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Immunophysiology
for PHGY 313
48
Physiology
Undergraduate 3
08/22/2012

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Term
TLR
Definition
Toll Like Receptor
PRR
Uses signalling pathway
TIR (Toll IL1 Receptor) for intracellular signalling
Term
TLR Classes
1,2,3,4,5,7,9
Definition
Gram negative LPS
TLR 1:TLR 2
TLR 4
TLR 2:6

Flagellin: TLR 5

CPG Repeats: TLR 9

ssRNA: TLR 7
dsRNA: TLR 3
Term
LPS Recognition By TLR 4
Definition
LBP binds LPS and presents to CD14 on cell surface which conjugates with membrane of APC and TLR 4
Signal is ingested and broken down into CPG repeats and presented on TLR 9 for signal amplification

APC Travels to paracortex of regional lymph to present to lymphocytes with costimulatory molecules and cytokines
Term
IL
(1,4,6,8)
Definition
IL-1 - Enhances lymphocyte function
IL-2 - Promotes CD8 Proliferation
IL-4 - Induces IgE, Ihibits Th1
IL-6 - Promotes Th17, Inhibits Treg
IL-8 - Chemoattractant for Neutrophils and Macrophages, promotes cell adhesion
IL-12- Activates Th1, released by dendritic cells
Term
TNF-a
Definition
Leakiness of vascular epithelium
Term
Dendritic Cells
Definition
Most immunogenic APC
Bridge between innate and adaptive IS
Term
TLR Signalling
Definition
TIR-MyD88
IRAK-TRAF6
....
NF-kB which is translocated to nucleus to upregulate cytokines, costim molecules, phagocytosis, and MHCs
Term
CD8+
Definition
CTL (Cytoxic T Lymphocytes)
Recognize cells with intracellular virus or bacteria infection
Binds MHC I at a1,a2 junction
2 Ig-like domains
a B heterodimer
Use cytotoxic granules - perforin and granzyme
Term
CD4+
Definition
Helper T cells
Th1 - intracellular w/ B Cell
Th2 - Extracellular w/ NK, Macrophage, CTL
Th17 - Enhance neutrophil response - found in gut
Th1, 2, 17 promote inflammation - effector T cells
Treg - suppresses T cells

4 Ig like domains (D1-4)
Binds to MHC II (D1-B2)
Term
Antibodies (IgG strategies in different compartments)
Definition
Deal with extracellular pathogens
Via complement (plasma) - lysis and phagocytosis
Via opsonization (extracellular) - phagocytosis by macrophage
Recognize whole antigen
Via neutralization (toxin) - ingestion
Term
Antibody by location
Definition
IgG - extracellular, plasma
IgM - plasma (pentamer)
IgA - extracellular, (dimer) mucosa sites (gut)
IgE - mast cells at mucosa
Term
IgM
Definition
Predominant in early life
Activates complement
Pentamer
Term
IgG
Definition
Opsonization, complement and Neutralization
Term
IgA
Definition
Neutralization
Term
IgE
Definition
Mast cell sensitization
Term
Thymus-Dependent (TD) B Cell activation
Definition
B cells take up antigen present to Th cell in thymus
Co stim by CD40 (on B cell) and CD40L interaction (T cell)
and cytokine (if missing one....anergy)
Term
Thymus-independent (Ti) B Cell activation
Definition
TIA Type 1 - TLR agonists
TIA type 2 - Many ags activate antibodies on B cell
Term
Class switching
Definition
Antibodies change from one Ig to another
CD40 ligand on T cell, cytokines to direct
Term
Th1
Definition
Intracellular pathogens
Makes IFN-y
B cell activation CD40-CD40L
Class switching (Especially to to IgE)
Term
IFN-y
Definition

