Die T-Zell-vermittelte Immunität

Appendices

Aufgaben

1 9.1 Multiple Choice

Welche der folgenden Aussagen trifft zu?

• A. Der Homöoboxtranskriptionsfaktor Prox1 reguliert die Entwicklung des Arterien- und Venensystems.

• B. Arterien setzen Lymphotoxine frei und regen dadurch nichthämatopoetische LTi-Stromazellen zur Entwicklung von Lymphknoten an.

• C. Lymphotoxin-α₃-Signale unterdrücken NFκB, wodurch Cytokine wie CXCL13 exprimiert werden.

• D. Lymphotoxin-α₃ bindet an TNFR1 und unterstützt die Entwicklung der zervikalen und mesenterialen Lymphknoten.

1 9.2 Bitte ergänzen

T- und B-Zellen werden über das Blut auf die sekundären lymphatischen Organe verteilt und dort durch Chemokine in ihre abgegrenzten Kompartimente gelenkt. So wird beispielsweise CCL21 von ________ der T-Zell-Zone in der Milz sezerniert und von den ________ in den Lymphknoten dargeboten. Die Signale dieses Chemokins sowie ________-Signale von CCR7 lenken die T-Zellen in die zugehörige T-Zell-Zone. Andererseits ist ________ der Ligand von CXCR5; er wird sezerniert von ________ und lenkt B-Zellen in die ________. T-Zellen können auch auf CXCL13 reagieren, da eine Subpopulation der T-Zellen ________ exprimiert, die dadurch in B-Zell-Follikel einwandern können und sich an der Bildung von Keimzentren beteiligen.

1 9.3 Multiple Choice

Welche der folgenden Aussagen beschreibt Ereignisse, die notwendig sind, damit naive T-Zellen in die Lymphknoten gelangen können?

• A. CCR7-Signale induzieren Gα, was zu einer verringerten Affinität der Integrinbindung führt.

• B. Die erhöhte Expression des S1P-Rezeptors auf naiven T-Zellen stimuliert deren Wanderung in die Lymphknoten.

• C. Das Entlangrollen an der HEV-Wand bringt T-Zellen in Kontakt mit CCL21, wodurch LFA-1 aktiviert und die Wanderung der Zellen unterstützt wird.

• D. Das auf der HEV-Wand exprimierte MAdCAM-1 interagiert mit CD62L auf der T-Zelle und unterstützt das Einwandern in den Lymphknoten.

1 9.4 Kurze Antwort

In einigen Fällen infizieren Herpes-simplex- oder Influenzaviren antigenpräsentierende Zellen aus den peripheren Geweben, die den naiven T-Zellen keine viralen Antigene präsentieren. Wie kann das Immunsystem gegen solche Krankheitserreger eine adaptive Immunantwort entwickeln?

1 9.5 Richtig oder falsch

Die TLR-Stimulation induziert in den dendritischen Zellen die Expression von CCR7, sodass deren Wanderung durch das Blut zu den Lymphknoten gefördert wird.

1 9.6 Bitte zuordnen

Welche der folgenden Anzeichen für eine Aktivierung bei der Reaktion auf ein Pathogen lässt sich den konventionellen dendritischen Zellen (cDCs) zuordnen, welche den plasmacytoiden dendritischen Zellen (pDCs)?

• A. Produktion von CCL18

• B. ständiges Recycling von MHC-Molekülen nach der Aktivierung

• C. Expression von DC-SIGN

• D. Expression von CD80 und CD86

• E. Expression von CD40L nach Stimulation von TLR-9

1 9.7 Kurze Antwort

Wie unterscheidet sich der Vorgang der Antigenpräsentation bei B-Zellen, dendritischen Zellen und Makrophagen im Zusammenhang mit einer Immunantwort?

1 9.8 Multiple Choice

Welcher der folgenden Effekte tritt bei TCR- und CCR7-Signalen übereinstimmend auf?

