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FunMed Immunology > Cytokines > Flashcards

Cytokines Flashcards

1
Q

what are cytokiens

A
  • A group of small proteins and glycoproteins made by immune cells that act as chemical messengers.
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2
Q

What is the overall function of a cytokine

A
  • Regulate the immune response

- Affect cell behaviour by binding to cell receptors and causing a biological effect

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3
Q

What does the immune system require

A
  • the immune system requires efficient communication between its constituent parts, it involves mechanisms that rely on cell contact and soluble cytokines that signal between cells
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4
Q

What is the structure of cytokines

A
  • Small proteins or glycoproteins
  • Act via specific receptors
  • Influence innate immunity, adaptive immunity and haematopoiesis
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5
Q

Name some examples of cytokines

A
  • Interleukins
  • Interferons such as IFN gamma
  • Some are called interleukins -IL1 to IL37
  • Tumour Necrosis Factor (TNF-alpha)
  • Lymphokines
  • Chemokines – induce directed chemotaxis
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6
Q

What are chemotaxis

A
  • This is the movement of an organism in response to chemical stimulus
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7
Q

what is directed chemotaxis

A
  • Directed chemotaxis is the movement of an organism in response to a chemical stimulus
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8
Q

what are the attributes of cytokines

A

Pleiotropy: a cytokine can have multiple effects
Redundancy: different cytokines can do the same job
Synergy: cytokines act together to cause an effect
Antagonism: cytokines can also have opposing effect

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9
Q

describe how directed chemotaxis work

A
  • Migration along chemokine concentration gradients provides directional movement
  • Cell produces chemokine, chemokines move away down concentration gradient, chemokine receptor cell senses the concentration gradient and moves along it
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10
Q

what is the structure of chemokine

A
  • Small polypeptides (90-130aa)
  • Signal through G protein coupled receptors (GPCRs) as this is what they bind to
  • Receptors can bind multiple chemokines
  • Different leukocytes express different chemokine receptors
  • a particular chemokine signals in multiple receptors
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11
Q

what do some viruses make

A

make chemokines so it interferes with the immune system

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12
Q

what is the function of chemokine

A
  • Control adhesion,
  • chemotaxis
  • activation
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13
Q

name the pro inflammatory cytokines

A
  • IL-1
  • IL-6
  • TNF- alpha
  • IFN gamma
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14
Q

name the anti-inflammatory cytokines

A
  • IL-10

- TGF beta

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15
Q

What happens when there is a damage inflammatory response

A
  • Damage or infection causes activation of macrophages
  • Activated macrophages release cytokines (e.g. TNF – alpha)
  • These cytokines recruit leukocytes to the area (e.g. neutrophils, eosinophils, lymphocytes, monocytes)
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16
Q

what are the roles of cytokines

A
  • Immune cell recruitment
  • T cell clonal expansion
  • Differnetiation of CD4+ T helper cells
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17
Q

describe immune cell recruitment

A

Cytokines act on the endothelium causing the lymphocytes to stick to the endothelium, migrate and move through the capillary
Sticky
- Tethering – the cell tethers to the endothelium, this enables the immune cell to roll along the vessel wall. This initial reaction is caused as cytokines make the lining of the blood vessels more sticky
- Rolling and activation – as the rolling occurs if there is chemokines present they activate adhesion molecules and allow rest
- Arrest – this is when the cell stops
- Diapedesis and migration – cell can cross the endothelium

18
Q

what is the role of cytokines in immune cell recruitment

A

TNFa increases ‘stickiness’ of endothelium by increasing expression of adhesion molecules:
- Release from Weibel-Palade bodies (WP) -rapid
- New synthesis –takes longer
Chemokines activate adhesion molecules (called integrins) to increase binding now cell can arrest (stop)
This is called inside out signalling, signal from the inside of the cell to the outside of the cell causing the molecules to change there conformation

19
Q

describe how T cell clonal expansion works

A
  • When T cells recognise a pathogen (binding of TCR on CD4 T cell and MHC on APC)
  • Autocrine signalling
  • Activation causes both production of IL-2 and expression of a high affinity IL-2 receptor causes this
20
Q

describe what are the things that make cytokines harmful

A
  • Septic shock
  • Toxic shock syndrome
  • Cytokine storm
  • Chronic over production which leads to inflammatory conditions
21
Q

what do people with mutations in their IL-10- receptor gens develop

A

genes develop very severe gut inflammation early in life and need bone transplantation

