Feb. 2004
‫טבלת מושגים באימונולוגיה‬
-‫הגדרות עפ"י הספר‬
Immunobiology 5th addition
Charles A Janeway
.‫ מציין מושגים שהופיעו בשקפים אך לא נראה לי שהוזכרו בכיתה‬- ☺
.‫ייתכן מאד שיש מושגים שלא סימנתי בסמיילי ובכל אופן הם לא הוזכרו בשיעורים‬
.‫הטבלה אינה כוללת את כל המושגים שהוזכרו בשיעורים‬
NAME
4-IBB, 4-IBBL ☺
AP-1
☺
Apaf-1
B7.1, B7.2
Bcl-2
Blk
C3b
Calnexin
☺
Calreticulin
☺
CAMs
CD131
☺
CD132
☺
Definition
Activated APC express 4-IBBL which co-stimulates naïve CD8 T
cells (T cell expresses the 4-IBB).
A family of transcription factors which are hetrodimers of the Fos
and Jun proteins. Are phosphorylated and activated by the MAP
kinase cascade. See also NFAT.
See Bcl-2.
See CD80, CD86.
A death inhibiting protein. During apoptosis the mytochondria
swell, allowing cytochrome c to leak out of the mytochondria into
the cytosol. In the cytosol, cytochrome c interacts with APAF-1,
forming with it a complex that can activate caspases. An activated
caspase cleaves I-CAD, which leads to DNA fragmentation. Bcl2 interacts with the mitochondrial outer membrane and blocks
mitochondrial swelling that leads the cytochrome c release. Also
see I-CAD.
See Fyn
Complement component that binds to immune complexes
(antibody:antigen complexes). Bound C3b binds to the receptor
CR1 on erythrocyte surfaces. These erythrocytes are transported
to the liver and spleen where macrophages bearing CR1 and Fc
receptors remove the complexes from the erythrocyte surface
without destroying the cell, and then degrade them.
A protein found in the ER. It binds to partly folded members of
the Ig-superfamily of proteins (in our case- MHC class I α chain)
and retains them in the ER until folding is completed.
A molecular chaperon that binds to MHC class I and to MHC
class II. (was mentioned in the context of delivering peptides via
MHC to the cell surface).
Cell Adhesion Molecule. Lymphoid progenitor cells and pro-B
cells bind to them. Similar function as VCAM-1 (see VCAM-1).
Expressed on myeloid progenitors and granulocytes. Is the
common β subunit of IL-3, IL-5 and GM-CSF receptors.
Expressed on B cells, T cells, NK cells, mast cells and
neutrophils. Is the IL-2 receptor γ chain and is the common
1
CD14
CD19
CD2
☺
CD20
☺
CD21 (CR2)
CD22
CD24
CD25
☺
☺
☺
CD27
☺
CD28
CD3
CD30
☺
CD34
CD38
CD4
CD40
CD44
CD45-R
☺
subunit of IL-2, IL-4, IL-7, IL-9 and IL-15 receptors.
Receptor for complex of LPS and LPB. See LPS.
Expressed on B cells. Forms a complex with CD21 and CD81
which functions as a co-receptor for B cells. The cytoplasmic
domain binds cytoplasmic tyrosine kinases and PI3-kinase.
Expressed on T cells, thymocytes and NK cells. Functions as an
adhesion molecule, binding CD58 (LFA-3). Binds Lck
intracellularly and activates T cells.
Expressed on B cells. Oligomers of CD20 may form Ca2+
channel. Has a possible role in regulating B-cell activation.
Expressed on mature B cells and on follicular dentritic cells.
Functions as a receptor for the complement component C3d. with
CD19 and CD81, CD21 forms co-receptor for B cells.
Expressed on mature B cells.
Expressed on B cells and granulocytes.
Expressed on activated T cells, B cells and monocytes. IL-2
receptor.
Expressed on medullary thymocytes, T cells, NK cells and some
B cells. Binds CD70; can function as a co-stimulator for T and B
cells.