• A. Aktivierung von Integrinen

• B. positive Selektion

• C. T_H1-Induktion

• D. T_H2-Induktion

1 9.9 Multiple Choice

Welche der folgenden Beschreibungen trifft auf einen Mechanismus zu, durch den CD28-Signale die IL-2-Produktion steigern können?

• A. CD28-Signale regen die Expression von Proteinen an, die die IL-2-mRNA stabilisieren.

• B. Die PI-3-Kinase hemmt Akt und unterstützt die IL-2-Expression durch Anhalten des Zellzyklus.

• C. Die PI-3-Kinase unterdrückt die Produktion von AP-1 und NFκB, wodurch die IL-2-Produktion erhöht wird.

1 9.10 Richtig oder falsch

Bei den meisten Virusinfektionen ist für die Aktivierung der CD8-T-Zellen eine Unterstützung durch CD4-T-Zellen erforderlich.

1 9.11 Bitte zuordnen

Welches Cytokin von spezifischen Untergruppen der CD4-T-Zellen gehört zu welcher Effektorfunktion?

A.	IL-17	i.	Beseitigung intrazellulärer Infektionen
B.	IL-4	ii.	Reaktion auf extrazelluläre Bakterien
C.	IFN-γ	iii.	Bekämpfung extrazellulärer Parasiten
D.	IL-10	iv.	Unterdrückung von T-Zell-Reaktionen

1 9.12 Bitte zuordnen

Die folgenden Cytokine stimulieren die Effektordifferenzierung der Untergruppen von T_H-Zellen. Welches Cytokin gehört zu welchem untergruppenspezifischen Transkriptionsfaktor?

A.	IFN-γ	i.	RORγt
B.	IL-4	ii.	FoxP3
C.	IL-6 und TGF-β	iii.	T-bet
D.	TGF-β	iv.	GATA3

1 9.13 Multiple Choice

Welche der folgenden Aussagen ist falsch?

• A. Die TCR-Signale sind im cSMAC am stärksten.

• B. Die E3-Ligase C1b vermittelt den Abbau der TCR im cSMAC.

• C. Durch die Umstrukturierung des Cytoskeletts kommt es an der immunologischen Synapse zu einer gezielten Freisetzung von Effektormolekülen.

• D. Integrine wie LFA-1 assoziieren im SMAC.

1 9.14 Bitte ergänzen

Setzen Sie in die einzelnen Leerstellen der folgenden Sätze den jeweils am besten passenden Begriff aus der Liste. Nicht alle Begriffe werden verwendet, aber jeder soll nur einmal vorkommen.

CD8-T-Zellen können spezifisch die Zerstörung von infizierten oder malignen Zellen bewirken. Dafür induzieren CD8-T-Zellen den _______ Zelltod, der auf zwei Weisen ausgelöst werden kann. Einerseits verfügen CD8-T-Zellen über Liganden wie ________, ________ oder ________, die den Apoptoseweg auslösen können. Andererseits kann der Zelltod auch über den intrinsischen Weg ausgelöst werden. Um diesen Mechanismus in Gang zu setzen, werden ________ freigesetzt, sodass Granzyme in die Zelle gelangen können. Sobald sich die Granzyme im Cytoplasma der Zelle befinden, können sie ________ spalten und aktivieren. Diese spaltet dann ________, sodass dieses Enzym die DNA abbauen kann. Granzym B spaltet auch ________, wodurch in der Folge die mitochondriale Membran geschädigt wird, sodass ________ freigesetzt wird und sich das ________ bildet.

CAD	nekrotisch	Caspase 3
intrinsisch	LT-α	Protonengradient
apoptotisch	Caspase 9	ICAD
Apoptosom	extrinsisch	TNF-α
FasL	Perforine	BID
Cytochrom c	Hypoxie

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1.1 Allgemeine Literatur

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1.2 Literatur zu den einzelnen Abschnitten

1.2.1 Abschnitt 9.1.1

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1.2.2 Abschnitt 9.1.2

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1.2.3 Abschnitt 9.1.3

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1.2.4 Abschnitt 9.1.4

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1.2.5 Abschnitt 9.1.5

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• ■ Madri, J.A. and Graesser, D.: Cell migration in the immune system: the evolving interrelated roles of adhesion molecules and proteinases. Dev. Immunol. 2000, 7:103–116.

