Unformatted text preview: Immunological memory
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-‐
• 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-‐
• 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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- Winter '18