1887

Chapter 15 : Cellular Communication

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Cellular Communication, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816148/9781555812461_Chap15-1.gif /docserver/preview/fulltext/10.1128/9781555816148/9781555812461_Chap15-2.gif

Abstract:

Cellular growth and differentiation ensue, leading to a specific immunologic response. The basic components of the immune system that interact, and therefore must communicate with each other, include antigen-presenting cells (APCs), T cells, and B cells. B cells also function as APCs for certain types of T cells. In addition, the activity of other participatory cells, principally leukocytes, including monocytes/macrophages and the granulocytes, is also influenced by cellular communication. Almost every aspect of cellular communication and interaction in the immune system is modulated in some way by these molecules. Chemokines are a large family of structurally related chemoattractant proteins 8 to 10 kDa in size. They serve as soluble mediators of inflammation and cellular communication and are derived from a variety of cells, with platelets, lymphocytes, activated monocytes/macrophages, and granulocytes being among the prime producers of chemokines. The major function of interleukin (IL)-8 is neutrophil activation and recruitment. IL-8 also augments production of lysosomal enzymes by neutrophils and increases a variety of cell-adhesion molecules. Recent evidence suggests that IL-8 is a dimeric molecule bearing considerable homology to the human major histocompatibility complex (MHC) class I molecule. Cell-adhesion molecules, such as lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), as well as very late activation 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1), found on lymphocytes and leukocytes, have been found to participate in antigen-dependent and antigen-independent T-cell responses.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15

Key Concept Ranking

Immune Receptors
0.61326313
Tumor Necrosis Factor
0.49602926
Immune Systems
0.47521794
White Blood Cells
0.47339606
0.61326313
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 15.1
Figure 15.1

Communication between various cells of the immune system relies on both cell contact-dependent signals such as TCR and MHC and CD80 or CD86 and CD28 as well as soluble signals mediated by factors such as cytokines and lipid mediators.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.2
Figure 15.2

The cytokine IL-2 pro- vides a crucial soluble signal during the activation of a T cell. A naive T cell is presented with cognate antigen peptide complexed to self MHC and also receives sufficient costimulation via CD80 (or CD86)-CD28 interactions. This is sufficient to begin the process of T-cell activation but is not sufficient to cause the T cell to enter the cell cycle. The partially activated T cell produces both IL-2 and a high-affinity receptor for IL-2. Binding of IL-2 by the same cell that synthesized it (termed autocrine activity) provides the T cell with the final signal it needs to begin proliferating.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.3
Figure 15.3

T-cell–B-cell interactions involve the increased expression of many counterreceptors by both cells. Activation of B cell begins with either binding of antigen (Ag) by the B-cell antigen receptor (BCR) or binding of a ligand such as bacterial LPS by a pattern-recognition receptor such as a TLR and CD14. These early activation events result in increased expression of CD80 and CD86 by the B cell. Initial activation of the T cell requires both antigen-MHC recognition by the TCR and costimulation such as CD28 binding to CD86. Early T-cell activation results in increased expression of CD40L. CD40L binding to CD40 is an essential signal to stimulate isotype switching in the B cell. Later in T-cell activation, the T cell increases its production of CTLA- 4. CTLA-4 binds to CD80 on the B cell, inactivating the T cell and returning the immune system to a quiescent state.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.4
Figure 15.4

Cell-cell interactions are promoted by several families of cell-adhesion molecules (CAMs). Glycoprotein CAMs called are recognized by carbohydrate-binding CAMs that belong to the selectin family. CAMs of the family possess a high-affinity binding site for CAMs of the .

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.5
Figure 15.5

Cytokine action is characterized by several qualities. Pleiotropism is the ability of one cytokine (for example, IL-5) to affect different target cells, causing different effects in each target cell type. Redundancy is the ability of two different cytokines to cause the same effect on the same target cell. In the example shown, IL-19 and IL-20 can cause the same inflammatory responses in keratinocytes because the two cytokines bind to the identical receptor. Antagonism is the ability of one cytokine to inhibit the action of another. In the example shown, IL-10 inhibits the action of IL-12 by preventing IL-12 from being synthesized.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.6
Figure 15.6

Cytokines can act on target cells that are proximal or distant from their point of synthesis. Some cytokines exhibit autocrine activity, meaning that the cytokine exerts an effect on the same cell that synthesizes it. The example shown is IL-2, which is an autocrine growth factor on T cells because the same T cell synthesizes both the cytokine and the cytokine receptor. Cytokines can also act on target cells that are different from the cell that synthesized the cytokine but are still near the cytokine-producing cell. This is termed paracrine activity. Last, cytokines can act on target cells that are distant from their site of synthesis. In the example shown, IL-6 produced by macrophages at the site of a localized infection can enter the bloodstream and act on hematopoietic stem cells in the bone marrow, triggering increased generation of some white blood cell types

