell memory: understanding COVID-19. Immunity. 2021 Feb 9; 54(2): 205-210 PMID: 33513337 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826135/
  3. Dan JM, Mateus J, Kato Y et al Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science 05 Feb 2021: Vol. 371, Issue 6529, eabf4063 PMID: 33408181 Free PMC article. https://science.sciencemag.org/content/371/6529/eabf4063
  4. Goel RR, Painter MM, Apostolidis SA et al. mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern. Science 2021 Dec 3; 374:abm0829 PMID: 34648302 https://www.science.org/doi/10.1126/science.abm0829
  5. Ledford H 'Killer' immune cells still recognize Omicron variant Nature News. Jan 11, 2022 https://www.nature.com/articles/d41586-022-00063-0