Expressed on T-cell subsets and activated B cells. Functions in
activating naïve T cells, as a receptor for co-stimulatory signals.
It binds CD80 and CD86.
Expressed on T cells. Is associated with the TCR. Required for
signal transduction by the TCR.
Expressed on activated T, B and NK cells, also expressed on
monocytes. Binds CD30L (CD153); cross linking CD30 enhances
proliferation of B and T cells.
Expressed on Hematopoietic precursors and on capillary
endothelium. It is the ligand for L-selectin.
Expressed on early B and T cells, activated T cells, germinal
center B cells and on plasma cells. It augments B cell
proliferation.
Expressed on TH1 and TH2 T cells, on monocytes and on
macrophages. Is a co-receptor for MHC class II molecules. Binds
Lck on cytoplasmatic face of membrane. Receptor for HIVs’
gp120.
Expressed on B cells, macrophages, dentritic cells and on basal
epithelial cells. It binds CD154 (CD40L). It functions as a
receptor for co-stimulatory signal for B cells, promotes growth,
differentiation and isotype switching of B cells. Also promotes
cytokine production by macrophages and dentritic cells.
Expressed on leukocytes and erythrocytes. Binds hyaluronic acid
and mediates adhesion of leukocytes.
The leukocyte common antigen, is a transmembrane tyrosine
2
CD5
☺
CD59 (protectin)
CD62L
CD69
☺
CD8
CD80
CD81 (TAPA-1)
CD86
CLIP
☺
CRP
CTLA-4 (CD152)
DAP12 and DAP10
DC-CK
☺
Eotaxin
Erp57
☺
☺
FADD
Fas
phosphatase found on all leukocytes. Naïve CD4 T cells express
the CD45-RA isoform, while effector and memory CD4 T cells
express the CD45-RO isoform. CD45 activates Lck and Fyn.
Expressed on Thymocytes, T cells and on a subset of B cells.
Binds complement components C8 and C9 and blocks assembly
of membrane-attack complex.
Expressed on B cells, T cells, monocytes and NK cells.
Functions as a Leukocyte Adhesion Molecule (LAM), binds
CD34. It also mediates rolling interactions with endothelium.
Expressed on activated T and B cells, activated macrophages and
NK cells.
Expressed on CTLs. Co-receptor for MHC class I molecules.
Binds Lck on cytoplasmatic face of membrane.
Expressed on B-cell subset . Functions in the co-stimulation of B
cells. Is the ligand for CD28 and CTLA-4.
Expressed on lymphocytes. Associates with CD19 and CD21 to
form B cell co-receptor.
Expressed on monocytes, activated B cells and dentritic cells.
Functions in the co-stimulation of B cells. Is the ligand for CD28
and CTLA-4
class II–associated invariant-chain peptide. Bound to the MHC
class II and doesn’t enable binding to peptides. HLA-DM binds to
MHC class II:CLIP complexes, catalyzing the release of CLIP
and the binding of antigenic peptides.
C-reactive protein. A protein secreted by the liver into the blood
as part of the acute-phase response, as a result of the action of IL1, IL-6 and TNF-α. It binds to the phosphorylcholine portion of
certain bacteria and fungal cell-wall lipopolysaccharid. When
CRP binds to a bacteria , it is not only able to opsonize it but can
also activate the complement..
Expressed on activated T cells. The receptor for CD80 and
CD86. Is a negative regulator of T cell activation.
Members of the ITAM-associated ζ-chain family that were
discovered on NK cells and have only one ITAM. They associate
with the KARs (see KAR)..
A chemokine that is expressed only in dentritic cells in lymphoid
tissues.
CC chemokine that acts specifically on eosinophils.
The same as calreticulin (not the exact same thing but a similar
chaperon).
The adaptor protein that interacts with the death domains in the
cytosolic tails of Fas.