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.7
Figure 15.7

Cytokines can be detected through bioassays that utilize cytokine-responsive indicator cells. CTLL-2 is a cell line that proliferates in response to IL-2. If cell culture supernatant containing an unknown quantity of IL-2 is added to a vessel containing CTLL-2 cells, the CTLL-2 cells will proliferate according to how much IL-2 is present in the unknown supernatant. CTLL-2 cell proliferation can be quantitated by carrying out the experiment in the presence of radiolabeled nucleotides (typically [3H]thymidine); in this case, the amount of CTLL-2 cell proliferation will be directly proportional to the amount of radioactivity incorporated into their DNA. A sample experiment. A standard curve is generated by culturing CTLL-2 cells in [3H]thymidine as well as known quantities of IL-2 (green data points). The amount of IL-2 in the unknown sample (red data point) is then compared to the standard curve. In the sample experiment, the unknown sample caused CTLL-2 proliferation consistent with approximately 300 units of IL- 2. Quantities of some cytokines such as IL-2 are routinely expressed in , since they are so unstable that expressions of mass (such as nanograms) are impractical or misleading.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.8
Figure 15.8

Cytokine synthesis can be detected by reverse transcription- PCR (RT-PCR) amplification using cytokine gene-specific primers. mRNA is isolated from the cell of interest (in this case, a T cell). The first step is to convert all of the mRNA into DNA. This is performed by the enzyme reverse transcriptase, which can elongate a primer to synthesize a cDNA strand from each mRNA strand. The primer used for this step is an oligodeoxythymidine [oligo(dT)] primer, which can anneal to the poly(A) tails of all mature mRNAs. These steps are depicted at a higher magnification to emphasize annealing of the oligo(dT) to the poly(A) tails. Reverse transcription yields an RNA-DNA heteroduplex. The RNA strand of this heteroduplex is then degraded by the enzyme RNase H and is replaced with a second DNA strand using a DNA polymerase. Cytokine gene mRNA (blue) is then selectively amplified by PCR using primers (short black lines) that specifically anneal to cytokine gene sequences. Each cycle of PCR amplification consists of “melting” the DNA duplexes, allowing the cytokine gene-specific primers to anneal, and then using polymerase to synthesize a complementary DNA strand from the cytokine-specific primer. This results in an exponential amplification of only the cDNA derived from cytokine mRNA. After 20 to 30 cycles of amplification, there is a sufficient amount of cytokine PCR product to detect on an ethidium bromide-stained agarose gel. This type of experiment can be used to measure changes in cytokine gene expression. In the example shown, the RT-PCR experiment is performed on mRNA isolated from resting or activated T cells. Analysis of the RT-PCR products from these two samples shows that the activated T cells contain more cytokine mRNA than the resting cells.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.9
Figure 15.9

Structural motifs of the four families of chemokines. The C family, CC family, and CXC family are soluble proteins with conserved cysteine residues (C) at the indicated locations. X indicates the presence of any other amino acid that intervenes between the conserved cysteines. The CX3C family thus far contains only one member: fractalkine. Fractalkine is a transmembrane protein comprising a membrane-distal domain that contains a structural motif similar to that of chemokines of other families. This domain is followed by a stalk region, and then the transmembrane (TM) and cytoplasmic regions. Modified from S. G. Ward and J. Westwick, (Part 3):457–470, 1998, with permission.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.10
Figure 15.10

Signaling through chemokine receptors utilizes heterotrimeric G proteins. The G protein exists in an inactive state in the cytoplasm, bound to GDP. Chemokine binding allows the chemokine receptor to bind the G protein and function as a guanosine exchange factor, causing the G protein to release the GDP and bind GTP. This activates the G protein. The active subunits of the G protein (Gα-GTP and Gβγ) initiate multiple signaling pathways that are still undefined but are known to include the mitogen-activated protein kinase (MAPK) pathway and the transcriptional activator NF-AT (nuclear factor of activated T cells). After signal transduction is complete, the Gα subunit cleaves its bound GTP to GDP, allowing the Gα subunit to reassociate with the Gβγ subunit and inactivate the G protein.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.11
Figure 15.11

The GM-CSFR subfamily and IL-2R subfamily of the type I cytokine receptor family. Each receptor is a heterodimer or heterotrimer. The gray ovals represent the bound cytokine. Receptor names are listed above each receptor, and subunit names are listed below each subunit. Subunits with signal transduction capacity are indicated by a lightning bolt icon on their cytoplasmic tail. Within each subfamily, all receptors share a common signaling subunit (the β subunit in the GM-CSFR subfamily and the γc subunit in the IL-2R subfamily) but also contain other subunits that are unique to each receptor and confer cytokine specificity on the receptor. In the GM-CSFR subfamily, the receptor-specific subunit (the α subunit) is able to bind the cytokine alone, without the β subunit. However, the α subunit alone only binds the cytokine with low affinity and fails to transduce a signal upon binding. The β subunits of the IL-2R and the IL-15R are identical.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.12
Figure 15.12

