Week 4 Lec: Cytokines Flashcards
These are small soluble proteins that regulate the immune system, orchestrating both innate immunity and the adaptive response to infection.
Cytokines
These are chemical messengers involved in the regulation of other activities of the cell, and are so called signaling polypeptides.
Cytokines
Cytokines are induced in response to?
specific stimuli
Examples of specific stimuli.
- bacterial lipopolysaccharides
- flagellin
- other bacterial products
Cytokines are induced in response to specific stimuli through?
the ligation of cell adhesion molecules or through the recognition of foreign antigens by host lymphocytes
The effects of cytokines in vivo include?
- regulation of growth
- differentiation
- gene expression by many different cell types, including leukocytes
True or false: Individual cytokines do not act alone but in conjunction with many other cytokines that are induced during the process of immune activation.
True
The resulting network of cytokine expression regulates __________ and leads to the ___________________.
leukocyte activity; elimination of the infection
It means having many different effects.
pleiotropic
The pleiotropic (i.e., having many different effects) nature of cytokine activity relates to the widespread distribution of cytokine receptors on many cell types and the ability of cytokines to _____________________.
alter expression of numerous genes
This feature of cytokines means that they share the same receptor.
Redundancy
Massive uncontrolled overproduction and dysregulation of cytokines may lead to?
- Shock
- Multi-organ failure
- Death
Event in which a cytokine fights another cytokine to stop its production.
Antagonistic effect
Event wherein various inflammatory cytokines are produced at a much higher rate than normal (overproduction and dysregulation of the cytokines)?
cytokine storm
Actions of cytokines affecting the same cell that secreted it.
Autocrine
Actions of cytokines affecting a target cell in close proximity.
Paracrine
Actions of cytokines wherein occasionally, they will also exert systemic activities.
Endocrine
single cytokine has many different actions
Pleiotropism
different cytokines often have very similar effects
Redundancy
cooperative effect of multiple cytokines
Synergy
inhibition of one cytokine effects by another cytokine
Antagonist
stimulate the release of other cytokines
Act in networks
modulate the number and composition of cells
Act as growth factors for hematopoietic cells
Different Types/Families Cytokines?
- Tumor Necrosis factors (TNF)
- Interferons (IFN)
- Chemokines
- Transforming Growth Factors (TGF)
- Colony Stimulating factors (CSF)
- Interleukins (IL)
Cytokines involved in the _______________ are responsible for many of the physical symptoms attributed to inflammation, such as fever, swelling, pain, and cellular infiltrates into damaged tissues.
innate immune response
Inflammatory agents involved in the innate immune response?
IL-1, IL-6, IL-8 and TNF-α
The main function of the innate immune response is to?
recruit effector cells to the area
Cytokines involved in the innate immune response?
- interleukin-1
- tumor necrosis factor-alpha
- interleukin-6
- chemokines
- transforming growth factor-beta
- interferons-alpha and beta
Mediator of the innate immune response.
IL-1
Types of IL-1?
- IL-1α
- IL-1β
- IL-1RA (IL-1 Receptor antagonist)
Pro-inflammatory cytokines produce by monocytes and macrophage?
- IL-1α
- IL-1β
It is also produced by monocytes and macrophages. It acts as an antagonist to IL-1 by blocking the IL-1 receptor and limiting the availability of the receptor for IL-1.
IL-1RA (IL-1 Receptor antagonist)
This helps to regulate the physiological response to IL-1 and turn off the response when no longer needed.
IL-1RA (IL-1 Receptor antagonist)
Principal mediator of the acute inflammatory response to gram-negative bacteria and other infectious microbes.
Tumor Necrosis Factor
It stimulates gene transcription or induces apoptosis.
Tumor Necrosis Factor
Tumor Necrosis Factor stimulates _________ or induces __________.
stimulates gene transcription or induces apoptosis
They were first isolated from tumor cells and were so named because they induced lysis in these cells.
TNF-α
The most prominent member of the TNF family.
TNF-α
TNF-α exists in both _____ and _____ forms.
membrane-bound and soluble forms
They exist in both membrane-bound and soluble forms.
TNF-α
TNF-α causes?
vasodilation and increased vasopermeability
They cause vasodilation and increased vasopermeability.
TNF-α
It is secreted by activated monocytes and macrophage.
TNF-α
TNF-α is secreted by?
activated monocytes and macrophage
It is a single protein produced by both lymphoid and nonlymphoid cell types.
IL-6
It is part of the cytokine cascade released in response to lipopolysaccharide.
IL-6
IL-6 is part of the cytokine cascade released in response to?
lipopolysaccharide
It plays an important role in acute phase reactions and the adaptive immune response.
IL-6
IL-6 is expressed by a variety of normal and transformed cells, including?
T cells, B cells, monocytes and macrophages, fibroblasts, hepatocytes, keratinocytes, astrocytes, vascular endothelial cells, and various tumor cells
IL-1 primarily triggers its secretion
IL-6
Which interleukin tiggers the secretion of IL-6?
IL-1
Pleomorphic Activities of IL-6?
