Term
| Molecules that communicate among cells of the immune system are referred to as _____ |
|
Definition
|
|
Term
| The interaction of a cytokine with its receptor on a target cell can cause changes in the expression of |
|
Definition
| adhesion molecules and chemokine receptors on target membranes allowing it to move from one location to another |
|
|
Term
| Besides movement, cytokines can also signal immune cells to |
|
Definition
| increase or decease the activity of an enzyme or change its transcriptional program...so alter its and enhancing its effector functions. |
|
|
Term
| A third thing that cytokines can do? |
|
Definition
| instruct a cell when to die and when to survive. |
|
|
Term
| the modern way cytokines are classified....and name 2 old names. |
|
Definition
by Mode of Action
classified on the basis of the distance between the cell secreting the
signaling ligand and the cell receiving the chemical signal.
TNF and interferon are interleukins |
|
|
Term
| a sub group of cytokines whose specific purpose is mobilization |
|
Definition
|
|
Term
|
Definition
They act at chemoattractants to attract cells by influencing the assembly, disassembly, and
contractility of the cytoskeleton and cell surface receptors. |
|
|
Term
| Most immune system cytokines exhibit ____ and/or _____ action |
|
Definition
|
|
Term
| Only a few cytokines exhibit endocrine action.. what is endocrine action? |
|
Definition
| pass from producer cell to target cell via the blood stream |
|
|
Term
| Target cell activity or state changes. |
|
Definition
• Proliferation
• Differentiation
• Change in gene expression
• Cell Death
• Movement |
|
|
Term
Cytokines Mediate Activation, Proliferation, and
Differentiation of Target Cells |
|
Definition
1. Cytokine producing cells respond to stimuli to upregulate the expression of cytokine genes.
2. Cells express/secrete cytokine proteins.
3. Cytokines bind specific receptor proteins on target cells.
4. Signaling pathways are triggered in target cells.
5. Target cell activity or state changes.
• Proliferation
• Differentiation
• Change in gene expression
• Cell Death
• Movement
6. Cytokines regulate the intensity and duration of
the immune response. |
|
|
Term
The IL-1 Family of Cytokines
Includes IL-1a, IL-1b, IL-1Ra, IL-18, IL-18BPand IL-33
Secreted very early in the immune response by dendritic cells, monocytes, or
macrophages. |
|
Definition
|
|
Term
Antibody to the _______
tumor necrosis factor (TN) alpha is used to downregulate the
immune response for the treatment of a variety of autoimmune diseases |
|
Definition
|
|
Term
| lymphokines, monokines, interleukins, and chemokines are ____ |
|
Definition
|
|
Term
| Cytokines are ____, which means that one cytokine can act on multiple cells and have multiple functions. |
|
Definition
pleiotropic
they can also be redundant For
example, IL-2, IL-4, and IL-5 can induce B-cell proliferation.
