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Kuby Immunology 4
Kuby Immunology ch 4 another try
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Biology
Undergraduate 4
02/18/2014

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Term
Cytokines:
Definition
Molecules that communicate among
cells of the immune system. Molecules that communicate among cells of the
immune system are referred to as cytokines.
Term
name the things cytokines do
Definition
Soluble and membrane bound forms
• Bind to target receptors
• Promote changes in surface adhesion
molecules
• Promote changes in signaling, metabolic processes, and gene expression
• Can regulate cell death and proliferation
Term
cytokines include _____ that communication between WBC.
Definition
Includes interleukins—proteins that
communicate between white blood cells.
Term
what do chemokines do?
Definition
Chemokines: Subpopulation of cytokines that mobilize immune cells from one organ to another or one part of an organ to another.
They act at chemoattractants to attract cells by influencing the assembly, disassembly, and
contractility ofthe cytoskeleton and cell surface receptors.
Term
Classification of Cytokines by Mode of Action
name the modes of action of cytokines
Definition
Most cytokines use autocrine and/or paracrine modes of action Only a few cytokines exhibit endocrine action...like Interleukin-2
Term
the biological effect of cytokines can be
Definition
Term
which is a cytokine that uses all three modes of action
Definition
the T-cell interleukin IL-2 acts
effectively in all three modes
Term
What do cytokines do to target cells
Definition
Cytokines Mediate the Activation, Proliferation,
and Differentiation of Target Cells
Term
Cytokines regulate the intensity and duration of the immune response
Multiple actions of cytolines are
Definition
Cytokines exhibit the attributes of pleiotropy, redundancy, synergism, antagonism, and cascade induction
Term
Pleiotrope =
Redundancy=
Synergy =
antagonism=
Definition
one can do many thing
Many do the same thing
some cooperate together
som turn on or off others
Term
functional groups of some cytokines...
IL 1 is secreted by _______
Targets and effects _____________
Definition
monocytes, macrophages, endohelial cells, epithelial cells
targets vascularature (inflammation) hypothalamuch (fever), liver (inducion of acue phase proteins )
Term
Tumor necrosis factor TNF alpha
secreted by____
targets and effects _______
Definition
macrophages, monocytes, neutrophils, activated T cells and NK cells.
vasculature (inflammation); liver (induction of acute phase ) proteins ) loss of muscle, body fate, induction of death in many cell types, neutrophil activation
Term
IL 12
Definition
secreted by macrophages, dendritic cells....targets NK cells, influences adaptive immunity (Promotes TH1 subset)
Term
IL6 secreted by ______
Targets _____
Definition
macrophages, dendritic cells... targets liver (induces actue phase proteins ) influneces adaptive aimnnnity and anibody secretions
Term
In order for a cell to respond to a signaling molecule, it
must express ______________ for that molecule
Definition
receptors
Term
Hematopoietin (Class I) Family Cytokines Share
_________Motifs, but
Induce a Diversity of Functions in Target Cells
Definition
Three-Dimensional Structural
Term
the IL-1 family includes
Definition
Includes IL-1alpha, IL-1beta, IL-1Ra, IL-18, IL-18BP and IL-33
Term
The IL-1 is secreted early on by ________
Definition
dendritic cells, monocytes, or
macrophages.
Term
All but _____is pro-inflammatory—increase capillary permeability and
amplify the level of leukocyte migration into infected tissues.
Definition
IL-1Ra
Term
Acute phase response—induces _______________
Definition
the liver to make the acute phase proteins.
Term
IL-1alph is _____ _____. IL-1b, IL-18, and IL-33 are made as pro-forms that
undergo proteolytic processing by caspase. They are then secreted by cells.
Definition
membrane bound
Term
sTILL IN IL-1 familty...IL-33 is secreted by_____________, and
lung/skin fibroblasts. Implicated in asthma and inflammatory airway and
bowel diseases.
Definition
smooth muscle cells and the bronchial epithelial cells
Term
IL-1Ra acts as an _____of IL-1 and prevents its binding to its receptor,
but doesn’t send a signal.
Definition
antagonist
Term
still IL-1 familty IL-18 BP acts as an antagonist that binds to IL-18 directly and keeps it from_____
Definition
binding to its receptor.
Term
IL-1 Receptors IL-1, IL-18, and IL-33 have _____. IL-1 and IL-33 receptors are heterodimers that include the IL-1RAcP. IL-18 receptors have both an alpha and beta chain.
Definition
unique receptors
Term
IL-1 signaling IL-1 binding to its receptor induces a conformational
change in the ____________ domain that allows for the binding of MyD88.
Definition
Toll-IL-1R (TIR)
Term
IL - 1 signaling The IRAK/TRAF6 complex dissociates from the
receptor and interactions with TAK/TAB1/TAB2 omplex.
This allows for recruitment of a ubiquitin ligase, which
mono-ubiquitinates the complex and activates it.
The activated complex then targets the NFkB and MAP
Kinase pathways for activation.
These pathways activate the _____
transcription factors,modulates
the expression of proinflammatory
genes.
