Term
| A cell interprets its surroundings through _____ |
|
Definition
the binding of
signalingmolecules to cell-associated receptors |
|
|
Term
| Binding of a ligand to its receptor by what kind of bonds? |
|
Definition
non-covalent...mostly
covalent are the least likely |
|
|
Term
Binding leads to changes in the receptor’s conformation...
that allows it to tranduce the ligand-binding signal to the_______ |
|
Definition
|
|
Term
|
Definition
what instructs a cell to change
its metabolic or proliferative state |
|
|
Term
|
Definition
| ligands that faciliate communication between different immune cells. |
|
|
Term
|
Definition
| special cytokines that induce chemoattraction or repulsion. |
|
|
Term
|
Definition
a molecular change in the receptor that leads to a
signal. It may take more than one ligand binding to receptors to get a signal. |
|
|
Term
The low affinity ____ is a heterodimer. It binds only
at high concentrations. The ____ a heterotrimer, which is a high affinity form that binds
Some biological receptors are multivalent, meaning they have more thanone ligand binding site.
A B cell receptor binds two, identical antigens at once, which
increases the strength of binding between a B cell and its target. |
|
Definition
|
|
Term
| Binding of receptor by ligand induces clustering of receptors and signaling molecules into _____ |
|
Definition
|
|
Term
Activation of receptor –associated _____ is often
observed. |
|
Definition
|
|
Term
| after activation of the tyrosine kinase receptor.. on the membrane... |
|
Definition
| adaptor molecules bind to the receptor beneath the membrane onto receptor associated molecules and the tyrosine kinase associated receptor making a scaffold for things to come. |
|
|
Term
| ___________ are transcription factors that modulate gene expression |
|
Definition
|
|
Term
the receptor interact with and activate a variety of
down stream enzymes: |
|
Definition
PLC, PI3 kinase, and additional
kinases. At this point the signal is being transduced |
|
|
Term
Activation of PLC leads to cleavage of phosphatidyl inositol
bisphosphate and generation of ______ |
|
Definition
|
|
Term
|
Definition
second messenger that causes release of
calcium ions
from the endoplasmic reticulum. |
|
|
Term
Calcium flux then leads to activation of calcineurin. Calcineurin is a
phosphatase that _______ |
|
Definition
dephosphorylates and activates the
transcription factor NFAT |
|
|
Term
Diacylglycerol remains at the membrane and helps to
activate protein kinase C,
which then leads to _______ |
|
Definition
| activation of the transcription factor, NF-kB. |
|
|
Term
Ras-GRP/Sos bind to the signaling complex. This leads to
activation of the Ras/Map Kinase pathway and activation of ____ |
|
Definition
| the AP-1 transcription factor. |
|
|
Term
| Induction of Conformational Changes or (aka) __________ |
|
Definition
| Dimerization of Receptors |
|
|
Term
| Some growth factors that regulate immune responses induce dimerization of _______. |
|
Definition
|
|
Term
| Dimerization is followed by reciprocal _____________ |
|
Definition
| tyrosine phosphorylation of the receptor molecules. |
|
|
Term
| Stem cell factor binds to the c-kit receptor on the surface of bone marrow _______ |
|
Definition
|
|
Term
| BCR and TCR Require Receptor-Associated Molecules to Signal Cell ______ |
|
Definition
|
|
Term
B cell and T cell receptors have very short cytoplasmic tails
and therefore require ______ |
|
Definition
receptor-associated molecules
and co-receptors for signal transduction. |
|
|
Term
| The B cell receptor requires _______ to transmit signals. |
|
Definition
| Ig alpha / Ig beta heterodimer |
|
|
Term
| Besides Ig alpha and Ig beta heterodimers , the B cell receptor requires __________ |
|
Definition
interaction
with CD19, CD21, CD81, and C3d |
|
|
Term
| The cytoplasmic region of the receptor-immunoreceptor contain _____________ |
|
Definition
| tyrosine activation motifs (ITAMs) |
|
|
Term
| Phosphorylation of ITAMs allows _____ |
|
Definition
for binding of downstream adaptor
molecules and signal transduction
(shape shifting to go into the cell) |
|
|
Term
| The T cell receptor requires the __________ to transmit signals. |
|
Definition
CD3 complex, CD4 or CD8, and CD28
for the T cell receptor..
