Lecture 17 Flashcards
(14 cards)
How long does immunological memory last? (smallpox vaccination example)
antibody levels have early peak, then rapid decay, followed by long-term maintenance with minimal decay
CD4/CD8 T cell memory is long lived, gradual decay with longer half-life for CD8 T cells
what are some features of memory T cells?
number is 10-100x naive precursors
not restricted to searching in secondary lymphoid tissues
proliferate more rapidly, robustly in response to same antigen dose, more rapidly display heightened effector responses
How do we detect antigen-specific memory cells?
tetramer = 4 MHC molecules w same antigenic peptide, connected to a fluorescently labeled backbone
increase avidity, allowing stable & detectable binding to antigen-specific T cells
What are the three types of memory T cells
central memory T cells: circulate in blood and lymphoid organs, encounter same antigens in lymphoid organs, mount stronger responses
effector memory T cells: circulate btwn blood/tissue, rapid maturation into effector T cells
tissue-resident memory cells : do not migrate, rapid response after encountering antigen or cytokines
What is the linear model of memory T cell development
naive –> effector –> memory
What is the branching/asymmetric divison model of memory T cell development
naive –> effector or directly to memory precursors –> memory
What are the migratory patterns of Tmem cells?
TCM: blood, T cell zones of secondary lymphoid organs, lymph
TEM: nonlymphoid tissues, lymph, lymph nodes and blood, some may be just in blood/spleen
TRM: none
Why have tissue-resident memory T cells?
survey peripheral tissues for reinfection by pathogens
How do resident memory T stay in the tissues?
reexpression of CD69 –> decreased S1PR1 surface expression –> retention of cells in dermis, may induce integrin αEβ7 (CD103) which binds E-cadherin (epithelial cells) –> entry/retention of T cells in epidermis where CD8 TRM cells reside
What is a marker of T cells that become long-term survivors?
high levels of IL-7Rα
How do naive T cells survive in the periphery? How does this differ from memory cells?
require periodic stimulation w IL-7 and self antigens presented by self MHCs
memory T can be maintained by IL-7 (retained or re-expressed), less dependent on contact w self peptide:self MHC complexes for survival
What shifts in metabolism are associated with the differentiation of naive T cells into efffector/memory T cells?
naive = glycolysis
effector = glycolysis
memory = fatty acid oxidation
stable levels of oxidative phosphorylation, higher in memory
How do secondary antibody responses from memory B cells differ from the primary response?
primary: IgM > IgG, low affinity, low somatic hypermutation
secondary: IgG & IgA, high affinity, high somatic hypermutation
How does repeated immunization alter antibody production?
affinity and amount increase
IgG from mature B that undergo isotype switching/somatic hypermutation –> affinity maturation
