T Cell Development and Effector Function Flashcards
T Cell Receptor
V (D) J recombination uses RAG proteins V region has 3 hypervariable regions TCR remains membrane bound non class switching or affinity maturation** majority alpha beta
smaller subset of T Cell Receptors?
gamma-delta
**only 5-10%
why is it important to have no affinity maturation in T Cell receptor?
increases the likelihood they will recognize a self peptide
this could lead to autoimmunity
what does the TCR recognize?
1-3 residues on the MHC-peptide complex
much weaker interaction than with antibodies
what is necessary for TCR binding?
binding to both the antigen and the MHC molecule
beta chain locus for TCR?
on chromosome 7
includes D regions
**undergo combinatorial and junctional diversity
RAG1 and RAG 2 proteins mediate recombination
double negative cell
naive mature T cell that does not express the CD4 or the CD8
double positive cell
express both CD4 and CD8 on the cell
what will express CD4?
something that interacted with MHC II
wha will express CD8?
something that interacted with MHC I
what T cells make it to the periphery
those that had weak affinity for MHC and self antigens
positive selection
weak interacting TCRs with antigen/MHC are selected to survive
negative selection
strong interacting TCRs with antigen/MHC are selected against and undergo apoptosis
where does positive and negative selection occur
cortex
as maturing T cell moves to the medulla what happens?
becomes single positive
MHC restriction
TCR only recognizes an antigen bound to MHC
what happens if you can’t express MHC class I
will only have CD4 (no CD8 expression)
cell-mediated immunity involves what to processes?
combats intracellular microbes (ingested microbes and viruses
T cells recognize peptides presented in the context of MHC (APC’s and infected host cells)
APCs express what MHC?
MHC class II (also Class I)
what cells express MHC class I?
all nucleated cells
what happens when naive CD4 cells are activated?
change their IL-2 receptor to higher affinity
can undergo clonal expansion and mature to effector or memory CD4 T cells
what do you need to make sure if you remove a patient’s spleen?
that they are up to date on their immunizations
what makes up the TCR complex?
CD3, zeta chain, and TCR
on all the T cells
CD28
interacts with B7 molecules on APC
this increases IL-2 production
activate the T cell
after T cells have been activated, the CTLA-4 is increased - inhibitory structure
CTLA-4
outcompetes the CD28 and decreases IL-2 production
cross-presentation
dendritic cell can place antigens on MHC class I and II
CD4 secretes cytokines that help to activate the CD8 cells
activation of CD8 T cells
can be activated directly but also by cross-presentation CD-4 cytokines
CD40L
helps to prolong the interaction of the T cell with the APC
what happens to IL-2 receptor during activation?
increases its affinity for IL-2
IL-2
survival, differentiation of the CD4 and CD8 T cells
TGF-beta
inhibition of T cell activation
IL-4
switches B cell to IgE
**Th2
IL-5
activation of eosinophils
**Th2
Interferon-gamma
activation of macrophages
what would happen after you block CTLA-4 action?
would not be able to inhibit the T cell proliferation and they would always stay on
**may be beneficial in anti-cancer therapy
side-effects: autoimmunity
types of CD4 T cells?
Th2, Th1, Th17, T regulatory cells
Th1 cells
produce IFN-gamma
activate macrophages
Th2 cells
produce IL-4, IL-5, and IL-13
promote humoral immunity
Th17 cells
produce IL-17
involved in host defense AND pathogenesis of autoimmune disease
T regulatory cells
suppress the T cell function
CD40L
on the CD4 T cells that interacts with CD40 on macrophage
leads to macrophage activation
what happens with asthma (which T cells)?
Th2 which activates eosinophils and mast cells
what activates Th1 formation?
IL-12 and IFN-gamma
what activation Th17 formation?
IL-6** TGF-beta IL-1 IL-23 GM-CSF
what activates Th2 formation?
TSLP
what do Th1 cells do?
secrete IFN-gamma
also produce TNF-alpha
what does IFN-gamme release from Th1 cells cause?
activation of macrophages
stimulation of complement binding
Class II MHC and B7 expression
what may lead to multiple sclerosis?
Th1 response
what does the classical macrophage activation lead to?
enhance microbial killing
what do Th2 cells release?
IL-4, IL-5, and IL-13
IL-4
- activate B cells to produce IgE
- also activate the macrophage to increase fibrosis/tissue repair (alternative)
IL-5
activate eosinophils
alternative macrophage activation?
leads to fibrosis and tissue repair
**stimulated by IL-4 and IL-13
Th17
secretes IL-17
IL-17
recruits the leukocytes to sites of infection
functions to maintain epithelial barrier and important in gut tolerance
phagocyte with ingested microbes causes what?
MHC class II presented antigens activates Th1 and Th17 CD4 T cells
infected cell with cytoplasm microbes causes what?
MHC class presented antigens activates the CD8 T cells
what adhesion molecules move T cells to the lymph node?
expression of L selectin and LFA-1 and CCR7 on naive T cells
what adhesion molecules move T cells to sites of infection?
E and P selectin, LFA-1 and VLA-4 and CXCR3 (chemokines)
** T cells get to where they need by homing signals
what activates a naive CD4 cell to become Th1?
IL-12
dependent on antigen-recognition
basis for delayed-type hypersensitivity reaction
macrophage activation by Th1 cells?
increases ROS and NO, secretes cytokines TNF, IL-1, IL-12, increased MHC and B7
PPD test?
example of a Delayed-type hypersensitivity reaction of the Th1 activation
balance between the Th1 and Th2 cells?
Th2 cell cytokines shuts down the classical activation of macrophages (microbicidal)
defects in either can cause problems
ex/ leprosy
what happens with CD8 T cell activation?
secretion of granzymes and perforins
perforins poke holes and granzymes enter and activate the caspases > apoptosis
cooperation between the CD4 and CD8?
yeah.
