immune Flashcards
DR, DP, DQ
MHC II
T cell require (2) things for activation
- Antigen presentation
2. Co-stimulation
Alpha chain associated with B2 macro globulin
MHC-II
Made of alpha and beta chains
MHC-II
MISFOLDED PROTEIN
MHC-I
Cross presentation
Taking outside , but showing them as if they were inside . Needed to activate CD8
Activates a CD4+ T-cell
CD40 (DC)
CD40-L (T-cell)
Promotes interactions with stromal cells for development of thymocytes.
SCF and IL-7
TCR must (2)
- Interact w/ MHC
2. Not interact w/host epitope
Committed marker of double negative T-cell precursor
CD2
Once the beta portion of a T-cell is made, the T cell is
Double positive
Three things that dominate the double positive state
- Thymocyte has a functional beta chain
- Thomcyte expresses both CD8 and CD4
- Signals for rearrangement of alpha. If it cant, it will die or make delta gamma.
Pos selection
Does the T cell interact with host MHC.
If no. .. dead
Neg selection
Does the TCR recognize the epitope in the MHC molecule. The only epitope presented in the thymus are our own proteins. SO if it does recognize it, it will die.
T cell dies if
It has a strong aff for host MHC
Responds to host peptides
Naive T cells become activated in
Secondary lymphoid tissue
CD4 and CD8 help
interact with MHC for stabilization
CD3 complex and Zeta chains
signal
Three steps needed for T-cell activation
- See the epitope in the MHC
- Costimulation
- Proliferation (IL-2)
Requires for costimulation of T cells
CD28 on T cell bonds with CD80/86 (B7) on APC. If this does not happen, then T cell will become anergia or die.
Negative costimulatory molecules
CTLA-1 and PD-1
Moderate aff IL-2 receptor
beta , gamma
High aff IL-2
beta , gamma, alpha
-once CD28 interacts with CD80/86, then alpha comes in and in part of IL-2. =CD25 ,= clonal expansion.
Activation of CD8 T cells
- Naive cell interacts with DC in secondary lymphoid tissue , this requires Th cell help.
- At infected site, activated CTL recognizes a target cell displaying the correct MHC, peptide-J
- CTL is primed, by APC by CD28 and the epitope.
Prime in secondary tissue
Kill in the infected site
Expresses FOXP3
IL-10 and TGFB
Influcences IL-17
IL-23
Induces eiosinphil or Th2 activation
IL-4, IL-5, IL-13
Activates B cell and macrophages
CD40-L (on T cells)
CD40 on (B cells _
Alpha chain of IL-2 receptor
CD4/CD25
Induces germinal center formation of B-cells
IL-21 and IL-6
Memory T cells have no
CD28
Mast cells activated by
TLRs
Binding of TLR induces
NFKB
Form multi-metic complex , (1)
Cleaves to produce (2)
- NLRs
2. IL-1 and IL-18
Fever
IL-1 , IL-6, TNF
Induces pyroptosis
NLRs
Intiated when apoptosis is blocked
Necroptosis
IL-6 induces CRP to bind with
phosphocholine and acts as opsonin
INF alpha and beta binds to cytokine receptor to activate
JAK STAT
NK and macrophage for complex .. then 1. ..activates
- IL-12 and IL-15
NK cells turn into effector cells and secrete
IFN gamma
These bind to cytosolic viral dsRNA and activatates NFKB
RLRs
Activates the IRF to produce type 1 IFN
RLRs
TLR3 deficiency
impaired signaling through TLRs and IL-1R
**decrease in Type 1 IFN production .
Presents with HSV-1 encephalitis
C1 deficiency
inefficney clearing of antigen antibody complex
CGD
NADPH defect
CHS
lysosomal trafficking disorder
Low H or I =
low C3
Has an aa that makes direct contact with the epitope
Hypervariable region
BCR requires membrane bound antibody and. . .
Association of IgB and IgA
Does not have a switch region
IgD
To get a diff Antibody class, you must
Cut the DNA
B cell make an RNA t script that has
Mu and Delta
DNA splicing gives you
VDJ diversity
Mature B cel must have
LC, HC and IgM
We cut/splice D and J to bring in a V which gives IgM . This occurs in
Pro stage
Marker to identify the B precursor is ready to go through developmental stages
CD-19
For pro B to become pre B , the . . .
HC has to be able to pair with surrogate LC (V-pre B and lambda 5)
“Functional B cell”
good structure
good surrogate
can interact with signaling molecules
Allelic exclusion takes place in the
Pre-B cell stage
As long as the LC segments have 1., they can keep splicing .
V and D
What is central tolerance
deletion of auto reactive B cells in BM
Follicular B cells give
high aff AB that is a class other than IgM
B-1 gives
low aff , but rapidly active IgM
MZ B cells
move to marginal zone of spleen. TO produce low aff AB and can differentiate into plasma cells.
Transitional B cells
Express IgD
RAG mutation
Wont go from pro to pre. cant make proteins , because it cant make a HC
Results in SCIDs due to inability of B and T to pass developmental checkpoints.
Gamma common chain mutation
low T and low B
Associated with SCF and IL-7 which signal by gamma
XLA
Mutation in BTK. Producing mutated BTK enzyme.
Impairs pre- BCR signaling.
No B cells and low or absent immunoglobulin
BTK is necessary to to signal from
IgA and IgB
Associated with B cell activation
CR2, CD19, CD81
Cross links several BCRs , can also bind PRR (like TLRs) plus a BCR antigen . Antigen specificity is low
TI ( low aff IgM is produced )
Requires MHCII, high aff IgM. Antigen has to be a protein
TD
TI-1
cross link BCR, but also binds to TLR (low aff IgM)
TI-2
cross linking multiple BCRs, produces activation , extensive cross linking.
TD-B cell activation leads to
germinal center formation
TD-B cell activation steps
- SHM
- Aff maturation
- Isotype switching
SHM, mutation occurs in
VDJ of LC , point mutations
Aff maturation in TD-B cell development requires
Follicular dendritic cells (fly traps)
These can bypass germinal center and make IgG
TLRs
Classs switching requires
- Switch regions
- Enzyme (Activation induces cytidine deaminase) aka, ,,AID-causes looping of DNA .. only ssDNA regions that are undergoing transcription
CD40-L deficiency
hyper IgM syndrome -increase infection .. also patients will have lots of macrophage activation
These Ig have J chains
IgM and IgA
Poly Ig receptor
binds to J chains and moves IgA
Placental
IgG
Agglutinating
IgM>IgA