Joplin Material Flashcards
What exists on naive T cells?
TCR w/ CD3 CD4/8 MHC I CD 28 LFA-1 and VLA-4 Chemokine receptors
Who can activate naive T cells?
Only DCs.
Who can activate memory T cells?
Macrophages and B cells.
Movement of T cells through the lymphoid organs:
Naive T cells enter LNs via HEVs.
T cells sample Ag processed by APCs.
T cells that do not encounter a specific Ag leave the node and travel to the next node.
LFA-1/VLA-4 on T cells binds:
ICAM-1
VLA-4 exists only on activated T cells.
Upon binding Ag to MHC, what is the next costimulatory bindings?
Expression of B7 is upregulated on APCs and binds CD28.
CD40L is upregulated on T cells and binds CD40 on APCs.
Once T cell is activated, what does it secrete?
IL-2 which binds its IL-2R and promotes T cell proliferation.
Expression of CD69 causes what?
CD69 on T cells binds to S1PR and impairs migration. To leave the LN, it can increase expression of S1PR.
Th1 proliferates in response to?
Secretes?
Novel TFs?
INF-y and IL-12
IL-2 and IFN-y
T-bet
Th2 proliferates in response to?
Secretes?
Novel TFs?
IL-4
IL-4, IL-5, IL-13
GATA-3
Th17 proliferates in response to?
Secretes?
Novel TFs?
IL-1 and IL-6.
IL-17 and IL-22
RORyt
Migration of activated Th cells
Once activated, Th cells change their chemokine receptor expression and migrate to the edge of the follicular zone.
Activated Th cells secrete low levels of cytokines and increase expression of costimulatory molecules.
Activated T cells begin expressing CTLA-4.
Treg cells proliferate in response to?
Secretes?
Novel TFs?
IL-2, TGF-beta.
IL-10 and TGF-beta
FOXp3
Memory T cells require what cytokines for survival?
IL-7 and IL-15
Memory T cells express increased levels of what?
Bcl-2
How do Treg cells temper activation?
By having their CTLA-4 bind B7 and shut down IL-2 production.
CTLA-1 is induci0ble on?
PD-1 is inducible on?
Activated T cells
T cells, B cells, and myeloid cells.
What is the major difference between effector T cells and naive T cells?
Effector T cells is able to respond to specific Ag w/o need for costimulation via B7-CD28.
How does INF-y stimulate Mo?
It stimulates MHC II and B7 expression.
This activates Mo to phagocytose and B cells to stimulate complement.
Function of Th2 in phagocyte-independent immunity:
It stimulates IgE (via class switching), MC and eosinophil reactions. IgA production. Secretes IL-4, IL-5 and IL-13
IL-13 and IL-4 activates monocyte to become:
M2, release IL-10 and TGF-beta and have anti-inflammatory efects, wound repair, etc.
TLR ligands and IFN-y activates monocyte to become:
M1, release IL-1, IL-2, IL-23 and cause inflammation.
OR
Secrete ROS, NO, enzymes to kill.
What are 2 mechanisms for cell killing by CTLs in MHC I?
Granular proteins (granzyme, perforin, etc) FasL on infected cell and Fas (CD95) on CTL.
What cytokines enhance NK cell killing?
IFN a/b and IL-12
Inhibited by MHC I
ADCC
Occurs in NKs, Mo, monocytes, neutrophils and eosinophils.
Target recognition via IgG.
Kills by lytic enzymes, TNF and perforin.
Evasion mechanism of Mycobacteria
Inhibits phagolysosome fusion.
Evasion mechanism of HSV
Inhibits Ag presentation by interfering with TAP transporter.
Evasion mechanism of CMV
Inhibition of Ag presentation by removal of MHC I from ER.
Evasion mechanism of EBV
Inhibits Ag presentation and proteosomal activity.
Evasion mechanism of Pox virus
Inhibits effector cell activation.
Receptors on naive B cells
BCR (IgM/D, Iga, Igb) CD19 CD21 CD81 MHC II CD40
B2 cells subsets
Follicular B cells - recirculating B cells.
MZ B cells - in spleen and respond to blood borne polysaccharide Ags.
Migration of B cells in LN
Enter via HEV
Migrate to primary follicle via CXCR5.
Receive signal to survive from FDC
Exit via efferent vessels.
1st signal for B cell activation
Ag recognizes mIgs.
Must crosslink 2 or more BCRs or bind C3d on Ag w/ B cell CR2 (CD25).
Migration of activated B cells in the LN
After activation in the follicular zone, B cells change their chemokine receptor expression and migrate to edge of FZ. Activated B cells secrete low levels of IgM and increase expression of costimulatory molecules and cytokine receptors. B cells are now close enough to be helped by Th cells.
After being helped by T cells:
B cells migrate back to the FZ and create a GC where they undergo class switching and affinity maturation..
Successful rearrangements are selected/supported by:
Tfh and FDCs.
Tfh function
Express ICOS that binds to ICOSL on B cells and is essential for GC reaction.
Secretes IL-2.
Provides IFN-y and IL-4 for class switching.
How does CD40:CD40L trigger isotype switching?
Increases accessibility of DNA at C region.
Induces expression of AID.
Affinity maturation
Introduces point mutations in variable areas in the Ig gene to increase the affinity of Abs (somatic hypermutation).
AID function
Converts Cs to Us and allows Ape I endonuclease to create double-standed breaks in DNA.
FDC’s role in B cell survival
FDCs provide intact Ag to interact w/ B cells. If it binds, B cell is rescued.
B-1 cells respond to:
T-independent responses in mucosal sites.
MZ B-2 cells respond to:
Blood-borne pathogens.
Plasma cells have decreaed:
CD19, CD20, MHC ii.
To act as obsonins:
Ag-bound Abs bind to Fc region.
Classical pathway of complement is activated by:
Ag + Ab (viruses and bacteria)
Alternative pathway is:
Ab independent.
C1 component of complement subunits and its cleavage
Has 1 C1q hexamer and 2 C1r and 2 C1s molecules.
C1r and C1s undergo cleavage to leave behind C1qrs complex.
Neonatal immunity
Maternal Abs (IgG) provide protection and IgA from breast milk.
