Cytokines - Introduction Flashcards

1
Q

What are the six functions of cytokines?

A

Development of cellular and humoral responses

Induction of inflammatroy responses

Regulation of haematopoiesis

Cellular proliferation and differentiation

Growth inhibition and apoptosis

Wound healing

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2
Q

Give an example of a cytokine involved in the development of cellular and humoral responses

A

Interferon gamma activates macrophages

Interferon gamma can help mobilise macrophages

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3
Q

Give an example of a cytokine involved in the induction of inflammatory resopnses

A

IL4 or IL5 can help B cells activate

IL1, IL6 and TNFalpha cause local changes to blood vessels, local responses to infection, increase in liver acute phase proteins, bone marrow haematopoeisis etc

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4
Q

Give an example of a cytokine involved in the regulation of haematopoiesis

A

G-CSF

Responsible for telling the bone marrow that we need more neutrophils

It send stem cells in the bone marrow down the neutrophil pathway

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5
Q

Give an example of a cytokine involved in cellular proliferation and differentiation

A

IL2 for T cell proliferation

Interferon gamma for monocyte differentiation into macrophages

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6
Q

Give an example of a cytokine involved in growth inhibition and apoptosis

A

TNF alpha = tumour necrosis factor which has the ability to bring about apoptosis in some tumour cells

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7
Q

Give an example of a cytokine involved in wound healing

A

TGF beta

Involved in the resolution of inflammation and eventually wound healing

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8
Q

Why did cytokine study not really progress until the 1970s?

A

Cytokines are ephemeral small labile molecules i.e. they are produced in very small amounts and they are broken down quickly if they dont bind to their receptor -> theyre there then theyre gone

Until PCR studies and cloning techniques used to make huge amounts of these proteins they were very difficult to study

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9
Q

Give a quick run down on the history of the discovery of cytokeins

A

In 1944 Menkin purified a “fever inducing” compound from pus and called it “pyrexin” -> he injected this into animals and noticed it induced a fever but it wasnt pure -> contained bacteria etc

In 1953 Bennet and Beeson purified an endogenous pyrogen from a persons leukocytes which they called endogenous pyrogen but later became known as IL-1 when we found more endogenous pyrogens

In 1957 Isaacs and Lindenmann identified interferons

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10
Q

Who discovered interferons, when did they and why was this significant?

A

Isaacs and Lindenmann discovered them in 1957

This was a huge deal as they noted the interferons ability to interere with viral replication

It was thought that a purified interferon would solve any viral disease however this was not the case

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11
Q

Who discovered interferons, when did they and why was this significant?

A

Isaacs and Lindenmann discovered them in 1957

This was a huge deal as they noted the interferons ability to interere with viral replication

It was thought that a purified interferon would solve any viral disease however this was not the case

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12
Q

What are cytokines?

A

Low molecular weight glycoproteins of <30kDa

They are messengers that are secreted by a producer cell and have their effects on a target cell

They are soluble proteins secreted by one cell of the immune system and have an effect on another cell

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13
Q

How is a cytokine different from a hormone?

A

Hormones are generally produced by glands such as the pancrease while cytokines are produced by individual cells

Different cells can produce the same cytokine unlike hormones e.g. where only B cells of the pancreas can prodce insulin

Cytokines are essentially messengers of the immune system while hormones are messengers of the endorcrine system

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14
Q

What does cytokine mean, howd it get its name?

A

Cell kinesis i.e. this molecule causes cells to move towards it -> this was what was originaly thought

When first named they were probably looking at a chemokine hence the name

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15
Q

What are the five main families of cytokines?

A

Interleukins
Chemokines
Interferons
Colony stimulating factors
Tumour necrosis factors

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16
Q

What are interleukins, howd they get there name?

A

These were cytokines initially thought to be expressed only be leucocytes
We now know other cells produce these

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17
Q

What are chemokines, howd they get their name?

