Chapter 8 - T cell mediated Immunity Flashcards
challenge of immune system upon infection
there are only a small fraction of specific T cells in the blood
result of pathogens meeting T cells
must produce an expanded effector T cell population primed to fight infection but is self tolerant
dendritic ells are essential
activators of the adaptive immune system
dendritic cells bring pathogen antigens to
secondary lymphoid tissue
Macrophages major function
defense and repair of tissues
dendritic cells major functions
trigger T cell responses
dendritic cells in peripheral tissues vs lymphoid tissues
peripheral - extensive phagocytosis
lymphoid - presentation of peptide:MHC to T cells
when dendritic cells are in lymphoid circulation
phagocytosis is topped
MHC molecules move out to surface
macropinocytosis
nonspecific ingestion of large amounts of extracellular fluid signals for dendritic cells maturation and migration
ways dendritic cells present antigens
receptor mediated endocytosis
macropinocytosis
viral infection
cross presentation
TLR signaling increases efficiency of
MHC class II presentation of peptides
chemokine induce
migration to secondary lymphoid tissue
2 phases of T cell migration
migration of naive T cells from blood to secondary lymphoid tissues
migration of activated T cells from secondary lymphoid to peripheral tissues
what happens to T cells that encounter specific antigen?
what happens if they don’t?
if they do - they proliferate and differentiate into effector cells
if they don’t - they leave the node in the efferent lymph
naive T cells recirculate through ______________ tissues through either _______________ or _______________
secondary lymphoid
blood
afferent lymph
direct route of naive T cells
migrations to draining lymph node via blood
indirect route of naive T cells
did not encounter antigen in one lymph node but traveled to draining lymph node and found it there
homing of T cells to 2o lymphoid tissue
using receptors to follow concentration gradient (chemokine) on HEV cells
initial contact induces interactions between other adhesion moleules
homing of T cells to 2o lymphoid tissue is similar to
neutrophils
T cell interaction is necessary to _________ the T cell so that it can become a _________________
prime
effector T cell
in the lymph node, T cells survey __________________ on dendritic cells via _________________
peptide:MHC complexes
transient contacts
interaction between dendritic cell and T cell lasts
several days
when a T cell proliferates and differentiates, is it still bound to dendritic cells?
YES
conjugate pair
tight binding of dendritic cel and T cell via specific peptide MHC complex
costimulation
necessary for proliferation and differentiation of naive T cells into mature effector T cells
what is required for naive T cell activation?
costimulation by B7 to CD28
signal 1 of costimulation
peptide:MHC
signal 2 of costimulation
b7 and CD28
signal 1 and signal 2 must be delivered ___________ by a single APC
simultaneously
is costimulation delivered by multiple cell types?
NO
only professional APCs
B7 is not expressed on APC in
absence of infection
B7 expression is induced by
signaling from TLR
other innate immune receptors
if a T cell only receives one signal, the T cell becomes
anergic
naive T cells are activated inly when
innate immune system senses infection
only in the ______________ will a dendritic cell be able to activate a naive T cell
presence of infection
CTLA4
expressed by activated T cell later in immune response
regulates T cell response, prevents tissue damage
Binding of B7 to _____________ prevents ___________ of T cells
CTLA4
overstimulation
ITAM
immunoreceptor tyrosine based activation motif
Muromonab CD3, Otelixumab
targets CD3
suppress T cell reactions in transplant rejections, autoimmune diabetes
Immunological synapse
clustered TCR, MHC, coreceptor
NFAT
nuclear factor of activated T cells
goes into nucleus –> activates transcription of genes to activate T cells
TCR binding and costimulation activate
IL-2 gene expression
signal 1 of costimulation in relation to IL-2
induces NFAT to activate IL-2 tanscription
signal 2 of costimulation in relation to IL-2
stabilizes IL-2 mRNA –> increases rate of IL-2 transcription
IL-2 induces
T cell proliferation
how does IL-2 signal?
autocrine signaling
many cytokines that stimulate T cells activate what pathway?
JAX-STAT pathway
JAX-STAT pathway
invalid in IL-2 signaling
Tofacitnib (Xeljanz) and Upadacitinib (RINVOQ)
oral small molecule JAK inhibitor, prevent activation of JAKs and STATs
rheumatoid arthritis and ulcerative colitis
activate of effector T cell changes
expression of cell adhesion molecules
switching from L-selectin to ___________ allows T cells to ___________________
VLA-4
fight infection in the periphery
is VLA-4 found in resting CD4 T cells?
why?
NO only activated
it is for infected tissue homing
VLA-4
directs migration to infected tissue
binds VCAM-1 on activated endothelium
allows T cells to home to sites of inflammation and infection
effector function are
different ways in which T cell directly destroys pathogen or helps other cells eliminate it
Th1
leave lymphoid tissue
helps macrophages
CD4
induce inflammation
Th17
leave lymphoid tissue
recruits neutrophils
CD4
CXCL8 production
Th2
leave lymphoid tissue
eliminate parasites
CD4
IgE production
TFH
remain in lymphoid
helps B cells
CD4
Isotype switching
Treg
circulate in periphery, suppress
CD4
inhibit inflammation
CTL
leave lymphoid tissue and kill infected cells
CD8
Recognition of naive T cell needs ___ & ____ for activation
MHC:peptide
costimulation
Effector function of T cells needs ___ for activation
MHC:peptide ONLY
NO COSTIMULATION
APC can stimulate effector T cells
WITHOUT costimulation
IFN-gamma
inhibits viral replication
increases processing and presentation
CD8 cells cytotoxins
Perforin
Granzymes
Granulysin
Serglycin
Th1 cells cytokines
IFN-gamma
Th2 cells cytokines
IL-4
Th17 cells cytokines
IL-17
Tfh cells cytokines
IL-21
IL-4
Treg cells cytokines
TGF-beta
Effector function of activated CD8 T cells
Kill infected host cells
What triggers polarized release of lytic granules to target?
Binding of TCR on CD8 T cells
Pathways of inducing apoptosis in target cell
- Make pores in membrane –> deliver cytotoxins
- Fas-ligand on T cell binds Fas on target
Necrotic vs. Apoptotic cells
Necrotic: fragmented membrane, components spill out
Apoptotic: intact membrane, components condensed and don’t spill out
Why are CD8 cells serial killers?
CTL resynthesizes lytic granules so it is able to kill more than one target cell
Difference between CD8 T cells and neutrophils
CD8 can kill many cells
Neutrophils die after killing one
Effector functions of activated CD4 T cells
-Help macrophages and B cells
-Improve neutrophil response
-Stimulate parasite response
-Suppress T cell response
Th1 Response
Cell-mediated immunity
Dominated by effector cell activation
Th2 Response
Humoral immunity
Dominated by antibodies
Differentiation of CD4 T cells depends on
Nature of pathogen
Tissue of origin of dendritic cell
Innate immune response
Help that Th1 cells give macrophages
CD40 ligand expression on T cell
IFNg secretion by T cell
How do Th2 cells remove parasites?
IgE production forms bridges between eosinophils and parasites
Eosinophil releases toxins that kill
Help that Tfh cells give B cells
CD40 ligand expression on T cell
T cell secretion of IL-4, IL-21
How do Th17 cells recruit neutrophils?
Stimulate IL-8 production which recruits neutrophils
Treg mechanism of suppression
- prevent dendritic cells from interacting
- directly inhibit effector T cells
Treg characteristics
High CD25 expression
Express FoxP3
TGF-beta
Problem of too many Treg cells
Exacerbated hepatitis B infection or tuberculosis
