All properties of cytokinesis

1. CYTOKINES

2.  These are variety of regulatory or signaling molecules either small proteins or
glycoproteins produced by various nucleated cells in the body.
 As products of nucleated cells , they play a crucial role in the regulation of various
aspects of immunity including the intensity and duration of immune responses by immune
cells.
 They are pleiotropic hence have varying impacts on different types of cells . However ,
different types of cells also influence the activities of others and vice versa.
 Cytokines are also involved in the production and development of all the different types
of blood cells {Hematopoiesis}, angiogenesis and tumorigenesis.
 Cytokines can be classified as protein , peptides, and glycoproteins.
 They provide a signaling pathway that orchestrate the complex immune response of
human body.
 They are similar to hormones {Chemical messengers} but hormones have more variation
in molecule structure and are more involved in tissue signaling than cellular signaling.
 Each cytokine has a matching cell surface receptor {subsequent cascade } of
intracellular signaling then alter cell functions, i.e. ;Upregulation{increased expression}or
downregulation { decreased expression} of several genes and their transcription factors
resulting in the production of other cytokines . An increase in the number of certain
surface receptors for other molecules or suppression of their own effects by feedback
inhibition.

3. Basic functions and properties of cytokines
 1.}They are a group of low molecules weight regulatory proteins secreted by WBC
and other cells in the body.
 2.}There secretion is very specific and self limited because they are not usually stored
as preformed molecules. Cytokine synthesis is initiated by a new transcription as a
consequence of cellular activation . Once synthesized they are rapidly secreted
resulting in a burst of release when needed.
 3.}Once secreted cytokines regulate immune and inflammatory reactions.
 4.}Cytokines bind to specific receptors on the membrane of target cells , triggering
signal – transduction pathways that ultimately alter gene expression in the target
cells .
Nature of the target cell for a particular cytokine is determined by the presence
of
specific membrane receptors. Cytokines are specific due to their high affinity for
which Pico molar concentrations of cytokines can mediate a biological effect.

4.  5.}Cytokine actions may be local or systemic . Most of them act close to where they are
produced .
 Autocrine Action occurs when secreted cytokine binds to receptors on membrane of
the of same cells from where it is secreted .
 Paracrine Action occurs when a secreted cytokine binds to receptors on a target cell in
close proximity to the producer cell.
 Most cytokines acts on cells that are in contact with the cytokine producers but when
cytokine are produced in large amounts , it may enter the circulation and act at a
distance from the site of production- Endocrine Action.
 6.} Cytokines influence the synthesis and actions of other cytokines and different immune
cells .The ability of 1st
cytokine to stimulate production of others lead to cascade in
which a 2nd
or 3rd
cytokine may mediate the biological effects of the 1st
.
 Cytokines regulate the intensity and duration of the immune response by stimulating or
inhibiting the activation, proliferation and differentiation of various cells.
 7.} Cytokines secreted by a single lymphocyte following antigen –specific activation can
influence the activity of various cells involved in immune response. Eg ;Cytokines
produced by activated T-helper cels can influence the activity of B-cells , T cells , natural
killer cells , macrophages , granulocytes and hematopoietic stem cells .{It activates the
entire network of interacting cells .

5. Types of Cytokines
 These includes; 1. Interferons
2. Chemokines
3. Interleukins
4. Tumor Necrosis Factor.
 1. INTERLEUKINS
 They are glycoproteins involved in the activation and differentiation of immune cells.
 They also play a role in proliferation , migration, maturation, pro and anti-inflammatory activities
and adhesion of these cells.
 Together with there receptors , interleukins belong to a superfamily {IL Superfamily} made up of
proteins.
 Some interleukins are made up of proteins. This is in response to invading pathogens /antigens.
 While high volume can be produced depending on the type of interleukin and the invading
organism , a small quantity of the molecule is required to activate biological effects.
 Most of the Interleukins elicit an action on the same cell that produce them.

