Week 4 Diebel Flashcards
L - selectin and CCR7
hone and bind in lymph node. High in NAIVE T CELL and low in EFFECTOR CTL
IL-2R (CD25)
Binds IL-2. Low in naive t cell and HIGH in effector CTL
CD44 and LFA-1
home and bind in inflammation
low levels in naive CTL and HIGH in effector CTL
Naive t cell surface
does NOT produce IL2 or cd25
cd3, cd8 and cd25
ACTIVATED effector CTL
if cd25 -, than it is naive CTL
CD40L
present on th1
sends IFN gamma TOWARDS APC to release IL12
IL12
cytokine to induce CD8 to effector
CD25 naive vs effector
naive: only alpha chain. Low affinity for IL2
effector: alpha, beta and gamma chain. HIGH affinity for IL2
TCR-cd3 complex
found on CTL and binds mhc1 on target cells
LFA1
found on CTL and binds ICAM on TARGETS CELLS AT SITE OF INFLAMMATION. Converts to high affinity for short period of time to hold cell and than leaves 5-10 minutes later
Perforin
released by CTL to form pore in target cell (similar to C9)
Granzymes
released by CTL which enter cell and activate apoptosis
WORKS ON BID AND/OR CASPASE PATHWAY TO APOPTOSIS INFECTED CELL
Fas ligant
Is on the CTL
Activates Fas receptor in target cel and triggers apoptosis by cleavage of caspases
Activates CASPASE 8, goes to bid, release ctyo C from nito, activate caspare 9
KNOW WORKS ON BID OR CASPASE PATHWAY TO LEAD TO CELL DEATH
TNF killing?
CTL can release TNF to kill infected cells
CD2
Found on CTL
Binds to LFA3 on target cell
NK Stimulators
ifn a, ifn b, ifn gamma, TNF alpha, IL15
CD56 low
90% of blood NK cells. Unique to NK.
Most effective killers
CD56 high
10% of blood NK cells. Unique to NK.
Release cytokines. Major is IFN gamma
No granules
NK triggering?
looking for LACK OF MHC and STRESS RESPONSE
NK release of IFN gamma when lack MHC
tilt to th1 inhibit th2 induce il12 from macrophages make macrophages to become M1 Stimulate other NK cells in the environment
NK vs CTL differences
NK express CD16
no rearrangement or education
No co receptor binding needed for NK when binding MHC (to recognize)
NK vs CTL similarities
BOTH express FasL
Both release perforin and granzyme
Both express and release TNF
CD94 - NKG2A
NK receptor
High affinity BINDS HLA-E Inhibitory signal trumps any activation signal if bound DONT KILL CELL
NKG2 family
NK receptor
BINDS TO MHC
Specifically, BINDS HLA-E with high affinity
Mostly activating
Immunoglobin like receptors
KIR = killer cell immunoglobulin like receptors
BIND to MHC 1 (binds classical ones) HLA-A,B,C
Mostly inhibitory
Lectin like receptor structure
CD94 bound to NKG2A, NKG2C, etc
heterodimer complex (nkg2d is homodimer)
Most are activating, unless NKG2A which TRUMPS all and INHIBITS
HLA leave ER?
can only escape ER if it has peptide loaded
HLA-E and leader peptide
leave ER, and binds CD94/NKG2A (on NK) and says LEAVE CELL ALONE
NKG2D on NK cells
Binds MHC1 which are made when:
Activator and recognizes stress ligands on target cells
Made in oxidate stress, mass proliferation, viral infection. (ACTIVATING LIGANDS)
Ligand is ULBP and MICA/B
activating TO KILL THE CELL IF NKG2A is not bound
Stress activating signal + inhibitory signal bound to MHC1
No death
Activating stress signal and NO MHC1 present
Death
KIR
killer cell immunoglobin like receptor
MOSTLY INHIBITORY. DONT KILL CELL
Antibody dependant cell mediated cytotoxicity ADCC
all bind ot Fc receptor macro, neutro and eosin kill by cytolytic enzyme TNF release by NK mono and macro Perforin release by eosin and NK granzyme release by NK
Licensing system
APC licensed by TH1 or TH17 if want to go on to activate CD8
PAMP and TLR can license APC
CTL-P activated by LICENSED APC
1. TCR and MHC1 on licensed APC
2. CD28: cd80/86
3. Il2 secreted by th1/17 to activate CTL
characterisitcs of DENDRITIC
- endo or phagocytosis
- activated by pattern recognition receptor
- increases mhc2 once in lymph
- normally have cd80/86
mhc2 and cd increase when become mature dendritic - activates naive, effector and memory
characteristics of MACRO
- phagocytosis
- activated by pattern recognition receptor, and by tcell.
