Dendritic cells and macrophages are the
antigen-processers for this response
ACRs of APCs present antigen fragments bound to
class II MHC molecules and B7 on their
surfaces
Th cell
TCRs bind antigen fragments and MHC-II alpha1- and
beta1-chain contact residues, while CD4 binds beta2-domain
of MHC-II
Th cells proliferate and differentiate to form large
numbers of Th and Th memory (Thm) cells
Th cellssecreteinterleukin 2 (IL-2)
which triggers proliferation of Tc cells (after they
have bound processed
antigen)
Thm cells formed are very long-lived Th cells
(half-life of ~40 years in humans) that can respond to
processed antigen to help provide a much quicker secondary
CTL response
Tc
cell TCRs bind antigen fragments and MHC-I alpha1- and
alpha2-chain contact residues, while CD8 binds
alpha2-domain of MHC-I
Tc cell CD28 binds CD80 or CD86 on target cells ... when available
(the degree to which this step is required is debatable, because not all
target cells will possess CD80 or CD86)
Tc cell expression of high-affinity IL-2 receptors is upregulated as
a result of the earlier signals and
these receptors bind IL-2 produced by Th cells (CTLs also produce some IL-2)
Tc cells proliferate and differentiate to form large
numbers of CTLs and Tc memory (Tcm) cells
CTLs kill target cells by inducing them to commit
suicide via apoptosis
Tc memory cells formed are very long-lived Tc cells
(half-life of ~40 years in humans) that can respond to
processed antigen to help provide a much quicker secondary
CTL response
CTLs induce apoptosis in target
cells
CTLs form antigen-specific conjugates with target
cells via interaction of TCRs with processed
Ag on target cell surfaces
CTLs orient their microbule organizing centers
(MTOCs) towards the bound target cell
Granules containing lytic mediators are transported
to CTL cytoplasmic membrane along microtubules
CTLs secrete granule contents onto surface of target
cell that is bound to surface of CTL, thus releasing
perforin subunits and granzymes into the
intercellular space
perforin subunits polymerize in cytoplasmic
membrane of target cell
granzymes enter target cell through pores in
centers of the hollow perforin polymers
Target cells are destroyed by conversion into
apoptotic bodies which are phagocytized and eliminated
by macrophages
Secondary Response
Tcm cells, whose numbers have increased as a result of
the primary response, are again stimulated by binding
processed endogenous antigen on target cells
Thm cells, whose numbers have also increased as a
result of the primary response, are again stimulated by
binding processed exogenous antigen on APCs
Tc proliferation and differentiation to form increased
numbers of CTLs and more Tcm cells is much faster (on the
order of ~4 days) than in the primary response, but (unlike the
secondary antibody response) does not seem to be qualitatively
different from the primary response
CTLs kill target cells in the same manner as they did
in the primary response ... by inducing apoptosis