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3rd Year Biomed > Immunology (Liz - Cytokines) > Flashcards

Immunology (Liz - Cytokines) Flashcards

1
Q

What is a cytokine and what is its action?

A
  • A group of low molecular weight regulatory proteins
  • Secreted mainly by immune cells in response to a signal
  • Bind to specific receptors, resulting in signal transduction and alter gene expression
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2
Q

What is pleiotrophy?

A

When a single cytokine has different effects on different cell types

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3
Q

What is redundancy?

A

When different cytokines have the same effect on a target cell

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4
Q

What is synergy?

A

When combinations of cytokines together have a stimulatory effect

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5
Q

What is antagonism?

A

When combinations of cytokines together have inhibitory effect

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6
Q

To clarify how cytokines differ from endocrine hormones, explain each in terms of their:

  • site of production
  • cellular targets
  • biological role
  • redundancy
  • pleiotrophy
  • sphere of incluence
  • inducing stimulus
A

Hormones:

  • Few
  • Many
  • Homeostasis
  • Low
  • Low
  • Widespread
  • Physiological change

Cytokines:

  • Many
  • Few
  • Fighting infection
  • High
  • High
  • Local
  • Infection, tissue damage
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7
Q

Describe the general crystal structure of cytokines

A
  • 4 alpha-helical regions (A-D) in which the A/B and C/d pairings run roughly parallel to each other in alternating directions
  • Little or no beta-sheet structure
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8
Q

What are the approx size of cytokines?

A

25 kDa

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9
Q

Cytokines are grouped into families based on what?

A

Structure

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10
Q

How many members are there of the IL-1 family and what is their role? Give examples

A

IL-1 family has 11 members
e.g IL-1alpha, IL-1beta IL-18 and IL-33
Role: inflammatory mediators

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11
Q

What non immune and immune proteins are in the haematopoeitin family (Class I cytokine family)?

A

Non immune proteins e.g. erythropoetin and growth hormone

Immune cytokines e.g IL-2,3,4,5&6 and GM-CSF

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12
Q

What cytokines are in the interferon (class II) family?

A 
IFN-alpha
IFN-beta
IFN-gamma
IL-10
IL-19
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13
Q

What is the role of class II cytokines?

A

Mainly antiviral in action

Some control immune responses

E.g. IFN-gamma upregulates MHC class II expression

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14
Q

What are included in the TNF family? What are their roles?

A

More than 17 cytokines including TNF-alpha and TNF-beta

Many functions in immune cell development and function

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15
Q

Give some examples of the general roles of cytokines

A

1) Up or down-regulate enzyme activity in target cell
2) Change level of transcription of particular genes in a receptor bearing cell
3) Can instruct cell survival or death

‘Immune cell messangers’

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16
Q

What is a chemokine and what is its role?

A
  • A sub class of cytokine
  • Lower molecular weight than a cytokine
  • Causes chemotaxis (movement of pre-activated WBC) from one area to another
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17
Q

How do leukocytes move to infected tissue and at what speed?

A

Move up a chemokine concentration gradient towards infected tissue

Can move up to 30µm/min

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18
Q

Do immune cells always have chemokine and cytokine receptors?

A

No, only when they’re activated by an antigen do they express the receptors

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19
Q

What are the properties of cytokines?

A
  • Work by binding to membrane receptors on target cells
  • Bind with high affinity
  • Extremely low concentrations of cytokine are able to mediate its effect (picomolar = 10^-12 M)
  • Very similar or identical functions
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20
Q

Cytokines secreted by a single Th cell following antigen specific activation can influence the activity of what cell types?

A
  • B cells
  • Cytotoxic T cells
  • NK cells
  • Macrophages
  • Granulocytes
  • Haematopoietic stem cells
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21
Q

What 5 cytokines/chemokines are produced by macrophages in response to an infection? What do all of the effects have in common?