Their action can be synergistic Interferon gamma (INF) and TNF in combination can greatly
increase the expression of MHC class I molecules on different
cell types. |
|
|
Term
cytokines can also be ____, the action of one cytokine having the opposite effect of
the action of another cytokine. For example, INF can induce
the activation of macrophages whereas IL-4 inhibits it. |
|
Definition
|
|
Term
_____ is the ability of a cytokine to bind to one
cell and to induce that cell to secrete additional cytokines |
|
Definition
|
|
Term
| General Properties of Cytokines and Chemokines What chapter 4 covers |
|
Definition
■ Six Families of Cytokines and Associated Receptor Molecules
■ Cytokine Antagonists
■ Cytokine-Related Diseases
■ Cytokine-Based Therapies |
|
|
Term
Although a variety of cells can secrete cytokines that instruct
the immune system, the principal producers are _________ |
|
Definition
TH cells,
dendritic cells, and macrophages. |
|
|
Term
| Cytokines released from these cell types are capable of activating entire networks of interacting cells . Among the numerous physiological responses that require cytokine involvement are the ___________ |
|
Definition
generation of cellular and humoral immune responses, the
induction of the inflammatory response, the regulation of
hematopoiesis, and wound healing. |
|
|
Term
cytokines rarely, if ever, act alone. Instead, a target cell is exposed to a
milieu containing a mixture of cytokines whose combined _________
effects can have a wide variety of
consequences. Plus, cytokines often induce the synthesis of other cytokines, resulting in cascades of activity. |
|
Definition
| synergistic or antagonistic |
|
|
Term
____ secrete cytokines that promote the differentiation and activity of macrophages and cytotoxic T cells, thus leading to a primarily cytotoxic immune response, in
which cells that have been infected with viruses and intracellular bacteria are recognized and destroyed. |
|
Definition
|
|
Term
The cytokines IL-12 and interferon (IFN) ¥ induce TH1 differ-
entiation. |
|
Definition
|
|
Term
_____ activate B cells to make
antibodies, which neutralize and bind extracellular pathogens, rendering them susceptible to phagocytosis and
complement-mediated lysis |
|
Definition
TH2 cells
IL-4 and IL-5 support the gen-
eration of TH2 cells. |
|
|
Term
| TH17 cells promote the differentiation of activated macrophages and neutrophils, and support the inflammatory state; their generation is induced by ____ |
|
Definition
|
|
Term
| Differentiation and activity of each T-cell subpopulation is supported by the binding of different combinations of ___to T-cell surface receptors, with each cytokine combination inducing its own characteristic array of intracellular signals, and sending the helper T cell down a particular differentiation pathway |
|
Definition
|
|
Term
| The cytokines IL-12 and interferon (IFN) ¥ induce ____________ |
|
Definition
|
|
Term
| Interleukin 1 (IL-1) cytokine of innate immunity |
|
Definition
secreted by Monocytes, macrophages,
endothelial cells, epithelial cells that target asculature (inflammation); hypothalamus (fever); liver (induction of
acute phase proteins) |
|
|
Term
Tumor necrosis factor- (TNF-)
cytokine of innate immunity |
|
Definition
Secreted by Macrophages, monocytes,
neutrophils, activated T cells and
NK cells../target cells Vasculature (inflammation); liver (induction of acute phase proteins); loss of muscle, body fat (cachexia); induction of death in many cell types; neutrophil activation |
|
|
Term
Interleukin 12 (IL-12)
cytokine of innate immunity |
|
Definition
| secreted by macrophages, dendritic cells target cells =NK cells; influences adaptive immunity (promotes TH1 subset |
|
|
Term
Interleukin 6 (IL-6)
cytokine of innate immunity |
|
Definition
| secreted by Macrophages, endothelial cells, and TH2 cells target =Liver (induces acute phase proteins); influences adaptive immunity (proliferation and antibody secretion of B-cell lineage) |
|
|
Term
Interferon- (IFN-alpha) (this
is a family of molecules) |
|
Definition
secreted by Macrophages dendritic cells, virus-infected cell/ target Induces an antiviral state in most nucleated cells; increases MHC Class I
expression; activates NK cells
cytokine of innate immunity |
|
|
Term
IFN beta
cytokine of innate immunity |
|
Definition
secreted by macrophages, dendritic cells, virus-infected cells / target Induces an antiviral state in most nucleated cells; increases MHC Class I
expression; activates NK cells |
|
|
Term
Interleukin 2 (IL-2)
cytokine of adaptive immunity |
|
Definition