• ■ Rasmussen, L.K., Johnsen, L.B., Petersen, T.E., and Sørensen, E.S.: Human GlyCAM-1 mRNA is expressed in the mammary gland as splicing variants and encodes various aberrant truncated proteins. Immunol. Lett. 2002, 83:73–75.

• ■ Rosen, S.D.: Ligands for L-selectin: homing, inflammation, and beyond. Annu. Rev. Immunol. 2004, 22:129–156.

• ■ von Andrian, U.H. and Mempel, T.R.: Homing and cellular traffic in lymph nodes. Nat. Rev. Immunol. 2003, 3:867–878.

1.2.6 Abschnitt 9.1.6

• ■ Cyster, J.G.: Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs. Annu. Rev. Immunol. 2005, 23:127–159.

• ■ Laudanna, C., Kim, J.Y., Constantin, G., and Butcher, E.: Rapid leukocyte integrin activation by chemokines. Immunol. Rev. 2002, 186:37–46.

• ■ Lo, C.G., Lu, T.T., and Cyster, J.G.: Integrin-dependence of lymphocyte entry into the splenic white pulp. J. Exp. Med. 2003, 197:353–361.

• ■ Luo, B.H., Carman, C.V., and Springer, T.A.: Structural basis of integrin regulaion and signaling. Annu. Rev. Immunol. 2007, 25:619–647.

• ■ Rosen, H. and Goetzl, E.J.: Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat. Rev. Immunol. 2005, 5:560–570.

1.2.7 Abschnitt 9.1.7

• ■ Cyster, J.G. and Schwab, S.R.: Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs. Annu. Rev. Immunol. 2012, 30:69–94.

1.2.8 Abschnitt 9.1.8

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• ■ Miller, M.J., Wei, S.H., Cahalan, M.D., and Parker, I.: Autonomous T cell traficking examined in vivo with intravital two-photon microscopy. Proc. Natl Acad. Sci. USA 2003, 100:2604–2609.

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• ■ Thery, C. and Amigorena, S.: The cell biology of antigen presentation in dendritic cells. Curr. Opin. Immunol. 2001, 13:45–51.

1.2.9 Abschnitt 9.1.9

• ■ Belz, G.T., Carbone, F.R., and Heath, W.R.: Cross-presentation of antigens by dendritic cells. Crit. Rev. Immunol. 2002, 22:439–448.

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• ■ Mildner, A. and Jung, S.: Development and function of dendritic cells. Immunity 2014, 40:642–656.

• ■ Satpathy, A.T., Wu, X., Albring, J.C., and Murphy, K.M.: Re(de)fining the dendritic cell lineage. Nat. Immunol. 2012, 13:1145–1154.

• ■ Shortman, K. and Heath, W.R.: The CD8⁺ dendritic cell subset. Immunol. Rev. 2010, 234:18–31.

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1.2.10 Abschnitt 9.1.10

• ■ Allan, R.S., Waithman, J., Bedoui, S., Jones, C.M., Villadangos, J.A., Zhan, Y., Lew, A.M., Shortman, K., Heath, W.R., and Carbone, F.R.: Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity 2006, 25:153–162.

• ■ Bachman, M.F., Kopf, M., and Marsland, B.J.: Chemokines: more than just road signs. Nat. Rev. Immunol. 2006, 6:159–164.

• ■ Blander, J.M. and Medzhitov, R.: Toll-dependent selection of microbial anti-gens for presentation by dendritic cells. Nature 2006, 440:808–812.

• ■ Iwasaki, A. and Medzhitov, R.: Toll-like receptor control of adaptive immune responses. Nat. Immunol. 2004, 10:988–995.

• ■ Reis e Sousa, C.: Toll-like receptors and dendritic cells: for whom the bug tolls. Semin. Immunol. 2004, 16:27–34.