((compare with B cell Ig alpha/Ig beta
CD19, CD21, CD81, and C3d ))) |
|
|
Term
The T cell receptor TCR recognizes ______
then compare with B cell receptor BCR |
|
Definition
antigen in the context of MHC molecules located on the antigen presenting cell.
But BCR is a heterodimer called Ig-α/Ig-β (CD79), bound together by disulfide bridges. |
|
|
Term
In the T cell, ___ help to
facilitate interaction with the MHC molecules. |
|
Definition
|
|
Term
In the T cell, _____transduces signal once the TCR recognizes the
antigen. |
|
Definition
|
|
Term
| In the T cell, ___ recognizes additional molecules on the antigen presenting cell and acts as a costimulatory molecules |
|
Definition
|
|
Term
| Both B and T cell receptor need __________for signal transduction. |
|
Definition
| receptor associated molecules and co-receptors |
|
|
Term
| T cell receptors use ____ and a pair of zeta chains....CE4 and CD8 receptors bind to the non poluymorphic region of the MHC 2 and 1 respectively |
|
Definition
| CD3 which is a complex of delta epsilon / gamma epsilon) |
|
|
Term
| B cell receptors use _____to transmit their signal.. |
|
Definition
|
|
Term
|
Definition
Ligand-induced clustering of B/T cell receptors slows down the rates of receptor diffusion in the membrane and
facilitates movement of the B/T cell membrane making it easier to put in the lipid raft.. |
|
|
Term
|
Definition
| Lipid rafts are highly ordered, detergent insoluble, cholesterol and sphingolipid-rich membrane regions. Are populated by molecules that are critical to receptor signaling |
|
|
Term
B cell rafts...
If the B cell is resting the receptor is not in the raft.. |
|
Definition
B cell rafts have tyrosine kinases such as Lyn. B cell receptor binds to antigen, the B cell receptor clusters moving to the
lipid rafts . Moving to the raft allows the B cell receptor to make contact with Lyn. Lyn activates and then phosphorylates
receptor associated proteins Iga/Igb. Their activation leads to a signaling cascade |
|
|
Term
| T cell Receptor Specific Signaling _____ |
|
Definition
|
|
Term
| Many of the tyrosine kinases that initiate BCR and TCR activation belong to a family of enzymes known as |
|
Definition
| SRC - family kinases "sark" ..(that was first identified in bird fibrosarcoma proving it imp in regulating).. |
|
|
Term
| Numerous signaling molecules are called _____ |
|
Definition
| ligands ligands are usually antigen or foreign particlesin immunology..at least in this chapter. |
|
|
Term
| what are some antigen presenting cells that are beautiful to T cells and will activate a handsome T cell? |
|
Definition
| dendritic cells and macrophages and B cells PROFESSIONALS, present antigen to the handsome T cell.. ESPECIALLY dendritics are for naive T cells |
|
|
Term
T cell Receptor Specific Signaling—Pathway Number 1
. |
|
Definition
TCR engagement by antigen/MHC complexes leads to
NFAT activation |
|
|
Term
| binding of receptor to ligand makes the receptors and signaling molecules _______ |
|
Definition
|
|
Term
binding of ligand may happen along with binding of ____ to their own ligands..causing activation of receptor associated tyrosine kinases..
