Cytokines Flashcards
define CYTOKINES…?
Low molecular weight, soluble proteins Produced in response to microbes and other antigens/ Used for cellular communications
IFN-gamma …….NK,TH1,MQ and ……… b-cells,TH2
Activate/inhibit
They are involved in all aspects of the innate and adaptive immune response including:
Inflammation
• Cellular growth and differentiation
• Repair.
The cytokine do all the work is called…..
Pleiotropism
More than one cytokine do the same work……
Redundancy
Complete each others work…
Synergy
Stop each others work…..
Antagonism
Cytokines initiate their actions by binding to specific membrane receptors on target cells (………….,…………. or……………..)
autocrine, paracrine or endocrine manner
They may act in a………… manner
Cascade
……….is when the cell working on herself
………is when the cell working on niehboring cells
……….. is when the cell working on far organs
Autocrine
Paracrine
Endocrine mannar
There are three functional categories of cytokines
regulate innate IR
regulate adaptive IR→ cmir+hmir+↓of Ir
stimulate hematopoiesis(bm)
Regulators of innate immunity
(Proinflammatory) from innate cells
Tnf-a,IL-1,IL-6, IL-8
IL-12 + type 1 interferons
Regulators of adaptive immunity
CMIR→(th1)»IL-2,TNF-b, Type ll IFN
HMIR →IL-4, IL-5, IL-13
Inhibition of IR →IL-10, TGF-b
Stimulators of hematopoiesis(BM)
SCF ,CSFs, IL-3, IL-7
Innate Immune Responses
• Produced primarily by…………… () and…………. cells
Produced primarily in response to
PAMPs such as……
Can also be produced by..…………,………
MQ +dendritic/ LPS
T lymphocytes +NK cells
Most act on…………. and the
endothelial cells lining blood vessels in
order to promote and control the early
inflammatory response.
leukocytes
Regulators of innate immunity (TNF-α)produced by…………./………../…….
It is the principle cytokine that mediates………. inflammation
In excessive amounts it also is the principal cause of systemic complications such as the…………….
MQ /dendritic cell/TH1
Acute
shock cascade
TNF-a At low concentration
Acts on endothelial cells to stimulate……………… and……………
• Activates………….,………… and………
• Stimulates endothelial cells and MQ to produce ……
• Stimulates the…… to produce acute phase proteins.(IL-1)
Stimulates the synthesis of collagen in………..……..and.
……………..
• Interacts with the hypothalamus to induce…….. (endogenous pyrogen). (IL-1)
Inflammation & coagulation
Neutrophils & MQ&dendritic cells
Chemokines
Liver
wound healing+ tissue repair
Fever
TNF-a is………. for some tumor cells
cytotoxic
Interleukin-1 (IL-1)
Produced by……,……..,………..
Similar to TNF-α and works………….. with it as a mediator of the acute inflammatory response
•It stimulates activation of……lymphocytes and
………….release.
•It stimulates proliferation of…. lymphocytes.
MO ,MQ, dendritic cells
synergistically
T / IL-2
B
IL-6
Produced by?……..,…….,……
Action?…………………………………………..,
Activates……………. cells and………….
• Stimulates the proliferation of…. lymphocytes.
TH2,MQ,endothelial cells
stimulates the liver to produce acute phase protein (strongest)
Endothelial &neutrophils
B
Chemokines
Chemoattractant cytokines that enable the migration of…………. from the blood to the…………. at the site of inflammation.
They are key mediators of………….
Chemokines are produced by many cells including…………………………….
leukocytes/tissues
inflammation
macrophages, endothelial cells, some epithelial cells, T cells and fibroblasts
Alpha-chemokines
have two adjacent cysteines separated by another amino acid (Cys-X-Cys; C-X-C). They attract:: (MNND) مندي ……………………………….. e.g IL-….and……….
Beta-chemokines:
have two adjacent
cysteines (Cys-Cys; C-C). They attract::(MM)
……………..and…………and are
produced by activated…. cells
e.g ………../………..
(MNND) مندي neutrophils,monocytes, dendritic cells, and NK cells
8 & eotaxins
Monocytes& macrophages / T
RANTES & MCAF
Interleukin-12 (IL-12)
It is produced mainly by……………….and…………… cells.
• Principal mediator of early innate immune responses to…………. microbes.
• It is also a key inducer of…..
Stimulate the differentiation of ……to …..producing…..
Enhance cells cytolytic activity.
MQ& dendretic cells
Intracellular
CMI
TH0\IFNgamma/TH1
NK
Type I IFNs (virus infected cells)
IFN-α (leukocyte IFN): produced by……… phagocytes.
IFN-β (fibroblast IFN): produced by………….
