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Linkage between Innate and Adaptive Immunity (DCs to lymph node…
Linkage between
Innate and Adaptive
Immunity
DCs to lymph node
activation of conventional DCs
by pathogen recognition
(PRR & PAMP)
increased
processing of antigen
increased expression of
MHC
increased expression of
co-stimulatory molecules
increased receptors expression
towards lymphatic tissues
activated DCs travel to lymph node
(enter via
afferent lymphatics
)
activated DCs are
not phagocytic
activate
naive T cells
transfer antigen to resident DCs in lymphatic tissue
types of DCs
conventional DCs
activate T cells in lymphoid tissue
classic APC
travel to lymphoid tissue upon activation
plasmacytoid DCs
produce lots of type I IFN
secrete cytokines, amplify local response
stay at site of infection
Lymphocytes to lymph node
constantly traveling, scanning antigens
lymphocytes travel to lymph node
(enter via high endothelial venules,
HEV
)
T cell
encounter antigen
presented by DCs
stay in lymph node
activation & proliferation of T cell
effector T cell
leave via
efferent lymphatics
T cell does not encounter antigen presented by DC
leave via
efferent lymphatics
migration into lymphoid tissue
adhesion
integrin
on T cell binds to adhesion molecule
different adhesion molecules on different tissues
diapedesis (migration)
chemokines
rolling
selectin
on T cell binds to receptors
different tissues express different receptors
activation
chemokine receptor
on T cell activated by chemokines
T cell
types
CD8+ T cell
recognize Ag on
pMHC-I
effector CTLs
CD4+ helper T cell
recognize Ag on
pMHC-II
Th1
Th2
Th17
Treg
Tfh
TCR complex
TCR + CD3
ITAMs domain
recognize pMHC on APC
upon pMHC recognition
trigger
intracellular signaling
(forward & reverse)
TCR
heterodimer (𝜶 +𝜷 chain)
𝜶𝜷TCR
(main)
𝜸𝜹TCR (minor)
variable + constant region
TM protein, not secreted
clonotypic
ligand
of TCR is
pMHC
MHC
pMHC-I
endogenous peptides
activates
CD8+ T cell
MHC-I
1 𝜶 chain (TM) +
1 𝜷 microglobulin
𝜶 chain has 3 domains
constrained binding to
short Ag peptides
(8~10a.a.)
pMHC-II
exogenous peptides
activates
CD4+ T cell
MHC-II
1 𝜶 chain (TM) + 1 𝜷 chain (TM)
both have 2 domains
length
of Ag peptides bound
not constrained
general feature
allele-specific Ag peptide binding cleft
(most highly variable)
consists of
𝜶 helices + 𝜷 sheets
TM glycoprotein
several
Ig-like domains
di-sulfide bonds
to maintain 3D structure