| secreted by T cells/ target: T-cell proliferation; can promote AICD. NK cell activation and proliferation; B-cell proliferation |
|
|
Term
Interleukin 4 (IL-4)
cytokine of adaptive immunity |
|
Definition
| Secreted by TH2 cells, mast cells/ Target =Promotes TH2 differentiation; isotype switch to IgE |
|
|
Term
Interleukin 5 (IL-5)
cytokine of adaptive immunity |
|
Definition
| secreted by TH2 cells/ target Eosinophil activation and generation |
|
|
Term
Transforming growth factor (TGF-)
cytokine of adaptive immunity |
|
Definition
secreted by T cells, macrophages,
other cell types/ target=Inhibits T-cell proliferation and effector functions; inhibits B-cell
proliferation; promotes isotype switch to IgA; inhibits macrophages |
|
|
Term
Interferon (IFN-)
cytokine of adaptive immunity |
|
Definition
| secreted by TH1 cells, CD8 cells, NK cells/ target Activate macrophages; increases expression MHC Class I and Class II molecules; increases antigen presentation |
|
|
Term
During T-cell activation by an antigen-presenting dendritic cell, or of B-cell activation by a cognate T cell,
the respective pairs of cells are held in close juxtaposition __ |
|
Definition
for many hours..while the cells
release cytokines that bind to relevant receptors on the partner cell surface, without ever entering the general circulation |
|
|
Term
| the cytokines are released right at the region of the___ that is in closest contact with the recipient cell |
|
Definition
|
|
Term
the close cell-to-cell, directional release of cytokines by the secretory apparatus means that the effective concentration of cytokines in the
region of the membrane receptors may be orders of magnitude ___than that experienced outside the contact region of the two cells. |
|
Definition
|
|
Term
cytokines usually act for only a
__________. |
|
Definition
| limited time and over a short distance |
|
|
Term
| Effector molecules such as cytokines can bind to____, and receptors can bind to more than one signaling molecule |
|
Definition
|
|
Term
Effector molecule signaling can
also cooperate with signaling through ______. |
|
Definition
| antigen-specific receptors |
|
|
Term
the goal of the chapter is to outline
some general principles of cytokine and receptor architecture/ function |
|
Definition
| to you to place any cytokine into its unique biological context |
|
|
Term
The science of ___ has
been extended to address the mapping of proteins that are secreted by various cell types. The array of proteins secreted by a
cell is referred to as its ___, and can be more formally defined
as the “proteins released by a cell, tissue, or organisms through classical and nonclassical secretion mechanisms.” |
|
Definition
|
|
Term
| interest in the concept of the secretome as a way to diagnose and identify various types of ___. |
|
Definition
|
|
Term
Expression of a common ¥ chain defines the __receptor subfamily. This subfamily includes receptors
for IL-2, IL-4, IL-7, IL-9, IL-15, & IL-21. |
|
Definition
|
|
Term
The IL-2 receptor is a heterotrimer, which consists of an
___ chain. |
|
Definition
| α β γ (alpha, beta, gamma) |
|
|
Term
The ___ chains form the pocket for binding IL-2.
Alpha stabilizes the binding. The γ chain functions as
the signal transducing subunit. |
|
Definition
|
|
Term
| One form of the severe combined immunodeficiency(SCID) is caused by a defect in the |
|
Definition
|
|
Term
| IL-2 receptor occurs in three forms: __ |
|
Definition
| low affinity, intermediate affinity, and high affinity. |
|
|
Term
Low affinity contains an α chain and cannotsignal. It is expressed on activated T and B cells.
It may act as a “sink” for __. |
|
Definition
|
|
Term
Intermediate affinity is dimeric
(β γ chains) and
does signal. It is expressed on resting __________ |
|
Definition
|
|
Term
| High affinity is trimeric ( α β γ chains) and does signal. It is expressed on activated ______ |
|
Definition
|
|
Term
| Interferon Family of Cytokines |
|
Definition
|
|
Term
|
Definition
•Interferons-α (20 members) and interferon-β .
•Secreted by macrophages, dendritic cells, and virally infected cells. |
|
|
Term
|
Definition
•Interferon- γ
•Produced by activated T and NK cells.
•Modulates the adaptive immune response
•Drives T helper cells toward the TH1 phenotype
•Promotes activation of macrophages
•Promotes differentiation of T cytotoxic cells. |
|
|
Term
|
Definition
interferon receptors and promotes
receptor dimerization and activation.
Associated Janus kinases (JAKs) become activated.
JAKs phosphorylate tyrosine residues on the receptor,
providing docking sites for STAT proteins.
JAK then phosphorylates STAT.