A

Cytokines whicha re chemotactic i.e. make cells move

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18
Q

What are interferons, howd they get their name?

A

Involved in defence against viruses

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19
Q

What are the different kinds of interferons?

A

Type 1: alpha and beta interferons
- these are very antiviral

Type 2: interferon gamma
- has other effects such as macrophage

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20
Q

What are colony stimulating factors?

A

These promote cell production and differentiation
e.g. G-CSF and GM-CSF

21
Q

What are tumour necrosis factors?

A

Cytokines that promote inflammation and can cause cell death of tumour cells e.g. TNFa and TNFB

22
Q

What are the properies of cytokines?

A

They bnd to specific receptors on target cells to initiate signal transduction cascades resulting in altered gene expression in the target cell

Cytokines are generally labile

23
Q

Talk about the relationship between a cytokine and its receptor in gene regulation

A

regulation of gene expression is controlled by both the amount of cytokine produced as well as the degree of expression of the receptor on the target cell

Cytokines are their receptors are highly specific and therefore bind with high affinity

This means very low amounts of the cytokine are actually needed to exert their effects -> i.e. high sensitivity

Because of this cytokines are generall very labile and tend to be metabolised quickly if they do not bind to their receptor so as to prevent unwanted chemokine action

24
Q

What concentrations are cytokines found in in the body?

A

Picomolar concentrations

25
Q

What are the three ways a cytokine can exert their effects?

A

Autocrine fashion
Paracrine fashion
Endocrine fashion

26
Q

What is meant by the autocrine function of a cytokine, give an example?

A

Whereby the producer cell is affected by its own cytokine production

e.g. T cell production of IL2
-> When activated the T cell produces IL2 which brings about T cell proliferation

27
Q

What is meant by the paracrine function of a cytokine, give an example?

A

Whereby the neighbouring cell is affected by the production of a cytokine

e.g. between an APC and a T cell

28
Q

What is meant by the endocrine function of a cytokine, give two examples?

A

This is where the cytokines effects are systematic or affect distant organs/cells

e.g. macrophage production of IL-1 which affects hypothalmus of the brain to bring about an increase in temperature through prostaglandins

e.g. G-CSF produced in inflammed tissue -> affects the bone marrow to bring about production of more neutrophils

29
Q

What is meant by the endocrine function of a cytokine, give two examples?

A

This is where the cytokines effects are systematic or affect distant organs/cells

e.g. macrophage production of IL-1 which affects hypothalmus of the brain to bring about an increase in temperature through prostaglandins

e.g. G-CSF produced in inflammed tissue -> affects the bone marrow to bring about production of more neutrophils

30
Q

In general what are the four effects a cytokine can have?

A

Pleiotrophy
Synergy
Antagonism
Cascade induction

31
Q

What is the pleiotrophy property of cytokines, give an example?

A

Whereby one cytokin can have several different effects depending on the context

e.g. IL4 can bring about proliferation of B cells, thymocytes and mast cells but it can also bring about B cell proliferation and differentiation

32
Q

What is the redundancy property of cytokines, give an example?

A

This is where different cytokines can have the same effects

e.g. IL-2, IL-4 and IL-5 can all bring about B cell proliferation -> in each context one of these might be more important etc etc

33
Q

What is the synergy property of cytokines, give an example?

A

Cytokines can work together to producce a different outcome than on their own -> ie. combined effect is different from singular effect

The combination of IL4 and IL5 brings about class switching to IgE -> wont get IgE with IL4 or IL5 on their own

34
Q

What is the antagonism property of cytokines, give an example?

A

The effect of one cytokines inhibits/offsets the activity of another

e.g. IL-4 brings bout B cell proliferation, IFN-y inhibits this

35
Q

What is the cascade induction property of cytokines, give an example?

A

This is where one cytokine can drive the production of another

e.g. IFN-y produced by activated T-helper cells -> IFN-y acts on macrophages -> IL-12 produced -> IL-12 acts on T-helper cell -> More IFN-y produced as well as TNF, IL-2 and other cytokines

36
Q

What cells produce cytokines?

