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Biopharmaceutical Science > Interleukins > Flashcards

Interleukins Flashcards

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Biology 101 flashcards
1
Q

What do interleukins consist of

A

33 different constituent members

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2
Q

What do interleukins regulate

A
  • Normal and malignant cell growth
  • All aspects of immune response
  • Regulation of inflammation
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3
Q

Interleukin 2 (IL-2)

A
  • Aka T-Cell growth factor
  • First T-Cell growth factor to be identified
  • Produced exclusively by T-lymphocytes in response to antigen stimulation
  • Role in the immune response
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4
Q

Structure of IL-2

A
  • Single chain glycoprotein
  • Contains 133 amino acids
  • Globular structure - consists of 4 a helical structures and no b conformation
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5
Q

Function of IL-2

A
  • Acts as a central autocrine growth factor for T cells - magnitude of t cell response dependant on IL-2 production
  • growth factor for activated B lymphocytes
  • stimulates enhanced antibody production and secretion
  • Promotes the growth and differentiation of NK cells to form lymphokine activated killer cells.
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6
Q

How was IL-2 produced before recombinant DNA technology?

A

produced by transformed cell lines - Jurkat leukaemia cell line

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7
Q

How is large-scale IL-2 production achieved today?

A

heterologous expression against and E. coli background

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8
Q

Recombinant IL-2 preparation

A

Tradename: Proleukin
Manufactured by: Chiron

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9
Q

how does Proleukin differ from IL-2

A

non-glycosylated
lacks N-terminal alanine
cys 125 residue has been replaced by a serine

Yet they display same bio activities

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10
Q

What is the significance of IL-2 in cancer treatment?

A
  • Experiments in the 1980s showed that lymphocytes incubated with IL-2 could kill a range of cancer cell lines, including melanoma and colon cancer.
  • IL-2 stimulated NK cells (LAK) mediate cancer cell destruction.
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11
Q

How is IL-2 used to promote tumour regression in cancer patients?

A
  • LAK cells purified from a patient’s blood and activated with IL-2 in vitro
  • Reintroduced into the patient along with more IL-2.
  • Complete tumour regression in 10% of patients with melanoma or renal cancer
  • Partial regression in 10-25% of such patients.
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12
Q

What are tumour-infiltrating lymphocytes (TILs)?

A
  • IL-2 stimulated cytotoxic T cells
  • Cytotoxic T-lymphocytes that specifically bind to the tumour antigen - tumour-specific cells.
  • These cells can be isolated from a tumour biopsy and further activated with IL-2 in vitro.
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13
Q

How effective is IL-2 treatment in promoting tumour regression in cancer patients?

A
  • Further activation of TILs with IL-2, followed by reintroduction into the patient along with more IL-2, promotes tumour regression in >50% of treated patients.
  • Additional cancer types, such as ovarian and bladder cancer, non-Hodgkin’s lymphoma, and acute myeloid leukemia, have also shown partial responsiveness to IL-2 treatment.
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14
Q

What are intracellular pathogens?

A

microbial pathogens that replicate within host cells.

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15
Q

Why are intracellular pathogens difficult to treat?

A
  • They hide within host cells and evade the immune system.
  • They can also develop resistance to antibiotics.
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16
Q

What are some examples of intracellular pathogens?

A
  • Mycobacterium tuberculosis
  • Listeria monocytogenes
  • Legionella pneumophila.
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17
Q

What type of immune response is raised against intracellular pathogens?

A

Largely a T-cell response.

18
Q

How might IL-2 be useful in the treatment of intracellular pathogens?

A

IL-2’s ability to stimulate T-cells renders it useful

19
Q

What medical conditions are caused or exacerbated by the immune system itself?

A
  • Autoimmune diseases
  • Tissue/organ transplantation rejection
20
Q

How is selective immunosuppressant activity achieved in idividuals suffering with autoimmune diseases or organ rejection?

A

By preventing the synthesis or functioning of IL-2

21
Q

example of immunosuppressive for IL-2

A

Cyclosporin A

  • One of the foremost immunosuppresive agents currently in use
  • Functions by preventing IL-2 synthesis
22
Q

What are alternative approaches to IL-2 targeted immunosuppression?

A
  • Soluble IL-2 receptor that competes with native receptor for binding of IL-2
  • IL-2 varients that retain the ability to bind but fail to initiate signal transduction
  • Monoclonal antibodies that block IL-2 binding
23
Q

What are some examples of monoclonal antibodies that are capable of blocking IL-2 binding?

A

Zenapax and Simulect

24
Q

Interleukin-1 (IL-1)

A
  • also known as lymphocyte-activating factor (LAF)
  • endogenous pyrogen
  • catabolin
25
Q

Forms of IL-1

A

two distinct forms: IL-1α and IL-1β.

26
Q

What cells produce IL-1

A

a wide range of cells, in varying ratios.

27
Q

What is the structure of IL-1α and IL-1β?

A
  • Globular proteins
  • Composed of 6 strands of antiparallel β pleated sheets.
  • Only 20% aa sequence identity but both bind to the same receptor & induce similar biological activities.
28
Q

IL-1 biological activities

A
  • Proinflammatory cytokine - promotes synthesis of substances involved in generating inflammatory mediators.
  • Role in activating B-Lymphocytes
  • Synthesis of acute-phase proteins in hepatocytes with IL-6
  • Acts as co stimulator of haematopietc cell growth/differentiation
29
Q

IL-1 receptor antagonist (IL-1Ra)

A
  • Third IL-1-like protein
  • binds to IL-1 receptor without triggering an intracellular response
30
Q

Acute-phase proteins (APPs)

A

an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation.

31
Q

Approaches to modulating IL-1 activity

A
  • Anti-IL-1 antibodies
  • Soluble IL-1 receptor
  • The native IL-1 receptor antagonist (IL-1Ra)
32
Q

IL-1 mediated condition

A

Rheumatoid arthritis
characterised by the presence of high levels of IL-1 in the synovial fluid of affected joints

33
Q

Additional negative influences of IL-1

A

Cartilage degradation and bone resorption

34
Q

Recombinant form of IL-1Ra for treating rheumatoid arthritis

A

Kineret

35
Q

Kineret

A

approved product for treating rheumatoid arthritis based on IFN-1Ra

36
Q

How does kineret differ from native form

A
  • Non-glycosolated
  • Contains an additional N terminal methionine residue
37
Q

Additional approach to IL-1 down regulation

A

inhibiting the proteolytic enzymes that realease the active interleukin fromits native inactive precursor

38
Q

Example of additional approach to IL-1 down regulation

A

IL-1b converting enzyme (ICE) which releases active IL-1b from its precursor

39
Q

What produces Interleukin 11 (IL-11)

A

IL-1 activated bone marrow stromal cells (connective tissue cells) and fibroblasts (stroma synthesising cells)

40
Q

Function of IL-11

A

Haematopietic growth factor
Stimulates:

  • growth/differentiation of bone marrow cells
  • Thrombopoiesis
41
Q

What is Neumega?

A
  • Tradename of an IL-11-based product that has been approved for the prevention of thrombocytopenia.
  • It works by stimulating platelet production and can partially offset the damage caused by chemotherapy.

Biopharmaceutical Science (12 decks)

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