A 
IL-1beta
TNF-alpha
IL-6
CXCL8 
IL-12

All have pro-inflammatory effects

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22
Q

Differentiation of CD4+ Th cells into Th1 or Th2 cells depends on what?

A

The type of pathogen they encounter

23
Q

CD4+ Th cells that encounter bacteria or viruses usually become what and why?

A

Th1 cells

Because these pathogens cause DCs to produce IL-12 and NK cells to produce IFN-gamma

Causes differentiation to Th1 cells

24
Q

CD4+ Th cells that encounter worms and some other pathogens usually become what and why?

A

Th2 cells

Worms cause NK cells to secrete IL-4

Causes differentiation to Th2 cells

25
Q

What are the main functions of Th1 and Th2 cells?

A

Th1: Helping cells which are fighting intracellular viral infections e.g. cytotoxic T cells

Th2: helping cells fighting bacteria, protozoa, fungi and parasites e.g. B cells (via antibodies), eosinophils and mast cells

26
Q

What is linked recognition?

A

A B cell can only be activated by a Th2 cell that responds to the same antigen

27
Q

How does a Th2 cell cause a B cell to become a plasma cell?

A

Production of the cytokines IL-4, IL-5 and IL-6 which cause proliferation and differentiation into plasma cells

28
Q

Describe the interaction between a Th cell and a B cell

A

1) T cell receptor binds to MHC and CD4 on B cell
2) This induces the CD40 ligand on the T cell which binds to CD40 on the B cell
3) The integrin LFA-1 on the T cell binds to the adhesion molecule ICAM-1 on the B cell
4) The cytoskeletal protein talin becomes relocated to the point of cell/cell contact
5) The golgi also becomes re-orientated by the cytoskeleton to the point of B cell contact
6) Cytokines e.g IL-4 are released at the point of contact

29
Q

Cytokines play an essential role in what generative process?

A

Generation of all blood cells from the bone marrrow

30
Q

Give some examples of cytokines involved in blood cell production

A

1) SCF - stem cell factor
2) GM-CSF - granulocyte-macrophage colony-stimulating factor
3) G-CSF - Granulocyte-colony stimulating factor
4) M-CSF - Macrophage-colony stimulating factor

31
Q

What is the structure of the moderate affinity and high affinity IL-2 receptor?

A

Moderate:

  • only the beta and gamma chain
  • requires very high concentrations of IL-2

High:

  • beta, gamma and alpha chain
  • only needs very low concentrations of IL-2
32
Q

When do both receptor types exist?

A

Resting (i.e naive) T cells and NK cells express the moderate affinity receptor

One activated, T cells produce about 50,000 low affinity (alpha chain only) receptors and 5,000 high affinity

33
Q

After activation, what are T cells able to do?

A

Secrete IL-2

  • Binds to its own receptors on the T cell
  • Induces proliferation
34
Q

What is the common gamma chain (gamma-c)?

A

A component of many vital cytokine receptors

35
Q

What occurs if the common gamma chain is missing is certain cytokine receptors?

A
  • The receptor cannot bind the intracellular JAK 3 tyrosine kinase domain
  • No signal transduction (STAT signalling) to nuclues
  • No transcription therefore no cytokine effect
36
Q

Individuals born with no common gamma chain have what disease?

A

X-linked severe combined immunodeficiency disease

37
Q

How do some APCs recognise virally produced dsRNA or ssRNA?

A

ssRNA recognised by TLR-7 and dsRNA recognised by TLR-3

  • Found on endosomes
  • Viral RNA binds to these TLRs after viral uptake and processing via the endosomic pathway
38
Q

What occurs in the cell when viral DNA binds to TLRs?