A receptor on T cells that interacts with its ligand - Fas-L (a
member of TNFs). Both the receptor and the ligand are normally
induced during the course of an adaptive immune response. The
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FcγRIII (CD16)
FcεRI
FOS
Fyn
GEF
GlyCAM-1
GM-CSF
Granzymes
HCG
HLA
HLA-DM
I-CAD
ICAM-1
☺
FasL is a hetrodimer and when it binds it induces the
trimerization of Fas. This brings the death domains in the Fas
cytoplasmatic tails together. The signal transduced leads to
apoptosis. Fas ligand is secreted by activated TH1 cells and
enables them to kill chronically infected macrophages that lost
their ability to kill intracellular bacteria.
Expressed on Neutrophils, NK cells and macrophages. Is the
component of low affinity Fc receptor. It mediates phagocytosis
and antibody-dependent cell-mediated cytotoxity (ADCC).
A high affinity receptor on the surface of mast cells and basophils
which binds free IgE. When antigen binds this IgE and cross-links
the FcεRI, it causes mast-cell activation.
See AP-1, NFAT.
One of the receptor-associated Src-family tyrosine kinases, which
phosphorylate ITAMs upon receptor clustering.
Guanine nucleotide Exchange Factor. A protein that can remove
the bound GDP from small G proteins; this allows GTP to bind
and activate the G protein.
A molecule found on the high endothelial venules of lymphoid
tissues. It is an important ligand for the L-selectin molecule
expressed on naïve lymphocytes, directing these cells to leave the
blood and enter the lymphoid tissues.
Granulocyte-macropage colony-stimulating factor. It is produced
by macrophages and T cells and it stimulates growth and
differentiation of myelomonocytic lineage cells, particularly
dentritic cells. Secreted by activated TH1 and induces macrophage
differentiation in the bone marrow.
Serine proteases produced by CTLs (and NKs) that are involved
in inducing apoptosis in the target cell.
human chorionic gonadotropin, is a hormone that can be
detected in a pregnant mothers blood or urine. mABs against this
hormone allow diagnosis of pregnancy.
Human Leukocyte Antigen. So are named the MHC genes (in
human). There are three class I α-chain genes, called HLA-A,-B
and –C. There are also three pairs of MHC class II α- and β-chain
genes, called HLA-DR,-DP and –DQ.
See CLIP
The inactivated form of CAD – Caspase-Activatable DNAse.
When it is broken down by caspases it can enter the nucleus
where it cleaves DNA. Also see Bcl-2.
Intracellular adhesion molecules. Are cell surface ligands for the
leukocyte integrins and are crucial in the binding of lymphocytes
and other leukocytes to certain cells, including APC and
endothelial cells. They are members of the Ig superfamily. Are
the most prominent ligand for LFA-1. Are rapidly inducible on
endothelial cells by infections, and play a major role in local
4
ICAM-2
ICAM-3
IFN-α, -β
IFN-γ
IgA
IgD
IgE
IgG
IgM
Igα, Igβ
IL-1
IL-10
IL-12
inflammatory responses.
IntraCellular Adhesion Molecules. Are cell-surface ligands for
the leukocyte integrins and are crucial in the binding of
lymphocytes and other leukocytes to certain cells, including APC
and endothelial cells. ICAM-2 is constitutively expressed at
relatively low levels by endothelium.
See ICAM-2. ICAM-3 is expressed only on leukocytes and is
thought to play an important part in adhesion between T cells and
APC.
Cytokines (interferons) that can induce cells to resist to viral
replication. Interferon synthesis is thought to occur in response to
the presence of dsRNA. They are secreted by the infected cells
and bind to a common cell-surface receptor on both the infected
cell and nearby cells. They have three main functions: 1.to induce
resistance to viral replication in all cells. 2.to increase MHC class
I expression and antigen presentation in all cells. 3.to activate NK
cells to kill virus infected cells.
Is a cytokine that can induce cells to resist viral replication. It is a
product of CD4 TH1 cells, CD8 T cells and NK cells. Its primary
action is the activation of macrophages. Many phatogens,
specially intracellular bacteria and viruses, activate dentritic cells
and NK cells to secrete IL-12 and IFN-γ, which cause
proliferating CD4 T cells to differentiate into TH1 cells. IFN-γ
secreted from activated TH1 cells acts on TH2 cells to inhibit their
proliferation.