Definition
NFkB
and AP-1,
Term
Hematoppietin family of cytokines
functions?
Definition
Diverse...regulating proliferation to differentiation...some but not all are involved in hematopoiesis
Term
What does the hematopoietin family of cytokines share?
Definition
homology in 3D structure 4 helix bundle motifs organized into 4 anti-parallel helices..
members are divided based on helical length... They share a cp,,pm rece[tpr sibimot
Term
subunits of Hematopoitin Famile are
Definition
β = IL 2, 4 7 9 15 12
¥ = IL 3 5 GM-CSF
GP130 = IL 6 1 LIF OSM CNTF, IL-27
Term
IL-2 and receptors What defines the IL2 receptor subfamily?
Definition
A common ¥ chain includes receptors for IL-2, 4, 7, 9 15 21
Term
the IL-2 receptor is a heterotrimer consists of what chains?
Definition
Α β ¥ chains
Term
what forms the pocket for binding IL-2
and which the finding? and which the signal?
Definition
beta gamma are pockets for binding IL-2
Alpha stabilizes binding
Gamma is the tranducing subunit.
Term
one form of the sever combined immunodificiency is caused by a defect in__
Definition
the gamma chain of the IL-2 receptor (which is part of the pocket for binding IL-2)
Term
the IL2 receptor has 3 forms what?
Definition
low affinity on T and B (- signal)
Intermediate affinity on T and NK + signal
Hight trimeric + signal T and B cell
Term
interferon family of cytokines what are the types?
Definition
Type 1 alpha and beta secreted by macroph. dentritic, and viral sick cells. //type 2 , gamma from T and NK .. modulates adaptive response drives Th to TH1...promotes macrophages and T C cells.
Term
Interferon binds to receptors the associated _____become activated
Definition
JAKs whch then PHOS. to STAT STATE regulates gene expression
Term
TNF regulates?
Definition
development, effector functions and homeostasis of cells in skeletal, neuronal immune system
Term
TNF alpha is produced by
Definition
macs lymphocytes fibroblasts keratinocytes from infection...
Term
TNF alpha binds to
Definition
nutorphils, endothelial cells osteoclasts
TNF alpha can kill or not kill
Term
TNF alpha life and death decisions depends on
Definition
race between making of active casperase 9 or makking of casperase 8 inhibitor (cFlip"
Term
IL 17 family are on what
Definition
neutrophils , keratinocytes and nonlymphoid cells
Term
What operates at the interface between innate and adaptive immunity?
Definition
IL-17 family
Term
How are cytokines, interleukins, similar or different?
Definition
structure ..cytokines exhibit
autocrine and/or paracrine action; fewer exhibit endocrine
action...
Term
2.What modes of action are associated with cytokines?
Definition
leiotropic action, whereas two or
more cytokines that mediate similar functions are said to be
redundant. Cytokine synergy occurs when the combined
effect of two cytokines on cellular activity is greater than the
additive effects of the individual cytokines. In some cases,
the effects of one cytokine inhibit or antagonize the effects
of another. Cascade induction occurs when the action of
one cytokine on a target cell induces that cell to produce one
or more additional cytokines.
Term
3.What mode of action is associated with IL-2?
Definition
proliferative hematopoietin intermediate high low affinity.. acts in all 3 modes paracrine, hormone, autocrine secreted by
activated T cells.
Term
4.Interleukin-1 is a cytokine that creates systemic responses such as fever. What mode of action do you think will be associated with interleukin-1?
Definition
Term
5.What effects do cytokines have on target cells?
Definition
Term
6.Differentiate pleiotropy, redundancy, synergy, and antagonism with respect to cytokines
Definition
Term
7.Explain why IL-4 is pleiotropic, redundant, synergistic, and antagonistic.
Definition
Term
8.What cells are targeted by IL-4?
Definition
TH2 cells and mast cells for B-cell proliferation. IgE production
Term
9.IL-1, TNF-alpha, and Interleukin-6 are cytokines of innate immunity. Why? What cells produce them? What is their target?
Definition
They are all about innate cells such as macrophages
Term
10.IL-2, IL-4, IL-5 are cytokines of adaptive immunity. Why? What cells produce them? What is their target?
Definition
ARE FROM TH1 cells, CD8 + cells, NK cells//They activate or promote or inhibit//Hematopoietin (Class I) Family with short helixes/ large family of small cytokine molecules exhibits
striking sequence and functional diversity.
Term
IL-1 Family of Cytokines
a.
b. What cells make them?
c. What effects to they have on targets?
d. What are their receptors?
e. Describe the associate signaling pathway
Definition
IL-1 first noninterferon cytokine to be identified.
Members of this family include important inflammatory mediators//
dendritic cells, monocytes, or
macrophages make them...
Term
1Hematopoietin Family of Cytokines structure
Definition
Defining structure: 4 helix bundle motifs organized into four anti-parallel helices. Members are further defined based on helical length.