22
Q

Describe how septic shock works

A
  • Controlled local production of TNF alpha is good, this is produced in a local bacterial infection for example TNF alpha and IL-1 and IL-6 cause fever (prevent any more pathogens), acute phase proteins and immune cell production
  • Wide spread bacterial infection which is sepsis can lead to overproduction of cytokines which lead to septic shock and Hyperactivation of TNF alpha, IL1 and IL6 this leads to septic shock
23
Q

what are the symptoms for septic shock

A
  • Loss of blood pressure
  • Fever
  • Diarrhoea
  • Clotting
  • Death
24
Q

what is toxic shock syndrome

A
  • super antigens activate many T cells and drive overproduction of cytokines
25
Q

what is a cytokine storm

A
  • When cytokine production becomes uncontrolled a potentially fatal positive feedback loop is established leading to a cytokine storm
26
Q

How do cytokine storms work

A
  • Immune system produces cytokine
  • Immune cell produces more cytokine
  • Cytokine stimulates immune cell
  • Immune cell produces cytokine
27
Q

what are examples of cytokine storms

A
  • Occurs in a number of viral infections
  • Ebola
  • SARAS
  • Bird Flu
28
Q

What does chronic overproduction lead to

A

inflammatory conditions such as

  • Asthma
  • IBD
  • Psoriasis
  • Rheumatoid arthritis
  • Type 1 diabetes
29
Q

How does Atopy occur

A
  • Over production of IL-4 causes TH2 dominant response
  • This causes overproduction of IgE which leads to degranulation of mast cells (this is because IgE binds to the surface of mast cells which have a higher affinity for them)and causes asthma and allergies
30
Q

How is chron’s disease caused

A
  • Over production of IL-12 and IL-23 lead to TH1 causing over production of TFN gamma and alpha – leads to activation of innate immune cells and tissue damage such as chrons disease
  • Environment is important – migration – children have incidence of chrons disease have the high disease incidence
31
Q

what are monoclonal antibodies

A
  • Monoclonal antibodies are antibodies that can be used to block the action of cytokines
32
Q

what is an example of a monoclonal antibody

A
  • For example Infliximab (anti-TNFa) can be used in Chron’s, rheumatoid arthritis, psoriasis
33
Q

describe stein et al

A

Amish – single family fairy farms and hutterite – mechanised farming
- They both originally come from parts of Europe so genetically they are similar
Amish
- Have 6-8 x lower in allergy and asthma prevalence
- Found they have altered innate immune cell populations and gene expression
- House hold dust; endotoxin levels 7x higher, distinct microbes, inhibits asthma in mouse model
- Duct developed activity in the immune system protected people later in life from asthma and allergies

34
Q

what is the hygiene hypothesis

A
  • Epidemiological evidence suggests exposure to microbes early in can protect against immunological diseases
  • Modern hygiene may reduce these protective exposures but mechanisms not clear ‘
35
Q

what is the problem in administering cytokines

A

has a short half live in vivo attaining an effective dose

- half life for IV IL-2 is 7-10 minutes

36
Q

How is interferon A used

A
  • Roferon, used in treatment of hepatitis B infection & some cancers
37
Q

How is GM-CSF used

A
  • Leukine, used to stimulate production of myeloid cells after bone marrow transplantation
38
Q

How do antiviral actions of IFN alpha and IFN beta work

A
  • Engagement of PRRs by viruses stimulates the production of IFNs – (plasmoacytoid DC especially good at this )
  • Increase MHC expression, activate NH cells
  • IFNs induce a resistant state in adjacent cells
39
Q

what is an agent that you administer to block cytokines

A

monoclonal antibodies

  • soluble receptors such as TNF-alpha receptor entraceptment
  • redundancy is a major challenge when targeting many cytokines
40
Q

What does Anti- TNF alpha therapy do

A
  • Major impact on treatment of crohns disease rheumatoid arthritis, psoriasis
  • But:
  • Some patients don’t respond
  • Some lose response
  • Potential complications with infection & malignancy
  • Many anti-cytokine therapies have not worked well

FunMed Immunology (6 decks)

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