tyrosine kinases that phosphorylate receptor-associated proteins.. |
|
Definition
|
|
Term
| after the ligand activates the receptor and associated co-receptors the next binding is of |
|
Definition
| adaptors that create a scaffolding at the membrane..which enable various enzyme activations. which go on to cause the release of calcium ions. |
|
|
Term
| receptors on the ____ cause the release of calcium ions |
|
Definition
|
|
Term
| the release of calcium ions then activate calcineurin which dephosphorylates ____ |
|
Definition
| the transcription factor NFAT , allowing it to enter the nucleus. |
|
|
Term
| In B cells, what keeps the antigen in contact with the receptor? |
|
Definition
| Interaction between CD 3 on the antigen and ..Cd 21 . |
|
|
Term
| What allows binding allows downstream binding of adaptors and helps transduction from the receptors? |
|
Definition
| ITAMs = immune receptor tyrosine Motifs |
|
|
Term
| B cells have what kind of antibodies |
|
Definition
|
|
Term
| in B cells what initiates the cascade of phosphorylation of Ig alpha and Ig beta |
|
Definition
|
|
Term
This movement allows the B cell receptor to make contact with Lyn. Lyn activates and then phosphorylates
receptor associated proteins Iga/Igb. Their activation leads to a signaling cascade. |
|
Definition
| movement into rafts. Rafts in B cells are populated with tyrosine kinases such as Lyn. |
|
|
Term
|
Definition
1. primary transcript
2. secreted 3. membrane-bound
2 and 3 are processed transcripts
4 hydrophilic segment (inner)
5. membrane bound segments |
|
|
Term
| two groups of light chains on B antibodies are |
|
Definition
|
|
Term
The 5 antibody classes
(the heavy chain determines its class) |
|
Definition
IgM IgD IgA IgG IgE
mu delta alpha gamma epsilon |
|
|
Term
|
Definition
| 2 heavy chains and 2 light chains |
|
|
Term
| immunoglobulin or antibodies are proteins that have 4 kinds of structures |
|
Definition
| primary, secondary, tertiary, and quaternary structure |
|
|
Term
| Light chain have 2 domains |
|
Definition
1 variable and 1 constant
V L C L |
|
|
Term
| Heavy chains have domains |
|
Definition
1 variable (V H ) and three or four constant domains C H 1 - C H 4
HEAVY CHAINS DETERMINE ANTIBODY FUNCTION |
|
|
Term
| One thing that increases a B cells binding strength? |
|
Definition
| It binds 2 identical antigens at once = mulitvalent |
|
|
Term
| some bonding types in receptors for ligands |
|
Definition
| hydrogen bond, ionic bond, hydrophobic interactions, van der Waals interactions |
|
|
Term
| the antigen binding site is _____to the epitope to which it binds |
|
Definition
complementary
hypervariable regions = complementary-determining-regions ( C D R) |
|
|
Term
| 3 V H and 3 V L chain CDRs are located |
|
Definition
| on the lloops tht connect the betas strands of the V H and V L domains. amino acids of CDRs vary in length and sequence. |
|
|
Term
| Stem cell factors bind to the ___ on the surface of bone marrow stromal cells. |
|
Definition
|
|
Term
| some growth factors that regulate immune responses induce dimerization of their receptors. Dimerization is followed by ____ |
|
Definition
| reciprocal tyrosine phosphorylation of the receptor molecule |
|
|
Term
| B cell receptors require ____ to transmit signals. and some other interactins with ___ |
|
Definition
Ig alpha / Ig beta heterodimer
CD 19, CD 21, Cd 81 and C3D |
|
|
Term
| The cytoplasmic region of the receptor associated molecules contain ________ . Phosphorylation of _____allows for binding of downstream adaptor molecules and signal transduction. |
|
Definition
| ITAMs immune receptor tyrosine activation motifs |
|
|
Term
Antibodies
Two major functions: |
|
Definition
Binding foreign antigens encountered by the host.
2. Mediating effector functions to neutralize or eliminate
foreign invaders |
|
|
Term
The ___ class of antibodies which are the most abundant class of antibodies are found in the alpha and beta -globulin
fraction of serum. Some -globulin as well as other antibody classes are found in the and globulin
fractions |
|
Definition
|
|
Term
All ___six of an antigen binding site make contact with the antigen for which they are specific.