Is the class of immunoglobulin characterized by α heavy chains.
IgA antibodies are secreted mainly by mucosal lymphoid tissues.
Is the class of immunoglobulin characterized by δ heavy chains. It
appears as surface immunoglobulins on mature naïve B cells but
its function in unknown.
Is the class of immunoglobulin characterized by ε heavy chains.
It is involved in allergic responses.
Is the class of immunoglobulin characterized by γ heavy chains. It
is the most abundant class of immunoglobulins found in the
plasma.
Is the class of immunoglobulin characterized by μ heavy chains.
It is the first immunoglobulin to appear on the surface of B cells
and the first to be secreted.
Proteins associated with heavy chains on the B-cell surface to
form the B cell receptor (BCR).
Activates hepatocytes to synthesize acute-phase proteins, and
bone marrow endothelium to release neutrophils. Acts as a
pyrogen inducing body temperature.
Secreted by TH2 cells and acts to inhibit activation and growth of
TH1 cells.
Produced by B cells and macrophages. It activates NK cells and
5
IL-15
IL-2
☺
IL-3
IL-4
IL-5
☺
IL-6
IL-7
IL-8
IL-9
ITAM
ITIM
JAK
KAR
KIT (CD117)
Lck
☺
induces CD4 T-cell differentiation to TH1 cells.
Stimulates growth of intestinal epithelium, T cells and NK cells.
Interlukin-2. is the cytokine that is most central to the
development of an adaptive immune response. Activated T cells
express a high affinity IL-2 receptor and secrete IL-2. Binding of
IL-2 to its receptor (in an autocrine manner) signals the T cell to
enter the cell cycle and induces T cell proliferation.
Produced by T cells and thymic epithelial cells. Has a synergistic
action in early hematopoiesis. Secreted by activated TH1 and
induces macrophage differentiation in the bone marrow.
Produced by T and mast cells. Has to do with B cell activation
and with IgE switch. Suppresses TH1 cells and leads to
differentiation of CD4 T cells into TH2 cells.
Produced by T and mast cells. Mediates eosinophil growth and
differentiation.
Produced by T cells, macrophages and endothelial cells. Mediates
T and B cell growth and differentiation. Also acts similarly to IL1 (See IL-1).
Mediates growth of pre-B cells and pre-T cells.
Secreted by macrophages. Is a chemotactic factor that recruits
neutrophils, basophils and T cells to the site of infection.
Produced by T cells. Mediates stimulation of TH2 cells.
Immunoreceptor Tyrosine-based Activation Motifs. Known to be
present in the accessory chains involved in signaling from
different immune cells. ITAMs are composed of two tyrosine
residues separated by around 9-12 aa. These tyrosines are
phosphorylated by the receptor-associated Src-family tyrosine
kinases enabling to transduce a signal.
Immunoreceptor Tyrosine-based Inhibitory motif. A motif which
is found in several receptors that modulate activation signals in
lymphocytes. It functions by recruiting inhibitory phosphotases.
In this motif, a large hydrophobic residue such as isoleucine or
valine occurs two residues upstream of a tyrosine.
Janus Kinase. Is activated by the aggregation of cytokine
receptors. This kinase phosphorylate proteins known as STAT.
Killer Activatory Receptors. Receptors that can activate NK cells
to kill infected or abnormal target cells.
Stem-Cell Factor receptor. Is a transmembrane protein with an
external ligand-binding domain specific for SCF and a
cytoplasmic domain with intrinsic tyrosine kinase activity. In the
unbound state, the kinase part of the receptor is inactive. When
SCF binds to KIT, it causes the receptor proteins to dimerize; this
allows the two tyrosine kinase domains to phosphorylate one
another and to become activated.
A cytoplasmatic tyrosine kinase that interacts strongly with CD4.
6
LFA-1
LFA-3
☺
li = Invariant chain
LPS
L-selectin
Lyn
MAP kinase
MBL
MCP-1
MHC
MIC-A and MIC-B
☺
NFAT
NFκB
Leukocyte Function Antigen. A cell adhesion molecule. Is a β2
integrin. Is important in T-cell adhesion to endothelial cells and
binds to ICAM-1 (see ICAM-1).