Activated STAT dimerizes and moves into the nucleus where is regulates gene expression. |
|
|
Term
| Versatility of the JAK/STAT Pathways |
|
Definition
| There are several JAKs and several STATs and they associate with a variety of cytokine receptors. |
|
|
Term
| Specific receptors bind to specific partner JAKs which activate unique ___. |
|
Definition
|
|
Term
| Particular STAT homodimers and heterodimers recognize very specific and different ___, therefore they can only activate a specific subset of target genes. |
|
Definition
|
|
Term
The Tumor Necrosis Factor Family of Cytokines
Regulates the development, effector function, and homeostasis
of cells participating in the ___.
TNF cytokines can be membrane bound or soluble |
|
Definition
| skeletal, neuronal, and immune systems |
|
|
Term
Soluble TNFa is a pro-inflammatory cytokine produced by
macrophages, lymphocytes, fibroblasts, and keratinocytes
in response to infection. It binds to receptors on the
surface of ___________________ |
|
Definition
| neutrophils, endothelail cells, and osteoclasts |
|
|
Term
Active forms of TNF cytokines form homotrimers or heterotrimers.
Signaling through the TNF receptors can lead to pro- or antiapoptotic
outcomes depending on the nature of the signal. |
|
Definition
The survival versus death decisions that are made at the level of
the TNF receptor depend upon the outcome of the race between
the generation of active caspase-9 or the generation of the
caspase-8 inhibitor (cFLIP).
How the cell integrates these opposing signals is not understood. |
|
|
Term
| The IL-17 Family of Cytokines |
|
Definition
Typically promote inflammation
• IL-17 receptors are found on neutrophils, keratinocytes, and other nonlymphoid cells.
• Operate at the interface between innate and adaptive immunity.
• TH17, a new lineage of T helper cells that secrete IL-17.
• Coordinate the release of proinflammatory and neutrophil mobilizing cytokines. |
|
|
Term
| Eight (8) different IL-17 family members have a highly conserved structure with four key____. Five different receptor proteins that are arranged as homodimers or heterodimers. |
|
Definition
|
|
Term
IL-17 Receptor Signaling :
Three pathways are initiated when IL-17 binds to its receptor. Name them. |
|
Definition
1. TRAFs recruit TAK complex with
associated TAB proteins. This complex
activates NFkB.
2. TRAFs also activate the MAP kinase
pathway.
3. leads to activation of the
C/EBP transcription factor family which
up regulates the expression of IL-6. |
|
|
Term
| The Chemokine Family of Cytokines |
|
Definition
Small cytokines that bind to cell surface receptors and induce the movement of leukocytes up a concentration gradient and toward the chemokine source (chemotaxis).
• Structurally homologous
• Tertiary structure is defined by a highly conserved disulfide bonds between cysteine residues.
• Position of the cysteine residues determines the classification of the chemokines into 6 different structural categories which also have functional significance. |
|
|
Term
| What determines the classification of the chemokines into 6 different structural categories which have functional significance. |
|
Definition
| Position of the cysteine residues |
|
|
Term
| MORE on the chemokine family of cytokines |
|
Definition
Chemokine receptors are heterotrimeric, G-protein coupled receptors.
• They are classified according to the type of chemokine that they bind.
• Different chemokines induce different
signaling pathways. |
|
|
Term
| Viruses Can Exploit Cytokine Activity |
|
Definition
can generate viral products that interfere with cytokine secretion.
• can generate cytokine homologs that compete with natural cytokines or inhibit anti-viral responses.
• They produce soluble cytokine binding proteins
• They express homologs of cytokine receptors.
• They produce proteins that interfere with intracellular signaling.
• They induce expression of natural cytokine inhibitors. |
|
|
Term
| Viruses Can Exploit Cytokine Activity |
|
Definition
can generate viral products that interfere with cytokine secretion.
• can generate cytokine homologs that compete with natural cytokines or inhibit anti-viral responses.
• They produce soluble cytokine binding proteins
• They express homologs of cytokine receptors.