VH domains often contribute more to antigen binding than do VL domains. |
|
Definition
|
|
Term
| name the players in T cell specific signaling path 1 that activates NFAT to modulate gene expression..including the cytokine IL-2..important in regulating T cell |
|
Definition
| TCR / CD3, ITK, LCK , LAT at the membrane. Lat binds to CD3 and signals PLC...PLC cleaves PIP2 making DAG and IP3.. goes to ER for Ca++ release .. CA++ with calcineurin activate calmodulin which activate NFAT |
|
|
Term
| TCR signaling pathway 2 that activates AP-1 to up regulate IL-2 ..main players: |
|
Definition
| Ras is a GTPase ..guanine exchange factor GEFs and GTPase activate GAPS. Ras starts after TCR binds MCH antigen. DAG is released by PLC cleavage of PIP2. DAG activates ras-GRP/SOS..SOS is a GEF for Ras. Ras let go of GDP and binds to GTP, activating Ras. Ras binds Raf (serine/threonine kinase) the first of MAP kinase cascade. Raf actiates MEK, ERK is a MAP kinase. ERK activate Elk 1 that goes in nucleus and combines with serum response factor SRF to activate the fos gene that combines with Jun to generate AP-2 transcription factor complex that up regulate expression of IL-2 |
|
|
Term
| T cell Receptor specific signaling path way 3... for NFkB for expression of the IL-2 gene |
|
Definition
DAG generated by PLC-mediated cleavage of PIP2 helps to
activate protein kinase C (PKC), another serine/threonine
kinase. PKC activate the adaptor protein Carma-1 starting the cascade to recruit ubiniquitin ligase, TRAF6. PKC actives the kinase TAK 1. TRAF6 and TAK1 regulate the IKK comples. TRAF6 ubiquitinates IKK..TAK1 phosphorylates the complex to activate IKK. IKK activates IkB.. that is complexed to NFkB which modulate gene expression... IL-2 genes is one |
|
|
Term
Antibody structure: Each light chain is bound to a heavy chain by one interchain ____and by____ interactions such as salt linkages,
hydrogen bonds, and ____interactions.
Similar bonds including two disulfide bonds link the heavy/light
chain heterodimer to a second heavy/light chain to form ____
a four chain antibody structure.
Many intrachain disulfide linkages contribute to the tertiary
structure of each heavy and light chain. |
|
Definition
disulfide bond
noncovalent
hydrophobic
heterodimer |
|
|
Term
Many intrachain _____contribute to the tertiary
structure of each heavy and light chain. |
|
Definition
|
|
Term
V regions:
Made from the first 110 amino acids of the amino terminal region of a light or heavy chain. Highly variable.
Varies greatly among antibodies of different __________ |
|
Definition
antigen specificity.
VL and VH |
|
|
Term
Complementarity Determining Regions
Areas of the VL and VH that constitute the _______________. |
|
Definition
|
|
Term
_______are regions of the antibody molecule that are beyond the V regions.
Regions of relatively constant sequence. CL and CH |
|
Definition
|
|
Term
Two Types of Light Chains
Light chain are highly variable in
sequence = ______
The carboxy terminal amino acid sequence of light chains are not as variable in sequence = _____Two groups of light chains were determined
based on the constant region sequences.
Kappa (k) Lambda (l)
In humans, 60% of the light chains are kappa |
|
Definition
variable region
constant region. |
|
|
Term
Five Antibody Classes
The amino terminal end of the heavy chain protein is highly
variable and forms a ____The remainder of the heavy chain protein is constant (C).Five basic heavy-chain constant regions (isotypes) have been identified: μ, d, alpha, gamma, epsilon (IgM,IgD,IgA,IgE )
The heavy chain |
|
Definition
variable regions
(VH). the tips are variable..and I think..the variable light tips bind the antigen... and I think that's the Fab region |
|
|
Term
The ______of an antibody
determines its class...A single antibody molecule has two
identical heavy chains and two identical light chains. |
|
Definition
|
|
Term
| Immunoglobulin fold domains are generated when a polypeptide folds into a series of anti-parallel ______ |
|
Definition
|
|
Term
Beta strands are stabilized by _____
between the amino groups in one strand and
carbonyl groups of an adjacent strand |
|
Definition
|
|
Term
Beta sheets of alternating _____amino acids whose side chains are
arranged perpendicular to the plane of the sheet.
Hydrophobic amino acids are oriented toward the interior of the sandwich and hydrophilic amino acids
are face outward.
Beta sheets within an immunoglobulin fold are stabilized by hydrophobic interactions and by a disulfide bond.
V domains and C domains are similar in structure. |
|
Definition
hydrophobic and
hydrophilic |
|
|
Term
Ig fold promotes ______identical domains (CH2/CH2) and non-identical domains
(VH/VL). |
|
Definition
|
|
Term
The antigen binding function of an antibody is accomplished by the ____. VL and VH domains from one antibody to the next exhibit a great deal of sequence variation, which allows for recognition of unique and different
antigens |
|
Definition
|
|
Term
_____ = regions with the greatest
variability that form the antigen binding site.