The IL-2 receptor exists in three forms, depending on which receptor subunits are expressed by the cell. The α chain alone is a low-affinity receptor. A complex of the β and γc subunits comprises the intermediate-affinity receptor. A complex of all three subunits comprises the high-affinity receptor. Only the intermediate- and high-affinity receptors can transduce signals. The α subunit is not expressed on resting T cells but is expressed on T cells following activation. Therefore, resting T cells express only the intermediate-affinity receptor, whereas activated T cells express the high-affinity and (due to overexpression of the α subunit) low-affinity receptors.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.13
Figure 15.13

Receptors of the hematopoietin family and interferon family signal via the JAKs and STAT family of proteins. Upon binding of the cytokine to the receptor, receptor chains dimerize. JAKs associated with the receptor tails phosphorylate each other and also phosphorylate the cytoplasmic tails of the receptor chains (phosphates are represented as small green circles). The latter event creates docking sites for STAT proteins. STAT proteins docked with the receptor chains are phosphorylated by the JAKs. Phosphorylated STATs are released from the receptor chains and form STAT dimers, which translocate to the nucleus to mediate transcription of activation genes. One gene activated by the STATs is a member of the negative regulator family of proteins SOCS. Signaling by these receptors is negatively regulated by several mechanisms. One mechanism is binding of SOCS proteins to phosphorylated JAKs and cytokine receptors, which blocks STAT proteins from associating with the receptors. Secondly, the phosphatase SHP-1 (Src homology domain 2-containing phosphatase) can dephosphorylate the cytokine receptors and JAKs, inactivating the receptor complex. Third, the protein inhibitor of activated STATs (PIAS) can bind and inactivate STAT proteins.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.14
Figure 15.14

The IL-1R belongs to the immunoglobulin superfamily of receptors and transduces signal via a mechanism similar to that used by the TLRs. IL-1RAcP participates in signal transduction but does not participate in ligand binding. Binding of IL-1 to IL-1R and IL-1RAcP causes recruitment of the adapter protein MyD88, which allows IRAK to bind to the receptor complex. This initiates a protein phosphorylation cascade culminating in the phosphorylation of the protein IĸB. Phosphorylated IĸB is degraded, liberating the transcriptional activator NF-ĸB, which can then translocate to the nucleus to activate transcription. IKK, IĸB kinase; TAK-1, TGF-β-activated kinase 1.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.15
Figure 15.15

TH cells can be subdivided into two main functional categories: TH1 and TH2. TH1 cells secrete primarily IFN-γ, TNF, and IL-2, promoting cell-mediated immunity, whereas TH2 cells secrete primarily IL-4, IL-5, and IL-10, activating humoral immunity as well as granulocytes such as eosinophils and mast cells. Blue arrows indicate synthesis of soluble mediators.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15.16
Figure 15.16

The two subpopulations of TH cells cross-regulate each other, with TH2 cells negatively regulating TH1-cell development and vice versa. Blue arrows indicate synthesis, green arrows indicate a positive effect, and red lines indicate negative regulation.

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816148.chap15
1. Alexander, W. S. 2002. Suppressors of cytokine signalling (SOCS) in the immune system. Nat. Rev. Immunol. 2:410416.
2. Bodmer, J. L.,, P. Schneider,, and J. Tschopp. 2002. The molecular architecture of the TNF superfamily. Trends Biochem. Sci. 27:1926.
3. Bromley, S. K.,, W. R. Burack,, K. G. Johnson,, K. Somersalo,, T. N. Sims,, C. Sumen,, M. M. Davis,, A. S. Shaw,, P. M. Allen,, and M. L. Dustin. 2001. The immunological synapse. Annu. Rev. Immunol. 19:375396.
4. Colonna, M.,, A. Krug,, and M. Cella. 2002. Interferon-producing cells: on the front line in immune responses against pathogens. Curr. Opin. Immunol. 14:373379.
5. Dinarello, C. A. 2000. Proinflammatory cytokines. Chest 118:503508.
6. Ellery, J. M.,, and P. J. Nicholls. 2002. Alternate signalling pathways from the interleukin-2 receptor. Cytokine Growth Factor Rev. 13:2740.
7. Kisseleva, T.,, S. Bhattacharya,, J. Braunstein,, and C. W. Schindler. 2002. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285:124.
8. Liew, F. Y.,, and I. B. McInnes. 2002. The role of innate mediators in inflammatory responses. Mol. Immunol. 38:887890.
9. Moore, K. W.,, R. de Waal Malefyt,, R. L. Coffman,, and A. O’Garra. 2001. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19:683765.
10. Proudfoot, A. E. 2002. Chemokine receptors: multifaceted therapeutic targets. Nat. Rev. Immunol. 2:106115.
11. Pulendran, B.,, K. Palucka,, and J. Banchereau. 2001. Sensing pathogens and tuning immune responses. Science 293:253256.
12. Robertson, M. J. 2002. Role of chemokines in the biology of natural killer cells. J. Leukoc. Biol. 71:173183.

Tables

Generic image for table
Table 15.1

Chemokine receptors and their ligand specificity

Citation: Tzianabos A, Wetzler L. 2004. Cellular Communication, p 343-370. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch15

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error