Immunological memory lecture.pdf - Immunological memory Dr...

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Unformatted text preview: Immunological memory Dr. Suvas March 2017 Immune cells with memory phenotype are • Conventional CD4 T cells • Regulatory CD4 T cells • CD8 T cells • B lymphocytes T cell response to acute infection is divided into-­‐ • Priming or expansion phase • Resolution and contraction • Memory Phase But why?? Do memory T cells need interaction with self-­‐ peptide MHC complex for their survival?? Three different types of memory T cells are-­‐ Tissue-­‐resident memory cells (TRM) Effector memory (TEM) Central memory (TCM) Characteristics of memory T cells • TEM cells can migrate between tissues and secondary lymphoid tissues • TEM cells constitutive expression of some effector function • They lack the expression of CD62L and CCR7 • TCM cell reside in secondary lymphoid tissue. • They express CD62L and CCR7 • TCM have the greatest proliferative potential and can expand and differentiate upon re-­‐challenge. TRM cells are located in skin, lung and reproductive tract. They do not re-­‐enter the circulation. They express CD69 and CD103. Provide immediate protection upon local secondary infection. Generation of memory CD4 T cells • Following the resolution of infection, most infection-­‐specific effector CD4 T cells die. • Memory CD4 T cell pool decline with time and may require boosting. • It has been shown that CD4 T cells with lower expression of Ly6C and T-­‐ bet have higher probability to become memory CD4 T cell. • Memory CD4 T cells respond much faster, respond to lower antigen dose, require less co-­‐stimulation and proliferate more vigorously after re-­‐infection. • Memory CD4 T cells can reside in tissues and upon re-­‐infection, they can help to develop stronger innate immune response. • It has been suggested that memory CD4 T cell can enhance the immunogenicity of weak vaccines. Helper role of CD4 T cells-­‐ • CD4 T cells at the time of priming license DCs to activate CD8 T cells • CD4 T cell help is required to generate functional memory CD8 T cell pool • Helpless memory CD8 T cells express TRAIL upon restimulation and undergo AICD. • Foxp3 CD4 Treg cells can promote the generation of memory CD8 T cells. CD4 T cells are required for the maintenance of memory CD8 T cells. Memory B cell generation • Humoral memory is generated after infection. It is comprised of • Long lived plasma cells (first line of defense against re-­‐ infection) • Memory B cells (second line of defense rapidly get reactivated upon re-­‐infection with same pathogen) • Memory B cells can develop in response to • T cell dependent • T cell independent response Generation of T cell dependent memory B cell • Antigen activated B cells follow three fate-­‐ • Differentiate into extra-­‐follicular short lived plasma cells • Germinal center independent memory B cell • Germinal center dependent memory B cell • In pre-­‐germinal center period isotype switching occurs but no somatic hypermutation • Inside the germinal center, GC memory B cells and long lived plasma cells are generated • If the formation of conjugate between Tfh and B cell is prolonged, it will yield germinal center memory B cells. • If the duration of Tfh-­‐B cell conjugate is short it will lead to the generation of germinal center independent memory B cell. T-­‐independent memory B cell • B1 cells generate memory B cells in a T-­‐ independent manner. • B1 memory B cells are IgM+ and they reside in peritoneal cavity. Upon re-­‐infection, they need TLR signaling to differentiate into plasma cells. This process takes place in the spleen. • Memory B cells can express IgM, IgG, or IgA molecules, and upon restimulation can differentiate into plasma blasts. Unique properties of memory B cells • Stemness-­‐ IgG+ memory B cells have greater propensity to develop into plasma blasts than IgM+ memory B cells. • Reactivation of memory B cells generally require TFH cell help. TFH-­‐memory B cell interaction need MHC class II molecules. • Just like exhausted memory T cells, exhausted memory B cells are also present in humans. Their phenotype is CD27-­‐CD21low and are known as tissue-­‐like memory B cell subset. • Longevity-­‐ Maintenance of IgG+ memory B cell do not require T cells, but there is a requirement for follicular dendritic cells (FDCs). • IgM+ memory B cells can persist longer than IgG+ memory B cells • Memory B cells rapidly differentiate into plasma blasts and produce class-­‐switched antibodies. ...
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