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Immunology Exam 1 > Lecture 5 - Cytokines > Flashcards

Lecture 5 - Cytokines Flashcards

1
Q

What are cytokines?

A

small soluble proteins and glycoproteins that regulate and mediate host immune response via direct action on cells

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2
Q

What are some features of cytokines?

A
  • large number of them and variety
  • have significant homeostatic roles in host defense
  • acts locally or at a distance
  • rapidly activate or suppress immune activities
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3
Q 
cell source? 
target cell? 
activities? 
effect? 
concentration?
A 
numerous, 
many, 
pleiotropic and overlapping,
autocrine, paracrine and endocrine, 
picomolar
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4
Q

General properties of cytokines

A
  • not antigen-specific (act on other host cells)
  • individual cytokines are pleiotropic and may have different activities in different situations/conditions
  • may be made by more than one cell type
  • may act on many cell types
  • usually show brief, highly regulated expression
  • have overlapping, redundant actions
  • influence the synthesis of other cytokines
  • influence the action of other cytokines
  • signal through specific receptors
  • have many non-immune functions
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5
Q

What are the 4 families of cytokines?

A

Growth Factors, Interleukins, Interferons, Chemokines

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6
Q

How are families grouped?

A

based on functional activity

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7
Q

What is the fn of GFs?

A

stimulators of hematopoiesis that regulated immature leukocyte growth and differentiation –> drive terminal differentiation of hematopoietic progenitors

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8
Q

Give an example of some GFs

A

Granulocyte-colony stimulating factor (G-CSF)

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9
Q

What is the fn of ILs?

A

mediators and regulators of lymphocytes and leukocytes –> regulators of both innate and adaptive fns of other immune cells.
-gp is very diverse in structure and fn

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10
Q

Give an example of ILs?

A

IL-2, tumor necrosis factor - alpha

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11
Q

What is the fn of IFNs?

A

mediators and regulators of antiviral and innate immunity –> can activate intracellular processes that inhibit viral replication
-several are key regulators of macrophage activity and tolerance of developing fetus

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12
Q

Give an example of IFN?

A

IFN-2

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13
Q

What is the fn of Chemokines?

A

chemoattractants - regulate the directed movement of immune cells (WBCs) from blood into tissues

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14
Q

Give some features of cytokine receptors

A
  • expressed on many cell types and show considerable regulation of expression
  • highly specific for their ligand
  • can be single subunit or multimeric
  • some share common subunits
  • can be grouped into families based on signal transduction mechanisms or molecular structure
  • a cell can express receptors for many cytokines
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15
Q

How many types of IFNs?

A

3-5 IFN with related structure expression in response to immune stimulation
-IFN alpha/beta, IFN-2

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16
Q

What’s the fn of IFN-alpha/beta?

A
  • consists of a family of glycoproteins
  • involved in anti-viral activity
  • released from virus-infected cells of all types (T cells, macrophages and fibroblasts are primary sources)
  • can also accelerate the differentiation of B cells –> influencing Ab response to specific Ag
  • **inc MHC class I expression –> greater chance of encountering cytotoxic T cell
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17
Q

Describe the antiviral activity of IFN-a/b

A

1) antiviral proteins that activate host genes to inhibit viral RNAs and replication
2) induce MHC class I expression on the host cells
3) activate NK cells to kill virally-infected cell

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18
Q

What produces IFN-gamma?

A

mainly T helper cells and NK cells

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19
Q

What’s IFN-gamma fn?

A
  • most potent activator of macrophage immune fn
  • stops macrophage migration
  • activates proinflammatory cytokine gene expression
  • augments phagocytosis
  • increases anti-tumor and antibacterial processes
  • upregulates MHC expression
  • influences production of immunoglobulin isotypes
  • stimulates neutrophil respiratory burst
  • activates vascular endothelial cell adhesion molecule expression
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20
Q

Describe the 4 main functions of IFN-gamma

A

1) macrophage activation
2) isotype switching
3) development of TH1 effector cells
4) increased MHC expression, Ag presentation

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21
Q

What are foals born with?

A

IFN-gamma deficiency –> susceptible to bacterial infections

22
Q

What’s the fn of Colony-stimulating factors?

A
  • promote terminal differentiation of polypotent progenitor cells
  • many expressed in certain tissues, all show altered expression during inflammation
23
Q

Give some examples of CSF?

A

G-CSF (granulocyte colony-stimulating factor): neutrophils, eosinophils
Macrophage CSF: monocyte/macrophages
GM-CSF: macrophages or granuloctyes
IL-3: macrophages or granulocytes
IL-7: produced by stromal cells in bone marrow or spleen; proliferation of lymphoid progenitors
IL-11: megakaryocytes

24
Q

True or False: hematopoiesis is not static

A

True; many cytokines affect differentiation of leukocytes, and how many cells of a given cell type are produced in the bone marrow can change during inflammatory events because the cytokines produced change over time

25
Q

What produces IL-1?

A

wide variety of cell types especially activated macrophages and epithelial cells
-exists in 2 forms: IL-1a and IL-1b (overlapping activities)

26
Q

What’s the fn of IL-1?