Leukocyte Function Antigen. A cell adhesion molecule. A
member of the Ig superfamily.
Forms a complex with MHC class II, blocking the binding of
peptides and misfolded proteins. li is cleaved in an acidified
endosome, leaving a short peptide fragment, CLIP, still bound to
the MHC class II molecule.
A bacterial molecule which is first bound by LBP . LBP loads its
bound LPS onto the CD14 (on the macrophage). This then
triggers the membrane protein TLR-4 to signal to the nucleus,
activating the transcription factor NFκB, which in turn activates
genes involved in defense against infection.
Lymph node homing receptor. Expressed on naïve T cells and
guides their exit from the blood into peripheral lymphoid tissues.
See Fyn
Mitogen-Activated Protein kinases. Kinases that become
phosphorylated and activated upon cellular stimulation by a
variety of ligands, and lead to new gene expression by
phosphorylating key transcription factors.
Mannan Binding Lectin. Also called mannose-binding protein, is
an acute-phase protein that binds to mannose residues. It can
opsonize phatogens bearing mannose on their surfaces and can
activate the complement system.
A chemokine that activates macrophages, basophil histamine
production and promotes TH2 immunity.
Major histocompatibility complex. A cluster of genes on human
chromosome 6. It encodes a set of membrane glycoproteins
called the MHC molecules. The MHC class I molecules present
peptides generated in the cytosol to CD8 T cells (CTLs), and the
MHC class II molecules present peptides degraded in the
intracellular vesicles to CD4 T cells. The MHC also encodes
proteins involved in antigen processing and other aspects of host
defense. The MHC is the most polymorphic gene cluster in the
human genome, having large numbers of alleles at several
different loci.
MHC-like molecules that are expressed on intestinal epithelial
cell in response to cellular injury and stress.
Nuclear Factor of Activated T cells. A transcription factor that is
a complex of a protein NFATc (held in the cytosol) and the
Fos/Jun dimmer (AP-1). It moves from the cytosol to the nucleus
after cleavage of the phosphate residues by calcineurin. Is
important in T cell activation.
A transcription factor that is activated by signals from receptors
of the TLR family. It activates genes involved in host defense
7
NK1.1
NKG2D
☺
Perforine
P-selectin
RAG-1, -2
RAS
SCF
STAT
Syk
TAP1 and TAP2
Tapsin
TCR
☺
against infection.
A receptor commonly found on NK cells. It is also expressed by a
small subset of T cells. NK1.1+ T cells produce IL-4 (see IL-4) in
response to parasitic worms.
γ:δ T cells bearing this receptor bind to MIC-A and MIC-B, and
this enables them to induce apoptosis of an infected epithelial
cell.
A protein that can polymerize to form the membrane pores that
are an important part of the killing mechanism in the cellmediated cytotoxicity. Perforin is produced by CTLs and NKs
and is stored in granules that are released by the cell when it
contacts a specific target cell.
Upon endothelial activation by interactions with macrophage
cytokines, there is a rapid induction of externalization of granules
that contain P-selectin, which is now expressed on the surface of
the endothelial cells. Shortly after, mRNA encoding E-selectin is
synthesized, and within two hours it is mainly expressed on the
endothelial cells. Both of these proteins interact with molecules
expressed on the surface of neutrophils.
Recombination Activating Genes. Encode proteins which are
critical to receptor gene rearrangement.
A monomeric G protein that acts as an intracellular signaling
molecule downstream of many transmembrane signaling events.
Binds GTP in its active form and hydrolyzes it to GDP to become
inactive.
Stem-Cell Factor. See KIT. Plays a role in B cell maturation.
Signal Transducers and Activators of Transcription. Are
normally found in the cytosol, but move to the nucleus on
phosphorylation and activate a variety of genes. See also JAK.
