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Flashcards in Cytokines Deck (40)
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1

describe cytokines

  • cytokines: low molecular weight proteins (MW <30 kDa) that regulate the immune response
    • over 200
    • secreted by a broad group of cells, but mainly by TH cells, dedritic cells and macrophages
    • carefully regulates (no constitutive)
    • act mostly locally

2

define interleukins, lymphokines, monokines, colony stimulating factor and chemokines

  • interleukins (ILs): group of cytokines secreted by leukocytes that act on leukocytes
  • lymphokines: produced mainly by lymphocytes
  • monokines: produced mainly by monocytes
  • colony stimulating factor: support growth of cells on semi-solid media
  • chemokines: cytokines that mediate chemotaxis

3

describe the mechanism of action of cytokines

  • bind to specific membrane receptors
  • high affinity; work at low concentrations (picomolar)
  • trigger signal transduction leading to gene expression
  • modulate immune response; stimulate/inhibit activation, proliferation, differentiation of immune cells

4

name the 5 cytokine receptor families

(chemokine receptor family not shown)

5

describe IL-2R (cytokine receptors: class I)

  • IL-2R is the most thoroughly studied cytokine receptor
    • expressed by T cells for proliferation
      • also called CD25, surface marker in mature T cells
    • complete receptor has 3 subunits--subunits together have higher affinity for IL-2

6

describe signalling via class I and class II cytokines

  • initiated by cytokine binding
  • activates JAK (Janus kinase)
  • phosphorylation of tyrosine
  • binding of STAT (signal transducers and activators of transcription)
  • translocation of STAT to cell's DNA
  • transcription of specific target genes 

7

describe homeostatic vs. inflammatory chemokines

  • homeostatic: constitutively produced in thymus and lymphoid tissue and are responsible for basal leukocyte migration
  • inflammatory: these are formed under pathological conditions
    • stimualted by IL-1, TNF-a, LPS or viruses 
    • actively participate in the inflammatory response attracting immune cells to the site of inflammation
    • examples: CXCL8, CCL2 (MCP-1), CCL3 (MIP-1a), CCL5 (RANTES)

8

summarize the cytokines found in innate and adaptive immunity

9

describe the hematopoietic cytokines

10

describe the lineage of cells from a hematopoietic stem cell and the ILs involved 

11

contrast the function of Th1 vs Th2 cytokines

  • Th1 cytokines activate macrophages, NK cells, and cell mediated immunity, plus the secretion of IgG isotypes
    • IgG production/complement fixation
    • macrophage activation
    • delayed type hypersensitivity (cell-mediated)
    • cytotoxic T-lymphocyte production
  • Th2 cytokines tend to favor isotype switching in the humoral immune response
    • IgE production
    • eosinophils

12

describe teh Th1/Th2 balance

  • in a given immune response, either a Th1 or a Th2 response may dominate
  • T helper cell cytokines of one response tend to down-regulate the other type of response
    • example: Th1 cells secrete IFN-γ, which inhibits expansion of the Th2 subset
  • balance of two subset determines response to disease
    • example: leprosy
      • tuberculoid (Th1, CMI response, good prognosis)
      • lepromatous (Th2, humoral response, bad prognosis)

13

summarize the Th1/Th2 balance

14

describe the role of cytokiens in disease

  • septic shock:
    • bacterial endotoxin (LPS) binding to TLRs
    • overproduction of IL-1 and TNF-a
  • toxic shock:
    • bacterial superantigens non-specifically activate T cells
    • overproduction of IL-1 and TNF-a
  • rheumatoid arthritis
    • TNF-a
  • lymphoid and myeloid cancers
    • high levels of IL-6

15

describe the timeline of cytokine production

16

describe CXCL-8 (IL-8) (chemokine)

  • chemoattractant for neutrophils (CXCR1, CXCR2)

17

describe CCL19/CCL21 (chemokine)

  • plays an important role in trafficking of T cells in thymus and in T cell and B cell migration to secondary lymphoid organs (receptor CCR7)

18

describe CCL5 (RANTES) (chemokine)

  • chemotactic for T cells, eosinophils, and basophils
  • plays an active role in recruiting leukocytes into inflammatory sites
  • induces the proliferation and activation of certain NK cells

19

describe CCL2 (MCP-1) (chemokine)

  • monocytic chemotactic protein-1
  • chemoattractant for monocytes, T-cells, mast cells, basophils, stem cells

20

describe CCL3 (MIP-1a)

  • macrophage inflammatory protein-1a
  • chemoattractant for monocytes, T- and B-cells, NK cells, mast cells, basophils, dendritic cells, stem cells

21

describe IL-2 (cytokines that regulate adaptive immunity)

IL-2

  • source: Th1 cells
  • activity: T cell growth factor

22

describe IL-4 (cytokines that regulate adaptive immunity)

IL-4

  • source: Th2 cells
  • activity: B cell growth factor

23

describe IL-5 (cytokines that regulate adaptive immunity)

IL-5

  • source: T cells
  • activity: B cell growth and immunoglobulin synthesis

24

describe IL-7 (cytokines that regulate adaptive immunity)

IL-7

  • source: marrow/thymic stromal cells
  • activity: pre-B and pre-T cell growth factor

25

describe IL-9 (cytokines that regulate adaptive immunity)

IL-9

  • source: T cells
  • activity: activates mast cells 

26

describe IL-10 (cytokines that regulate adaptive immunity)

IL-10

  • source: Th2 cells and macrophages
  • activity: inhibits Th1 and macrophage function

27

describe IL-12 (cytokines that regulate adaptive immunity)

IL-12

  • source: B cells and macrophages
  • activity: activates NK cells, Th1 proliferation

28

describe TNF-B (cytokines that regulate adaptive immunity)

TNF-B

  • source: T cells
  • activity: killing by cytotoxic CD8 cells

29

describe IL-1 (cytokines that regulate innate immune response)

IL-1

  • source: monocytes, macrophages
  • activity: systemic inflammatory efefct, including fever, acute-phase protein synthesis, T-cell activation

30

describe IL-6 (cytokines that regulate innate immune response)

IL-6

  • source: T cells, other cells
  • activity: stimulates other T cells to produce IL-2, B cells to produce immunoglobulins and stem cells