A
  • principal regulator of the host inflammatory response
  • Fever induction
  • adhesion molecule expression (vascular endothelial)
  • acute phase protein expression (hepatocytes)
  • activate T cell proliferation during Ag presentation
  • synergizes with IL-2 to regulate B cell proliferation
  • induces epxression of IL-6 by hepatocytes and macrophages
27
Q

What produces IL-2?

A

activated T helper 1 cells

28
Q

What’s the fn of IL-2?

A
  • cause autocrine proliferation of T cells
  • primary growth factor for T cell proliferation
  • regulates proliferation of B cells, augments Ig synthesis
  • stimulates T cytotoxic cell and NK cell activity against tumors
  • enhances macrophage fn
29
Q

How does IL-2 affect T cell proliferation?

A

naive T cell recognizes an Ag on surface of an APC responds to IL-2 by undergoing a burst of replication prior to terminal differentiation to effector cells

30
Q

What produces IL-6?

A

activated macrophages, T cells, fibroblasts and stromal cells of the bone marrow

31
Q

What’s the fn of IL-6?

A
  • wide variety of effects on different target cells
  • acute phase reactant production (liver)
  • endogenous pyrogen which acts on hypothalamus to cause fever
  • induces IL-2 expression
  • promotes CD8+ T cell differentiation and activation
  • acts as cofactor for IgM and IgA synthesis
32
Q

What produces IL-12?

A

primarily by dendritic cells and macrophages

-has several subunits synthesized at diff rates

33
Q

What’s the fn of IL-12?

A

critical cyotkines that influences differentiation of naive T cells toward T helper 1 pathway (imp for determining type of immune response that perdominates)
-activates NK cells to secrete IFN-gamma

34
Q

What produces Tumor Necrosis Factor (TNF-alpha)

A
  • principal mediator of endotoxic shock (Gram- sepsis)
  • hepatocyte: proliferation (liver regeneration), acute phase protein expression
  • macrophage: decreased proliferation, terminal differentiation, increased phagocytosis, adhesion molecule secretion
  • endothelial cells: IL-1 expression, adhesion molecule expression
  • tumor cells: cytolysis
  • elicits fever
35
Q

What are the local and systemic effects of TNF?

A

release of TNF induces local protective effect, but can cause damage when released in excess or systemically.

  • pleiotropic cytokine has numerous and powerful effects on other cells and systems
  • causes leaky channels
  • **low quantities: local inflammation
    moderate: systemic effects
    high: septic shock
36
Q

Cytokines synergize to do what? What can cytokine storms cause?

A

impact peripheral immune events and “cytokine storms” can lead to tissue injury, shock and death

37
Q

What causes endotoxic or septic shock?

A

overexpression of cytokines (can be induced by products derived from gram- cell walls - LPS or endotoxin) –> induce shock characterized by rapid rise in temperature, vascular leakage, intravascular coagulation, acute phase production and eventually multiorgan failure

38
Q

What is the major cytokine responsible for pathogenesis of septic shock?

A

TNF-alpha; produced so quickly that damage is done by time of tx

39
Q

Do mammalian species vary in their sensitivity to LPS-induced shock?

A

yes; cat/horse/pig/sheep>dogs>mice»birds

40
Q

During shock, what do cytokines mediate?

A

intravascular coagulation –> cold extremities, low BP, organ injury, rapid HR, rapid shallow breathinng

41
Q

What produces IL-4 and IL-10?

A

Th2 cells, but activated mast cells release IL-4 from stored vesicles

42
Q

What’s the fn of IL-4 and IL-10?

A

considered anti-inflammatory

  • T cells: promotes growth of TH2 cells, enhanced proliferation, production of TH2 cytokines, inhibition of TH1 differentiation
  • macrophages: inhibits activation
43
Q

What produces chemokines?

A

phagocytic cells, T cells, endothelial cells and fibroblasts –> induced by a variety of stimuli during inflammation
-divided into 4 classes based on AA seq (species variation in some genes)

44
Q

What’s the fn of chemokines?

A

families of small cytokines which regulate the migration of immune cells into inflammatory loci (contribute to coordination of immune response and inflammation)
***IL-8, MIP-1a, RANTES (coordinates migration of neutrophils, naive T cells, monocytes, NK cells)

45
Q

How do B and T cells communicate?

A

using cytokines for both initial activation of B cells, for B cell differentiation into plasma cells, and for Ig class switching (isotype switching)

46
Q

Give an example of B and T cells communicating with cytokines

A

ex: cytokines produced by B cells when present Ag –> influence TH0 cells to differentiate into TH2 cells –> augmenting humoral immune responses
ex: assist in Ab isotype switching –> impacts effectiveness of adaptive immune response

47
Q

T cells generated can influence what?

A

disease outcome based on cytokines they produce –> often determined by unknown genetic factors of host animal

48
Q

How does disease relate to cytokines?

A

numerous diseases known to have a dysregulated cytokines associated with severity or onset
-particularly transplant rejection –> inhibited via cyclosporin A tx and inflammationwhich can damage host cells –> regulated via corticosteroids which inhibit proinflammatory cyotkine production

49
Q

What are many cytokine genes regulated by?

A

txn factor NF-kB

50
Q

What inhibits NF-kB?

A

steroids inhibit NF-kB activation of cytokines –> limiting inflammation

51
Q

What is used for rheumatoid arthritis?

A

anti-TNF-alpha therapy

Immunology Exam 1 (7 decks)

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