6.  Some interleukins can enter the blood stream allowing them to be transported and elicit
biological effect on distant cells in the body.ie; IL-2 elicit biological effect on T cells which
produced them. IL-1can enter the blood stream and reach the central nervous system.
 PROPERTIES OF INTERLEUKINS
 1. }Synthesis is a self limiting process
 2.}They stimulate up- regulatory and down-regulatory mechanisms
 3.}They have a redundant functions in the body . They can cause different effects on various
types of cells.
 4.}They can influence the synthesis and functioning of other interleukins
 FUNCTIONS OF DIFFERENT TYPES OF INTERLEUKINS
 1.} IL-1; Indirectly stimulate immune responses via various effector proteins and other
cytokines.
 2.} IL-2; Plays an important role in growth regulation of T cells.
 3.} IL-3; Stimulates the production of myeloid progenitor cells by hematopoietic stem cells.
An interaction IL-3 and IL-7 results in the production of lymphoid progenitor cells from
hematopoietic stem cells.
 4.} IL-4 ; Involved in a number of biological process ranging from the proliferation of T cells
and B cell stimulation to humoral and adaptive immunity.

7.  It continues to the production of a number of cells including dendritic cells as well as
Interferon gamma cells
 5.}IL-5 ; involved in stimulating the growth of B cells . It is also involved in increased
secretion of immunoglobin as well as eosinophils.
 6.}IL-6 ; Primary mediators of fever . Shown to overcome the blood-brain barrier in
activating the expression of prostaglandin E2 Iin the Hypothalamus which result in body
temperature change.
 7.}IL-8 ; Involved in the induction of chemotaxis.
 8.}IL-10; Involved in the inflammation and regulation of immune response.
 9.}IL-18; Involved in both immune response in the body {innate and adaptive responses}.
 10.}IL-33; Involved in immune response of the Th2 {Eg, Parasitic infections}.
INTERFERONS {IFNs}
 It is a family consisting of widely expressed signaling proteins.
 They are released by cells in the hosts immune system in response to invading organism
Eg;Bacteria and Viruses.
 They are also released to respond to tumorous cells in some organisms

8.  Types of Interferons include;
1. Type 1 IFNs
2. Type 11 IFNs
3. Type 111 IFNs
Type 1 IFNs
 They are divided into 2 major groups, ie; IFN- alpha and IFN –beta
 Additional Isotopes include IFN-k, IFN-omega
 IFN –alpha is further divided into several subtypes, ie IFN –alpha 1, IFN –alpha 2, IFN –
alpha 3, IFN –alpha 4, IFN- alpha 5 and IFN –alpha 6
 The production of type 1 IFN s is dependent on the presence of various
microorganism .ie, Following a viral infection, a signaling pathway that causes
phosphorylation and passage of interferon response factor 3{IRF3} to the nucleus is
activated.
 IRF3 with other transcription factors activates synthesis of IFN –beta gene that binds
to the interferon receptors located on the surface of an infected cell which
ultimately result in interferon response.
 Through these responses , interferons help in the recruitment of effector molecules
that protect the cells against infections .{Bacterial and viral infections}

9.  By activating the production of natural killer cells and macrophages , interferons
contribute to the destruction of viruses and infected cells.
 Cells responsible for the production of IFN-alpha and IFN –beta are known as
interferon –producing cells{IPCs} or natural interferon producing cells.
 Functions of the Type 1 interferon are divided into 3 main categories.
 1. Influence resistance to viral replication in cells- Achieved through destruction of
viral m RNA required for viral replication and inhibiting the translation of the viral
proteins.
 Promote ligand increase- Type 1 interferon promote increase in ligands to the
receptors of NK cells which in turn stimulates them to attack and lyse infected cells.
 Activate the destruction of infected cells by NK cells and macrophages.
 They are also used in treating Autoimmune diseases as they play a role in
immunosuppressive activities.
Type 11 Interferon
 It is made up of a single cytokine IFN-y , Which is largely produced by the THI T cells ,
activated by the Natural killer cels and CD8+ Tcells .
 The gene responsible for encoding the type 11 cytokine is located in the
chromosome 12 in human beings.

10.  IFN-y does not produce a potent antiviral effect . It largely servers to activate
effector cells.
 It is produced by T- cell in adaptive immunity {following an increase in antigen }and
produced by natural killer cells in innate immune system and acts as a mediator.
 In adaptive immunity, increased production of IFN-y is promoted by IL-12 and IL-18.
 IL-4 and IL-10 corresponds to negative regulators involved in its production.
 B cells and professional antigen –presenting cells also play a role in production of
IFN-y.
 IFN-y also contributes to cell response to viral infections.
 By activating and causing the induction of Major Histocompatibility Complex
{MHC},IFN-y plays a role in long term control of viral infections in cells .in this process ,
it also coordinates the transition from innate to adaptive immunity
 Some other functions include;
 1. Macrophage activation- IFN-y promotes the activation of macrophages
contributing to phagocytic and pinocytic activities of these cells hence contributes
to microbial destruction.
 2. Inhibiting cell growth- IFN-y inhibit cell growth promoting apoptosis.