The antigen binding site is complementary to the __ which it binds. |
|
Definition
Hypervariable regions
epitope |
|
|
Term
| Hypervariable regions = ______CDRs) because they are complementary to the epitope of the antigen. |
|
Definition
complementarity determining
regions |
|
|
Term
| 3 VH and 3 VL chain CDRs are located on _____ the beta strands of the VH and VL domains. Amino acids of CDRs vary in length and sequence. |
|
Definition
|
|
Term
| _____ are areas outside of the CDRs that exhibit less variation |
|
Definition
|
|
Term
All six CDRs of an ___ make contact with the antigen for which they are specific.
VH domains often contribute more to antigen binding than do VL domains. |
|
Definition
|
|
Term
The immunoglobulin fold domain is found in other proteins besides the immunoglobulin.
The structural properties of an immunoglobulin fold explain why it has been used in so many proteins with ____ . immunoglobulin domains
facilitate recognition or adhesion. |
|
Definition
| recognition or adhesive function |
|
|
Term
In the Mononuclear Phagocytic System
____ are the progenitor that gives rise to monocytes and macrophages. |
|
Definition
| CMPs common myeloid progenitor |
|
|
Term
__ gives rise to B, T, and NK cells.
___ gives rise to all red blood cells,
granulocytes, monocytes, and macrophages. |
|
Definition
CLP common lymphoid progenitors
CMP common myeloid progenitor |
|
|
Term
| Regions of TCR and BCR that are variable in their AA sequences are known for |
|
Definition
|
|
Term
The S-S bond between the constant region domains in antigen
helps to ____________ |
|
Definition
| hold the VH and VL domains together. |
|
|
Term
Hinge regions in antibodies are flexible due in part to the prominence of proline residues.
The antigen binding arms can assume a variety of angles, which facilitates ____.
The hinge region also contains a variable number of cysteines which form interchain,
disulfide linkages that hold the chains together. |
|
Definition
|
|
Term
Hinge regions in antibodies are flexible due in part to the prominence of prolineresidues.
The antigen binding arms can assume a variety of angles, which facilitates ___.
The hinge region also contains a variable number of cysteines which form interchain,
disulfide linkages that hold the chains together.
The subclasses of IgG shown below exhibit a great variability in the number of these
disulfide linkages. |
|
Definition
|
|
Term
The CH2 domains of alpha, delta and
gamma chains and the CH3 domains of
mu and episilon heavy chains are
separated from their partner heavy
chains by ______ |
|
Definition
carbohydrate (CHO) side
chains = prevents the two
heavy chains for nestling too closely
together. |
|
|
Term
The B cell’s antibody will always recognize the same antigen, but the antibody may be _______
because of differential splicing and polyadenylation of its heavy
chain transcript. |
|
Definition
|
|
Term
B cell signaling...BCR includes the
membrane bound form of the B cell’s antibody
(Heavy and Light chains) in association with the
together with . |
|
Definition
| Ig alpha /Ig beta heterodimer |
|
|
Term
Antigen binding promotes______ with Ig alpha /Ig beta heterodimer, src kinases,
coreceptors CD19/CD21, adaptor proteins (BLNK and BCAP). |
|
Definition
| clustering of the receptor |
|
|
Term
BCAP & CD19 recruit PI3 kinase to the
membrane to generate PIP2. This serves as a docking site for AKT and PDK1, which initiate the anti-apoptotic signaling cascade which leads to __________ |
|
Definition
|
|
Term
BRC. The src kinase __ phosphorylates, Ig/Ig
heterodimer, providing docking sites for BLNK.