Inhibits IgE

Inhibits Th2, Th17

Upregulated by Th1 - B Cell conjugation

Term
TGF-B
Definition
Activates IgA
Promotes Th17, Treg
Term
4By
AE
Definition
IL-4 - IgE (+)
TGF-B - IgA (+)
IFN-y - IgE (-)
Term
Th2
Definition
For cell mediated killing - NK Macrophage CD8+CTL
Term
Cell-mediated immunity
Definition
NK cell or C8+ CTL or Macrophage
Co stimulation by Th2 cells
Recognize antigen epitopes on MHC
Term
Ig Structure
Definition
2 Heavy chains
2 light chains (k or lambda)
Disulfide bonds on hinge region
Variable region
Constant Region
2 Fab portions - fragment for antigen binding
Term
RSS
Definition
Recombination signal sequence
DNA sequence on ends of V J and D sequences for recombination
Term
Order of factors in VDJ recombination (somatic recombination)
Definition
RAG-1, RAG-2 (Recombination Activating Genes) - brings RSS together
Ku70, Ku80 - DNA Binding Protein (hairpin binding)
Artemis - nuclease open hair pin
DNA-PK - open hairpin
TdT - Adds diversity Terminal deoxynucleotide transferase
DNA ligase IV (XRCC4) - LIgates ends to finish region
Term
Central tolerance
Definition
Testing in bone marrow to ensure antibodies do not bind to strongly or too weakly to antigens. ensures against autoimmunity.
Positive and negative selection
Term
Peripheral tolerance
Definition
Inactivation of mature lymphocytes by secondary lymphoid organ
Term
CLP
Definition
Common Lymphoid Progenitor - B and T cell precursor
Term
Anaphlotoxins
Definition
Chemoattractants in extracellular space that promote inflammation
C5a is the strongest
Term
T cell receptor - TCR (binding and signalling)
Definition
Looks like Fab
aB or yd
coupled to CD3
RAG proteins ensure aB or yd only
Binds to non-self MHC and Self-MHC with a non-self antigen
Term
CD3
Definition
intracellular signalling portion of TCR-CD3 complex
5 invariant polypeptide chains yedzn in heterodimers ye de zz
Signal transduction via ITAM immunoreceptor tyrosine activations motif
Term
Antigen recognition
Definition
B Cell full extracellular antigen via antibody
T Cell partial via MHC
Term
MHC I
Definition
Present on all nucleated cells
peptide fragment
made of a1:B2microglobulin and a2:a3 subunits
Binding cleft is made of a1:a2
Exhibits endogenous/intracellular antigens to CD8+ T cell
Term
MHC II Presentation
Definition
MHC a1 and B1 make up the binding cleft with a2 and B2 subunits attached. Invariant chain attaches to binding cleft. MHC buds off via the golgi and the pH cause the invariant chain to break off leaving only CLIP in the binding cleft. A phagolysosome containing antigen phagocytosed from the environment fuses with the vesicle containing MHC II. HLA-DM dissociates CLIP and presents antigen to MHC II. MHC II vesicle is then fused with the membrane for recognition by CD4+ T cell
Term
MHC I Presentation
Definition
MHC a1 is bound to B2m with association to calnexin.
Along with the non-covalently bound a2 and a3 chains calrectin, along with ERP 57 induces a change in the structure to keep the binding cleft open. Tapasin associates to the MHC along with TAP (tapasin associated antigen presenter. TAP takes an antigen which has been cleaved by the proteosome and presents it to MHC I by bringing it into the ER. MHC is then attached to the membrane for association by CD8+ T cells
Term
MHC II
Definition
Present on APCs
a1b1 make up antigen binding cleft
a2b2 bound non-covalently
exhibits extracellular antigens phagocytosed by cell
Binds CD4+ T Cell
Term
Thymus testing
Definition
Cortical - Positive
Medullary - Negative
Protects against too strong or too weak binding
Term
yd T cell
Definition
DN T cells
Bind whole antigens
Resident in gut
More common during gestation
Determined at DN2 Stage
Term
aB Thymocyte proliferation (Checkpoint, determination, stages, factors)
Definition
More common after birth
c-kit and CD-44 through 1,2 CD-25 through 2,3
Go through DN2,3,4 Stages then DP stage then determination
RAG are turned on in late DN2-DN3 stage
B gets rearranged first
need to express B and pre-T a receptor to become DP
Tested for tolerance then determined to CD4+ vs CD8+
Term
c-kit
Definition
Stem cell growth factor
In T cell determination
Term
CD-44
Definition
adhesion molecule
In T cell determination
Term
CD-25
Definition
IL-2 Receptor a chain
In T cell determination
Term
AIRE
Definition
Transcription factor which expresses all peptides in genome for autoimmunity testing
Term
APC - T Cell signalling
Definition
1. Activation - MHC II-antigen-TCR binding
2. Survival - Co stimulation (upregulated by PRR PAMPS)- B7.1/B7.2-CD28 Binding
3. Differentiation - Cytokine - IL-6 IL-12 TGF-B
Term
Perforin
Definition
Exocytosed by CD8+ T cell
Polymerize to form pore on cell
Allows granzyme to enter and cause apoptosis
Term
Granzyme
Definition
Passed through perforin pore to induce apoptosis by CD8+ CTL
Chromatin and nucleus condensation then Phosphatidylserine residues flipped to outside to allow recognition by phagocyte
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