- must be activated to express cd80/86 and mhc2
- activates effector and memory
characteristics of bcell
- always presenting mhc2
- need activation to express co stimulatory molecules cd80/86
- present soluble antigens
tap1 / tap 2
transporter associated with antigen processing
Transports peptides from CYTOSOLIC pathway to RER
High affinity for 8-16 long amino acids
ERAAP
ER associated aminopeptidase
cleaves peptide to 9AA to fit best in MHC1
Calnexin
Holds MHC clas 1 alpha chain and ensures proper folding. Once b2 micro binds, calnexin releases the MHC1
Invariant chain(CD74)
bound to MHC2 when it leaves golgi. helps fold it and hlep transport to the cytoplasmic vesicles (MHC2 plus invariant is trimer).
CLIP
Small fragment of invariant chain left over after proteolytic cleavage takes place (class 2 assocaited invariant chain peptide)
HLA-DO
expressed only in b cells and thymus. block exchange of clip and peptide
HLA-DM
Promotes exchange between clip and peptide to allow expression on cell surface
CD8 decrease from low MHC1
4 years or later before problems, probably cd8 loss. Prone to URI from bacteria due to repeat viral infection. Would die if didnt have some help form CD4.
CD4 levels fine if MHc2 works
CD4 loss
Seen very early, maybe even loss of life. Inviable
Normal ratio of cd4:cd8
2 to 1
Ratio of cd4:cd8 in MHC1 problem
Much higher CD4 count
Lymphocyte range should be normal
relation of low MHC1 and low CD8
as t cell mature in thymus, they have both cd4 and cd8. If only 1% of mhc1 present, most t cells are maturing will be cd4 because not enough mhc1 present to stimulate maturing of cd8
Cause of MHC1 defect
Lacking promoting enzyme to activate transciption, cant transport mhc1 to surface* Problem in TAP complex was problem in example
NK and low MHC1 relation
NK would be high due to low MHC1 and stress signal
MHC2 defiency cd4:cd8 ratio
1:3. CD8 levels will be normal but CD4 very low.
MHC2 defiency blood levels
HIGH neutrophils and LOW lymphocytes.
Hypogammaglobulinemia as well
MHC2 defiency presentation
Auto recessive trait
health problems VERY EARLY IN LIFE. Mild form of SCID. SCID would have low T cell as well
treatment for MHC2 defiency
hematopoietic stem cell transplantation
Cause of MHC2 defiency
Defects in transcription factors required for expression of MHC2
RAG1/ RAG2 and Tdt
Expressed in early Pro-bell (heavy chain) and light chain (small pre-bcell)
Late pro-bcell to memory cell expresses:
CD19, 20 and CD40
Expressed B cell development stem cell to early pro-bcell
CD34 and c-kit
Immunoglobubin expression
Pre-bcell to plasma
CD79A AND B expressed:
early pro-bcell to memory cell
Major cytokines for bcell development
IL7 help from common lymph to b cell lineage
B-lymphocyte stimulator (using BR3 receptor) helps b cell survive
IL4, IL3 and low molecular weight b cell growth factor help differentiate
B1 B cell
t-independant activation
no memory
CAN replenish. normal bcell cannot
TI-1 antigen
bacterial cell wall components
LPS
(many are PAMPS)
activate B1 B cell
TI-2 antigen
large polysaccharides with repeating antigents (dextran, flagellin, polio)
binds by crosslinking BCR
-activate B1 B cell
b cell response to TI-1
TLR4 (polyclonal activation) or BCR (clonal activation)
PRODUCE IgM ONLY
B cell response to TI-2
IgM stimulation cd4 can help class switch
Tcell CD44
required to localize to thymus. not found later on in subscapsular cortex
c-kit tcell
always present but low in final steps. Required for REPLICATION
t cell CD25 (IL-2R)
required for IL-2 driven replication