BLNK recruites PLC and BTK. |
|
Definition
| lyn... lyn is specific to B cells |
|
|
Term
BCR (cont.) PLC cleaves PIP2, ultimately generating DAG
and IP3. ____ releases calcium stores from the ER. |
|
Definition
|
|
Term
This leads to activation of calmodulin/calcineurin,
which _____ and activates the NFAT
transcription factor. |
|
Definition
|
|
Term
Release of calcium and generation of DAG also
leads to _____ which promotes
activation of the NFkB transcription factor. . |
|
Definition
|
|
Term
BCR (cont) BLNK recruites
the Grb2/Sos complex which acts
as a GEF for the G protein Ras. Activated ras then turns on the Map kinase cascade and _____________ |
|
Definition
| activation of the AP-1 transcription factor. |
|
|
Term
| Name the three transcription factors that work in concert to modulate the expression of genes that regulate B cell proliferation and maturation. |
|
Definition
they are the same factor that are used in T cell regulation:
NFAT NFkappaB AP-1 |
|
|
Term
T Cell Receptor..The T cell receptor (TCR) is a heterodimer made up of either alpha/ beta or gamma /delta proteins. The TCR is expressed in association with the __complex which is made of
gamma/ epsilon homodimers, / heterodimers,
and / heterodimers. The CD3 complex provides the signaling function. Immunoreceptor
Tyrosine Activation Motifs (ITAMS) are found in several of the CD3 family members and serve as
docking sites for adaptor proteins |
|
Definition
|
|
Term
The TCR as well as several of the ___proteins are members of the Immunoglobulin superfamily
because they have immunoglobulin domains |
|
Definition
|
|
Term
The amino terminal end of the TCR proteins is the ___, antigen binding end. The COOH end
is the constant end. The transmembrane region has some strategically placed, positively charged
amino acids which promote interaction of the TCR with CD3 members. |
|
Definition
|
|
Term
The alpha/beta and the gamma/delta forms of the T cell receptor differ structurally in terms of their
________.
The majority of circulating T cells are the alpha /beta form, which recognize antigen in the
context of MHC.
A small subset of T cells is the / form which can recognize antigens that are presented by MHC molecules or non MHC molecules. Some / T cells do not require antigen to be presented at all. |
|
Definition
|
|
Term
The TCR associates with other molecules besides the CD3 complex. This includes molecules such
as _____. Many of these accessory molecules are also members of the Ig superfamily. |
|
Definition
CD4 and CD8 CD4 on helper T Cells
and CD8 on cytotoxic T cells |
|
|
Term
For a naïve T cell
to become activated, it has to be simultaneously signaled through the _____. |
|
Definition
|
|
Term
| CD4 and CD8 are important _____for the T cell. |
|
Definition
|
|
Term
| CD4 is a ___ while CD8 is a heterodimer |
|
Definition
|
|
Term
| CD4 is expressed on helper T cells and help these cells recognize ________ molecules. |
|
Definition
|
|
Term
CD8 is expressed on cytotoxic T cells and
help these cells recognize _______ |
|
Definition
|
|
Term
The co-engagement of a single MHC molecule by
both the TCR and its CD4 or CD8 co-receptor
enhances the ____ of T cell binding to its target |
|
Definition
|
|
Term
Interleukin 2 (IL-2) is a type of ________. It is a protein that regulates ,,produced by activated T cells during an immune response stimulates itself
( autocrine-paracrine ) and NKCs |
|
Definition
| cytokine signaling molecule |
|
|
Term
|
Definition
|
|
Term
| T cells need a third molecule to increase affinity tri-molecular affinity |
|
Definition
| MHC co stimulator T4 or T8 and I don't know, maybe CD4 or L2? |
|
|
Term
| _____________ is the recognition component of the B cell antigen receptor (BCR), |
|
Definition
|
|
Term
| ___ affects lymphocyte activation, cytokine production, and elaboration of cell-surface molecules. |
|
Definition
|
|
Term
| signaling pathways are initiated by TCRs binding to peptide _____. |
|
Definition
|
|
Term
| The function of T-lymphocytes during adaptive immune responses is directed by ___________________ |
|
Definition
| antigen receptors, costimulatory molecules, and cytokines |
|
|
Term
serine/threonine kinases that are controlled by lipid second messengers such as polyunsaturated diacylglycerols (DAG) and phosphatidylinositol -trisphosphate (PIP3),
are important parts of __________ |
|
Definition
| T-cell signal transduction. |
|
|
Term
The MAP kinases are activated by a kinase cascade involving
a MAP kinase kinase (MKK) that phosphorylates and stimulates the ____ and 2 kinases directly |
|
Definition
|
|