- Inflammation
- Acute phase reactions
- Immunoglobulins synthesis
- Activation states of B cells and T cells
- Proliferation and differentiation of B cells into Plasma cells
They are a family of cytokines that enhance motility and promote migration of many types of white blood cells toward the source of this cytokine.
Chemokine
The chemokines are classified into four families based on the?
position of N-terminal cysteine residues
Four families based on the position of N-terminal cysteine residues?
- Alpha, or CXC, chemokine
- Beta or CC, chemokines
- C chemokines
- CX3C
Family of cytokine that contains a single amino acid between the first and second cysteines.
Alpha, or CXC, chemokine
Family of cytokine that has adjacent cysteine residues.
Beta or CC, chemokines
Family of cytokine that lacks one of the cysteines.
C chemokines
Family of cytokine that has three amino acids between the cysteines.
CX3C
It was originally characterized as a factor that induced growth arrest in tumor cells.
TGF- β
TGF- β was originally characterized as a?
factor that induced growth arrest in tumor cells
Later, TGF- β was identified as a factor that induces?
antiproliferative activity in a wide variety of cell types
Were originally named because they literally interfere with viral replication process in an infected cell.
IFN-α and IFN-β
Cytokines for immunoregulation?
IFN-α and IFN-β
Type 1 IFN is also called?
non-immune IFN
Why is Type 1 IFN also called non-immune IFN?
because they are produced primarily during initial innate response to viral infection
Interferon primarily produced by mononuclear phagocytes.
IFN-α
IFN-α is primarily produced by?
mononuclear phagocytes
Interferon primarily produced by Fibroblast?
IFN-β
IFN-β is primarily produced by?
Fibroblast
It is also called leukocyte interferon.
IFN-α
It is also called fibroblast interferon.
IFN-β
Adaptive immune response are mainly secreted by ________ and affect T- and B-cell function more directly.
T cells, especially T helper (Th) cells
Subclasses of T-helper cells?
- Th1
- Th2
- T-reg
Th1 cytokines?
IL-2, IFN-γ
Th2 cytokines?
IL-4, IL-5, IL-10
It regulates the activity of Th1 and Th2.
T-regulatory cells
Dendritic cells in damaged tissues produce _____ in response to certain stimuli such as mycobacteria, intracellular bacteria, and viruses.
IL-12
Dendritic cells capture antigen through?
phagocytosis and endocytosis
Th1 cytokines are produced by?
macrophages and B cells
Th1 cytokines have multiple effects on both?
T cells and natural killer (NK) cells
This binds to its receptor on naïve T cells and causes the expression of a new set of genes, including those that determine maturation into the Th1 lineage.
IL-12
Activation of Th1 cells induces high-level expression of?
IFN-ɣ
These are produced mainly by Th1 cells.
IFN-ɣ
IFN-ɣ stimulates?
antigen presentation by Class II MHC molecules
This regulates all genes involved in the regulation and activation of CD4+ Th1 cells, CD8+ cytotoxic lymphocytes, NK cells, bactericidal activities, IL-12R and IL-18R.
IFN-ɣ
IFN-ɣ production can be stimulated in mature Th1 cells by two means?
(1) ligation of the T-cell receptor (TCR) by MHC-peptide antigen presentation
(2) cytokine stimulation by IL-12 and IL-18
They act synergistically to stimulate IFN-ɣ production.
IL-12 and IL-18
Also secreted by Th1 cells and known as the T-cell growth factor.
IL-2
It drives the growth and differentiation of both T and B cells and induces lytic activity in NK cells.
IL-2
IL-2 acts in synergy with ___ to promote growth of T-cytotoxic cells.
IL-12
Th2 Cytokines?
- IL-4
- IL-5
- IL-10
It triggers activation, proliferation and differentiation of B-cells and also induces T-cell proliferation.
IL-4
It is responsible in allergic reactions, parasitic infections and autoimmune diseases.
IL-4
IL-4 increases expression of ____ on resting B cells.
MHC-II
Inhibits production of pro-inflammatory cytokines by mononuclear phagocytes.
IL-10
Inhibits the accessory functions of mononuclear phagocytes for T-cell activation.
IL-10
It acts an antagonist to IFN- ɣ.
IL-10
IL-10 acts an antagonist to?
IFN- ɣ
Erythropoietin and Colony Stimulating Factors?
- IL-3
- EPO: Erythropoietin
- TPO: Thrombopoietin
- G-CSF: Granulocyte- colony stimulating factor
- M-CSF: Megkaryocyte- colony stimulating factor
- GM-CSF: Granulocyte-macrophage-colony stimulating factor
A hormone residing in the kidneys that regulates RBC production. It is given to people with low hemoglobin, platelet, hemtocrit, and RBC.
EPO: Erythropoietin
Normal serum values of EPO?
5-28 units/L
A hormone for platelet production that resides in the liver.
TPO: Thrombopoietin
CSF that becomes neutrophil and enhances the function of mature cells.
G-CSF: Granulocyte-colony stimulating factor
CSF involved in platelet production and increases during phagocytosis and chemotaxis.
M-CSF: Megkaryocyte-colony stimulating factor
CSF involved during differentiation towards other WBC types.
GM-CSF: Granulocyte-macrophage-colony stimulating factor