Mononuclear
fibroblasts
Type I IFNs
Provides an early innate immune response against………….
Increases MHC class…… expression on
viral infected cells helping their recognition by………….. T lymphocytes (CTLs) to kill them.
Activates cells.
Viruses
II
Cytotoxic
NK
Cytokines that Regulate Adaptive Immune Responses
Produced primarily by… lymphocytes
They function in the proliferation and differentiation of……………….,………………
T
B lymphocytes and T lymphocytes
Th0»IL-2 /IL-4 /IFN-y→
Th1→ IL-…,…….,…….
Th2→ IL-… IL-… IL-…
IL-2 /INF gamma/TNF alpha&beta
IL-4 IL-6 IL-10
Interleukin-2 (IL-2)
IL-2 is produced mainly by….. lymphocytes and to a lesser extent….lymphocytes.
Action:
IL-2 is a growth factor+↑ the killing ability of…….
It stimulates antibody synthesis by… lymphocytes
Activates……./….. cell proliferation
CD4+ /CD8+
NK
B
macrophages
T
Type II Interferon (IFN-gam)
Produced by……. cells,…… cells and…. cells
It has…………… actions more than……….. actions.
Stimulates the differentiation of TH0 into……. cells and inhibits its differentiation into…. cells.
TH1/CD8/NK
immunoregulatory/antiviral
TH1/TH2
Stimulates B cells to produce…. subclasses /promote……… and mediates……
IgG
opsonization/ADCC
TNF-β
Produced by………………
locally acting cytokine and not a mediator of systemic complications.
TH1 lymphocytes.
IL-4
IL-4 is produced mainly by ……..cells and……. cells.
It stimulates the development of TH2 cells from TH0 and thus inhibits……….
…………..macrophage activation by IFNγ.
It stimulates the proliferation and differentiation of antigen-activated……. lymphocytes and the production of……(major production )&mast cell
TH2/mast
CMI
inhibits
B/IgE
IL-13 (same as IL-4)
Produced primarily by…… cells.
Increases the production of…….. by B lymphocytes.
Increases mucus production by lung epithelial cells and may play a role in……
TH2
IgE
asthma
IL-5
IL-5 is produced mainly by… cells.
IL-5 is a growth and activating factor for…………….. as a defense against helminths
TH2
eosinophils
TH-17 (IL-17, 21, 22)
{IL-17}
Stimulate phagocyte & mucosal epithelial cells→IL-…,IL-…&neutrophil-attracting chemokines
Neutrophils→——-
Macrophages→–…….
IL-1 IL-6
Chemokines
↑ Chemokines+ cytokine production
TH-17 (IL-17, 21, 22)
{IL-21}
Th-17 cell……….
B cells: isotype switching to all…. subclasses
Autocrine
Ig
TH-17 (IL-17, 21, 22)
{IL-22}
Stimulates mucosal epithelial cells → ↑production of
……………..,…………
Defensins
• Tight junction protein
Th-17 cytokines + recruited neutrophils=
Defend barrier tissues against bacterial & fungal infections
• Patients with IL-17 deficiency=
Mucocutaneous candidiasis
Cytokines that stimulate hematopoiesis
Stimulate the growth & differentiationof immature……..
1- stem cell factor made by ……. It makes the BM more responsive to ………/Promotes differentiation and survival of……..
leukocytes
bone marrow stromal cells
Various CSFs
stem cells
Cytokines that stimulate hematopoiesis
IL-7
Produced by ………
Acts on immature…………………….. and promotes expansion and maturation of T and B lymphocytes.
IL-3
Made by ………
IL-3 supports the growth of………………………………
bone marrow stromal cells.
lymphoid progenitors
T lymphocytes
multi- lineage bone marrow stem cells
Cytokines that stimulate hematopoiesis
Colony-stimulating factors (CSF)
Produced by …………………………..
It produces………,……..,……
Promotes growth and differentiation of…………. and…………… (neutrophils and macrophages).
الناس اللي عندهم ليكوبينا راح نعطيهم من الفاكتور حقت النخاع العظم
T cells, macrophages,endothelial cells and bone marrow stromal cells.
GM-CSF
G-CSF
M-CSF
granulocytes
myeloid cells
Inhibitory Cytokines
IL-10
Produced by ………….
Inhibit the production of……..+…..
Down regulate Both the……….immunity +specific …..
Inhibit MHC class…&…….
Th2 ,Treg ,MQ
IL-12 / IFN-g
Innate / cmir
II & antigen presenting cells
Inhibitory Cytokines
Transforming growth factor-beta TGF-B
Produced by……..
Inhibits the proliferation function of …&…………..+.. + ………
It also promotes …….production & ………
Treg MQ
T&B lymphocytes / NK /MQ
IgA /tissue repair