Term
Interferon Family of Cytokines
a. What is the difference between type I and type II interferons
b. What are the key members?
c. What cells make them?
d. What are their targets?
e. How do they signal? What is unique about their signaling pathway?
Definition
Type 1 = IFN-α, IFN-β and IFN-ω.[
Type 2 =IFN-γ.
JAK-STAT pathway, conserved cysteine residues
Term
1Tumor Necrosis Factor Family of Cytokines
a. What are their key members?
b. What cells make them?
c. What kinds of effects do they have on targets?
d. What signaling pathways are associated with them?
Definition
TNF-, TNF-, CD40L, Fas (CD95), BAFF, APRIL, LTWhile the IFNs have important roles in anti-viral responses,
all are important modulators of immune responses.Whether membrane-bound or in soluble form, active
cytokines of the TNF family assemble into trimers
Term
IL-17 Family of Cytokines
a. What are the key members?
b. What cells make them?
c. What kinds of effects do they have on targets?
d. What is unique about their receptors?
e. How do they signal?
Definition
Activated memory T cells make them to Promotes T cell proliferation..IL-17 (IL17-A), IL17B, C, D, and F ..
Term
16. The Chemokine Family of Cytokines
a. What are their key members
b. How are they structurally similar or different?
c. What cells make them?
d. What effects do they have on their targets?
e. What is unique about their receptors?
f. How do they signal?
Definition
Term
Describe different strategies used by viruses to evade cytokine-mediated immune mechanisms.
Definition
Blocks interferon-induced JAK/STAT signaling.. generation of cytokine homologs that compete.production of soluble cytokine-binding proteins..t interfere with
intracellular signaling
Term
1What is sepsis?
Definition
A Cytokine-Related Diseases
• Caused by overwhelming bacterial infections • 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
1What is a cytokine storm?
Definition
A cytokine related disease THAT Can be induced by viral infections.
• Extremely high levels of cytokines are produced.
• Creates shock like symptoms
• Associated with the 1918 Spanish Influenza and SARS epidemic in 1993
Term
How are cytokines used therapeutically? What diseases are currently being treated by cytokines?
Definition
anti–TNF-
Term
Most cytokines use the ____pathway to transmit signals, but IL-1 uses a much more complex pathway (PNAS, 2001).
Definition
Jak-STAT
Term
Cytokines regulate the innate immune system: _______. They also regulate the adaptive immune system, ___ immune responses
Definition
NK cells, macrophages, and neutrophils
the T and B cell
Term
____ are the messengers of the immune system
Definition
Cytokines
Term
___ is a T cell growth factor
Definition
IL-2
Term
Interleukin-12 (IL-12) is a very exciting cytokine. It is a heterodimeric protein that promotes _____and is a growth factor for B cells
Definition
NK and T cell activity
Term
Some cytokines are secreted following stimulation of the
innate immune system (e.g., IL-1, TNF-, CXCL8),
Definition
IL-1, TNF alpha, IL-6, Interferon alpha and beta, IL-12
Term
what are chemokines?
Definition
cytokine refers to all molecules that
communicate among immune cells,
the name chemokine
is used specifically to describe that subpopulation of
Term
the one IL-1 that is not inflammatory
Definition
IL-1Ra
Term
Key players of IL-1 family
What are the key members and how are they related structurally?
Definition
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. IL-1α and IL-1β are the most studied / their antagonist IL-1Ra/ pathogenesis of fever/ 12-stranded beta-sheet structure //soluble and membrane-bound/
Term
The _____ superfamily has 11 members, which have similar gene structure, IL-1α, IL-1β, IL-1Ra and IL-1 included all members of IL-1 cytokine family. /The old IL-1 members were renamed to IL-1F1, IL-1F2, IL-1F3 and IL-1F4
Definition
interleukin-1
Term
Hematopoietin Family ..What are their key members ?
b. What cells make them?
c. What kind of effects do they have on targets?
d. What are their receptors?
e. Describe the structure of the different forms of the IL-2 receptor and the significance of the different forms.
f. What IL-2 receptor mutation causes SCID?
Definition
2-7 12-15
Term
IL-1, TNF-alpha, and Interleukin-6 are they innate or adaptive?
Definition
IL 1 TNF and IL-6 are innate
Term
IFN-gamma
Definition
secreted by TH1 cells, CD8  cells, NK cells is a cytokine of the adaptive immune system Activates macrophages; increases expression MHC Class I and Class II
molecules; increases antigen presentation
Term
Interferon alpha and beta
Definition
secreted by Macrophages dendritic cells, virus-infected cells and is part of the innate immune system
Term
superantigen can do what in
bacterial toxic
shock and food poisoning. Included among these bacterial
superantigens are several enterotoxins, exfoliating toxins,
and toxic shock syndrome toxin (TSST1
Definition
simultaneously activate all T cells bearing a particular V domain. Because of their unique binding ability, superantigens can activate large numbers of T cells irrespec-
tive of the antigenic specificity of their canonical antigenbinding site.
Term
TNF have to do with death of cells
Definition
Fas-bearing cells are eliminatedby apoptosis.
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