A

It was thought that only lymphocytes and monocytes produce cytokines

We now know T helper cells and macrophages are the most potent producers of cytokines but than epithelial and endothelial cells are also capable of cytokine production

37
Q

Give some examples of haematopoietic cytokines

A

GM-CSF -> Granulocyte/monocyte colony stimulating factor -> induces neutrophil or monocyte production in granulocte-monocyte progenitors

IL-7, IL-5 and IL3 all have roles in producing different wbcs as well

38
Q

What are the three main acute phase activating cytokines and what are they produced by?

A

IL-1
IL-6
TNF-alpha

These are produced by macrophages

39
Q

What are the main functions of the acute phase cytokines

A

They act on the hypothalamus to induce prostaglandins to cause fever

They act on the liver to increase acute phase proteins such as CRP

They act on the bone marrow to bring about leucocytosis

40
Q

Why is CRP considered a good acute phase protein?

A

CRP is a downstream molecule from the production/work of acute phase cytokines TNFa, IL1 and IL6

41
Q

How do interferons work?

A

They have a paracrine response i.e. they are produced by a virally infected cell and affect any neighbouring healthy cells

42
Q

How does interferon affect a cell?

A

Activates RNase enzymes
Increases MHC class I expression
Activation of dendritic cells and natural killer cells
Downregulation of protein translation -> this means that if the cell does become infected then the virus cannot produce its own proteins
Stimulation of Th1 responses (T-helper)

In general: interferons induce changes that protect the cell such as stimulating genes for antiviral proteins which block viral reproduction

43
Q

How does interferon affect a cell?

A

Activates RNase enzymes
Increases MHC class I expression
Activation of dendritic cells and natural killer cells
Downregulation of protein translation -> this means that if the cell does become infected then the virus cannot produce its own proteins
Stimulation of Th1 responses (T-helper)

In general: interferons induce changes that protect the cell such as stimulating genes for antiviral proteins which block viral reproduction

44
Q

What are chemokines, how do they work, how are they classified?

A

They are a family of small (8-10kDa) protein cytokines (chemotactic cytokines)

Cells move in the direction of increasing chemokine concentration

They are classified based upon the relative spacing and sequence of cystine residues e.g. CC, CXC, CX3C chemokines etc etc

CCL1 is ligand 1 of the CC family and CCR1 is the receptor of the family

45
Q

Talk about the regulation of cytokine receptor expression

A

The expression of a particular cytokine receptor dictates whether a cytokine will affect the cell or not

i.e. if a receptor is not expressed by a cell then the cell will not care about cytokines produced

The expression of cytokine receptors is tightly regulated and varies depending upon circumsances

Because of the high affinity of cytokines and their potent activity, cytokine receptors are expressed at relatively low levels

46
Q

Talk about the regulation of cytokine receptor expression

A

The expression of a particular cytokine receptor dictates whether a cytokine will affect the cell or not

i.e. if a receptor is not expressed by a cell then the cell will not care about cytokines produced

The expression of cytokine receptors is tightly regulated and varies depending upon circumsances

Because of the high affinity of cytokines and their potent activity, cytokine receptors are expressed at relatively low levels

47
Q

What are the five types of cytokine receptors?

A

Immunoglobulin superfamily receptors e.g. IL-1

Class I cytokine receptors (haematopoietin) e.g. IL-2/3/4/5/6/7 etc

Class II cytokine receptors (interferon) e.g. IFN-alpha/beta/gamma

TNF receptors e.g. TNF alpha/beta

Chemokine receptors e.g. IL-8

48
Q

What are chemokine receptors such as IL-8?

A

These span the membrane 7 times

They are G-protein associated

49
Q

What is similar about both the structures of class I and class II cytokine receptors?

A

They are both dimeric receptors