A tyrosine kinase expressed mainly in hematopoietic cells. Is
recruited to the receptor upon full phosphrylation of the ITAMs
(parallel to ZAP70 which is mainly in T lymphocytes).
Transporters associated with Antigen Processing. Are ATPbinding cassette proteins involved in transporting short peptides
from the cytosol into the lumen of the ER, where they associate
with MHC class I molecules. The two TAP proteins form a
hetrodimer.
Tap-associated protein which is encoded by a gene that lies within
the MHC. Tapsin forms a bridge between MHC class I molecules
and TAP1 and TAP2, allowing the partially folded α:β2microglobulin hetrodimer to await the transport of a suitable
peptide from the cytosol.
T cell receptor. Consists of a disulfide-linked hetrodimer of the
highly variable α and β chains expressed at the cell membrane as
a complex with the invariant CD3 chains. T cells carrying this
type of receptor are often called α:β T cells. An alternative
8
TdT
TGF-β
TH1 cells
TH2 cells
TI-1 antigens
TI-2 antigens
TNF-α
TNF-β
VCAM-1
VLA-4
ZAP70
β2-microglobulin
receptor made up of variable γ and δ chains is expressed with
CD3 on a subset of T cells. both of these receptors are expressed
with a disulfide-linked homodimer of ζ chains.
Terminal Deoxynucleotidyl Transferase. Has to do with TCR and
Ig rearrangement.
Secreted by activated TH2 cells and acts to inhibit activation and
growth of TH1 cells.
Are a subtype of CD4 T cells that are characterized by the
cytokines they produce. They are mainly involved in activating
macrophages.
Are a subtype of CD4 T cells that are characterized by the
cytokines they produce. They are mainly involved in stimulating
B cells to produce antibody.
Thymus Independent antigens. At high concentrations, these
molecules cause the proliferation and differentiation of most B
cells regardless of their antigen specificity (polyclonal activation).
At low concentrations, only B cells specific for the TI-1 antigen
bind enough of it to focus its B cell activating properties onto the
B cell; this gives a specific antibody response to epitopes on the
TI-1 antigen. They can activate both immature and mature B
cells. Are often called B-cell mitogens. An example is LPS.
Thymus Independent antigens. Molecules such as bacterial
capsular polysaccharids that have highly repetitive structures.
They can activate only mature B cells
Is a cytokine produced by macropages and T cells that has
multiple functions in the immune response. Acts similarly to IL-1
and IL-6 (see IL-1).
Tumor Necrosis Factor. Also known as Lymphotoxin. A cytokine
secreted by inflammatory CD4 T cells that is directly cytotoxic
for some cells.
An adhesion molecule on stromal cells. Lymphoid progenitor
cells and pro-B cells bind to VCAM-1 through the integrin VLA4 (see VLA-4). These interactions promote the binding of the
receptor tyrosine kinase Kit (see Kit) on the surface of the pro-B
cell to SCF (see SCF) on the stromal cell, which activates the
kinase and induces the proliferation of the B cell progenitors.
Very late antigen. Member of the β1 family of integrins involved
in cell-cell and cell-matrix interactions. Lymphoid progenitor
cells and early pro-B cells bind to the adhesion molecule VCAM1 (see VCAM-1) on stromal cells through the integrin VLA-4.
The ζ chain associated protein. Is a tyrosine kinase that binds to
the phosphrylated ITAMs of the ζ chain. After binding of the coreceptor (CD4/CD8) to the MHC molecule on the APC, the Lck
is brought into the complex and phosphorylates and activates
ZAP70. ZAP70 is important in propagating the signal onward.
A chain which is part of the MHC class I. it is small and
9
γ:δ T cells
ζ (zeta) chain
noncovalently associated with the other chains. It is not
polymorphic and is not encoded within the MHC locus. It does
not span the membrane.
Subtype of T cells that are especially abundant in the gut mucosa.
Some of them express the NKG2D receptor.
One of the invariant accessory chains of the TCR which is present
as a largely intracytoplasmic homodimer. It has three ITAMs in
its cytoplasmic domain.
!!!!‫בהצלחה‬
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