A
  • Induced production of type 1 interferons (alpha and beta)

- Membrane protein UNC93B essential for signalling via these receptors

39
Q

Describe the signalling pathway from TLR-3

A
  • First, membrane protein UNC93B
  • TLR-3 signalling dependant on a pathway of the adaptor TRIF and primarily activates interferon-regulatory factors IRF3 and IRF7
40
Q

Describe the signalling pathway from TLR-7

A
  • First, membrane protein UNC93B
  • TLR-7 signals through a pathway dependant on the adaptor MyD88 that involves IRAKs and primarily activates the classical NFkB pathway
41
Q

What happens to the produced IFN-a/B?

A
  • Secreted by DCs
  • Bind to alpha and beta interferon receptors on neigbouring cells
  • Binding activates kinases JAK1 and TYK2
  • These activate transcription factor ISGF3
  • This drives expression of type I IFN-dependant genes in the nucleus
  • These genes encode proteins that mediate antiviral response
42
Q

What anti-viral genes are turned on by IFN alpha and beta?

A

1) Protein kinase R (PKR) - binds to dsRNA, inhibiting its translation
2) 2,5, oligo A synthetase - leads to mRNA degradation
3) Mx protein - inhibit viral replication

43
Q

What are the 3 main roles of IFN alpha and beta? (summary)

A

1) Induce resistance to viral replication in uninfected cells by activating genes that cause mRNA destruction and inhibit translation of viral proteins
2) May increase sysnthesis of MHC class I in viral infected cells, making them more susceptible to killing by cytotoxic T cells
3) Activate NK cells, which are capable of selectively killing virus infected cells

44
Q

Name 4 examples of diseases caused by altered cytokine secretion or altered cytokine receptor subunit expression?

A

1) Bacterial superantigens (septic shock)
2) X-linked SCID
3) Chagas’ disease
4) Lymphoid and myeloid cancers

45
Q

How do bacterial superantigens cause septic shock?

A
  • Bind to the outside of T cell receptors, causing non specific T cell activation
  • Causes huge release of cytokines such as TNF-alpha and IL-1beta
46
Q

Give an example of a bacterial superantigen

A

TSST-1 toxin produced by staphylococcus aureus

47
Q

What is Chagas’ disease?

A

The protozoan Trypanosome worm (T.cruzi) causes a drastic reduction in the expression of the IL-2R alpha subunit needed to produce the high affinity IL-2 receptor

48
Q

What is X-linked SCID?

A

Mutation in the common gamma chain subunit of IL-2 and other cytokine receptors
- No T and B cell activation via IL-2/IL2R interaction

49
Q

What is the most common way to reverse primary immunodeficiencies?

A

Bone marrow transplants

50
Q

What is a problem with bone marrow transplants?

A

Rejection

  • Mature T cells that contaminate the bone marrow graft attack host cells causing graft versus human disease (GvHD)
51
Q

Describe how lymphoid and myeloid cancers may occur from altered cytokine expression

A

Infection with HTLV-1 virus (Human T-lymphotropic virus) causes constitutive high expression of IL-2 and IL-2R

  • Results in uncontrolled proliferation of the leukocyte-derived cancers cells
  • Leads to development of adult leukemia and lymphoma diseases
52
Q

Name some ways in which viruses can mediate immune mechanisms to evade cytokines

A

1) Interfere with cytokine production
2) Produce copies of cytokines the body normally uses to stop anti-viral response e.g. IL-10
3) Produce soluble cytokine receptors
4) Interfere with the action of interferon alpha and beta

53
Q

Summary of the roles of cytokines (no question, just read)

A
  • Cytokines act as intercellular messengers that evoke particular biological activities after binding to a receptor on a responsive target cell.
  • Helper T cells and macrophages produce the most cytokines, although many other cell types are also capable of producing them.
  • The physiological responses that cytokines control are:
    The Inflammatory response to infection
  • The proliferation, differentiation and control of both innate (e.g. macrophage, NK cell) and adaptive (B and T lymphocyte) immune cells (survival or death!).
  • Haematopoiesis (the formation of new blood cells)
  • The induction of wound healing.

3rd Year Biomed (44 decks)

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