• They produce proteins that interfere with intracellular signaling.
• They induce expression of natural cytokine inhibitors. |
|
|
Term
| Cytokine-Related Diseases |
|
Definition
|
|
Term
|
Definition
• overwhelming bacterial infections (S. aureus, E. coli, K. pneumoniae, P
aeruginosa, E. aerogenes, & N. meningitidis)
• Caused by trauma
• Most common cause of death in the US hospital intensive-care units
• Over-whelming production of pro-inflammatory and fever-inducing cytokines such as TNF and IL-1.
• Alterations in body temperature, respiratory rate, white blood cell count, capillary leakage, tissue injury, widespread blood clotting, organ system failure.
• Bacterial cells that have endotoxins bind to Toll-like receptors on surface of macrophages and dendritic cells and cause them to produce IL-1 and TNF |
|
|
Term
| Bacterial cells that have endotoxins bind to______ |
|
Definition
| Toll-like receptors on surface of macrophages and dendritic cells and cause them to produce IL-1 and TNF |
|
|
Term
|
Definition
• Can be induced by viral infections.
• Extremely high levels of cytokines are produced.
• Creates shock like symptoms
• Associated with the 1918 Spanish Influenza and the severe acture respiratory syndrome (SARS) epidemic in 1993 |
|
|
Term
|
Definition
| Chimeric TNF receptor/IgG constant region |
|
|
Term
|
Definition
monoclonal antibody against TNF α
receptor.. |
|
|
Term
|
Definition
| Members of this family may be either soluble or membrane bound; they are involved in immune system development, effector functions, and homeostasis |
|
|
Term
Cytokines of the interleukin ____ family are typically
secreted very early in the immune response by dendritic cells
and monocytes or macrophages. IL-1 secretion is stimulated
by recognition of viral, parasitic, or bacterial antigens by innate immune receptors. |
|
Definition
|
|
Term
proinflammatory, meaning ___ In addition, IL-1 has systemic
(whole body) effects and signals the liver to produce acute phase proteins such as the Type I interferons (IFNs α and β), IL-6, and the chemokine CXCL8. These proteins further
induce multiple protective effects, including the destruction
of viral RNA and the generation of a systemic fever response
. IL-1 also activates both T and B cells at the induction of the adaptive immune response. |
|
Definition
meaning that they induce an increase in the capillary permeability at the site of cytokine secretion,
along with an amplification of the level of leukocyte migration into the infected tissues. |
|
|
Term
Significant homology in the _______of hematopoietin family cytokines defines them as members
of a single protein family, despite a relatively high degree of
amino acid sequence diversity. |
|
Definition
| three-dimensional structure |
|
|
Term
Congenital X-linked severe combined immunodeficiency (XSCID) results from a defect in the γ-chain gene, which maps to the X chromosome. The immunodeficiency observed in this
disorder, which includes deficiencies in both___, results from the loss of all the cytokine functions mediated by the IL-2 subfamily receptors. |
|
Definition
| T-cell and NK-cell activity |
|
|
Term
Subfamilies of hematopoietin
family cytokine receptors share
common subunits |
|
Definition
¥=IL-2, IL-4, IL-7, IL-9, IL-15, IL-12
β=IL-3, IL-5, GM-CSF
gp130=IL-6, IL-11, LIF, OSM, CNTF, IL-27 |
|
|
Term
Members of the ___Cytokine Family Can
Signal Development, Activation, or Death |
|
Definition
|
|
Term
At the close of an immune response, when the pathogen is gone and needs to eliminate the extra lymphocytes .. lymphocytes begin to express the TNF
family receptor _____ |
|
Definition
| Fas on their cell surfaces. |
|
|
Term
Fas, and its ligand
Fas, are specialized members of the TNF receptor and the
TNF cytokine families, respectively, and they work together
to promote ___________ |
|
Definition
|
|
Term
The complex of Fas, FADD, and procaspase-8 is
referred to as the _______ |
|
Definition
Death-Inducing Signaling Complex
(DISC). |
|
|