11. Type 111 interferon
 They consist of a single cytokine
 They are divide into 3 cytokines .ie; IFN-lambda1, IFN-lambda 2, IFN-lambda3.
 They are also known as IL-28{ a and b} and IL-29
 They are characterized by a structure more similar to proteins of the family IL-10
 There signaling pathway resembles that of Type 1 interferon in that they are
dependent on the actions of IRFs and NF-KB
 They primarily function in mucosal epithelium cells and liver cells where they protect
them from viral infections.
2. Chemokines
 A type of protein cytokine that plays a role in chemotaxis.
 There are signals that guide certain immune cells to the affected sites.
 Currently identified chemokines are 50
 They are divided into 4 families based on the location of N-terminal cysteine
residues in there 3-dimensional structure.

12.  Tumor Necrosis Factor
 Consists of a group of proteins involved in a number of physiological and
pathological processes.
 40 members of the superfamily {TNF} have been identified with TNF –alpha and TNF –
beta being most notable ones
 TNF-alpha
 They are also known as TNF or TNFSF2
 A multifunctional cytokine involved in process such as apoptosis and coagulation.
 TNF –alpha genes are located on chromosome 6 . This allows the cytokine to be
expressed and produced by immune cells as macrophages , monocytes and T cells
in response to cytokines like IFN- gamma
 Characteristic of TNF- alpha include;
 1. It is synthesized as a 26-k D nonglycosylated type 11membrane protein.
 2. Types of TNF –alpha include m TNF –alpha and s TNF – alpha
 TNF –alpha is sometimes referred to as an adipostat due to adipose tissue expression.

13.  Functions of TNF – alpha
 1. Immune function- It attracts certain immune cells to the affected site by stimulating
the expression of adhesion molecules by vascular endothelial cells . This makes it
possible for immune cells to adhere to blood vessels walls and successfully migrate to
the infected site and destroy invading pathogens.
 2. Induces the production of chemokines that are involved in inflammatory responses-
they guide immune cells to the affected site.
 3. Apoptosis- They promote programmed cell death of tumor cells by promoting the
recruitment of proteins involved in death signaling.
 4. Biological functions- When produced in large amounts, they reduce blood pressure
or shock during severe infections . In some cases, high concentration of TNF- alpha
results in low blood sugar concentration and intravascular thrombosis.
 TNF –beta
 They are also known as lymhotoxin
 It is a type 2 transmembrane protein.
 Its expression is stimulated and activated by lymphocytes
 IT is a potent mediator involved in various immune and inflammatory responses.

14.  Its involved in;
1.Apoptois
2.Coagulation
3.Cell proliferation and differentiation

18. Clinical Correllates
 Autoimmune Disease.
- In rheumatoid arthritis and systemic lupus erythematosus, elevated levels of cytokines like TNF-a, IL-17A,IL-1B,
and IFN-Y indicate chronic inflammation.
- IL-4 and IL-10 are linked to lupus nephritis, suggesting B-cell involvement.
- Cytokine profiling helps differentiate between RA and SLE and guides targeted therapies.
 Neurodegenerative Disorders.
-In multiple system atrophy, TNF-a and IL-6 levels corelate with anxiety and depression symptoms, and TNF-a shows
diagnostic potential.
- These cytokines may serve as biomarkers for disease progression and therapeutic response
 Diagnostic and Prognostic Value. Cytokine levels in blood can be used to;
- Diagnose autoimmune and inflammatory diseases,
- Monitor disease activity and treatment response,
- Predict complications like cardiovascular risk eg TNF-a and CX3CL1 negatively correlate with HDL LEVELS IN RA
and SLE
 Therapeutic Targets.
- Drug targeting cytokines eg anti-TNF agents like infliximab are used to treat RA, Crohn’s disease and psoriasis.
- CX3CL1 is emerging as a potential therapeutic target in RA