1.2.11 Abschnitt 9.1.11

• ■ Asselin-Paturel, C. and Trinchieri, G.: Production of type I interferons: plasmacytoid dendritic cells and beyond. J. Exp. Med. 2005, 202:461–465.

• ■ Krug, A., Veeraswamy, R., Pekosz, A., Kanagawa, O., Unanue, E.R., Colonna, M., and Cella, M.: Interferon-producing cells fail to induce proliferation of naïve T cells but can promote expansion and T helper 1 differentiation of antigen-experienced unpolarized T cells. J. Exp. Med. 2003, 197:899–906.

• ■ Kuwajima, S., Sato, T., Ishida, K., Tada, H., Tezuka, H., and Ohteki, T.: Interleukin 15-dependent crosstalk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation. Nat. Immunol. 2006, 7:740–746.

• ■ Swiecki, M. and Colonna, M.: Unraveling the functions of plasmacytoid dendritic cells during viral infections, autoimmunity, and tolerance. Immunol. Rev. 2010, 234:142–162.

1.2.12 Abschnitt 9.1.12

• ■ Barker, R.N., Erwig, L.P., Hill, K.S., Devine, A., Pearce, W.P., and Rees, A.J.: Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells. Clin. Exp. Immunol. 2002, 127:220–225.

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• ■ Zhu, F.G., Reich, C.F., and Pisetsky, D.S.: The role of the macrophage scavenger receptor in immune stimulation by bacterial DNA and synthetic oligonucleotides. Immunology 2001, 103:226–234.

1.2.13 Abschnitt 9.1.13

• ■ Guermonprez, P., England, P., Bedouelle, H., and Leclerc, C.: The rate of dissociation between antibody and antigen determines the efficiency of antibody-mediated antigen presentation to T cells. J. Immunol. 1998, 161:4542–4548.

• ■ Shirota, H., Sano, K., Hirasawa, N., Terui, T., Ohuchi, K., Hattori, T., and Tamura, G.: B cells capturing antigen conjugated with CpG oligodeoxynucleotides induce Th1 cells by elaborating IL-12. J. Immunol. 2002, 169:787–794.

• ■ Zaliauskiene, L., Kang, S., Sparks, K., Zinn, K.R., Schwiebert, L.M., Weaver, C.T., and Collawn, J.F.: Enhancement of MHC class II-restricted responses by receptor-mediated uptake of peptide antigens. J. Immunol. 2002, 169:2337–2345.

1.2.14 Abschnitt 9.2.1

• ■ Dustin, M.L.: T-cell activation through immunological synapses and kinapses. Immunol. Rev. 2008, 221:77–89.

• ■ Friedl, P. and Brocker, E.B.: TCR triggering on the move: diversity of T-cell interactions with antigen-presenting cells. Immunol. Rev. 2002, 186:83–89.

• ■ Gunzer, M., Schafer, A., Borgmann, S., Grabbe, S., Zanker, K.S., Brocker, E.B., Kampgen, E., and Friedl, P.: Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential. Immunity 2000, 13:323–332.

• ■ Montoya, M.C., Sancho, D., Vicente-Manzanares, M., and Sanchez-Madrid, F.: Cell adhesion and polarity during immune interactions. Immunol. Rev. 2002, 186:68–82.

• ■ Wang, J. and Eck, M.J.: Assembling atomic resolution views of the immunological synapse. Curr. Opin. Immunol. 2003, 15:286–293.

1.2.15 Abschnitt 9.2.2

• ■ Bour-Jordan, H. and Bluestone, J.A.: CD28 function: a balance of costimulatory and regulatory signals. J. Clin. Immunol. 2002, 22:1–7.

• ■ Chen, L. and Flies, D.B.: Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat. Rev. Immunol. 2013, 13:227–242.

• ■ Gonzalo, J.A., Delaney, T., Corcoran, J., Goodearl, A., Gutierrez-Ramos, J.C., and Coyle, A.J.: Cutting edge: the related molecules CD28 and inducible costimulator deliver both unique and complementary signals required for optimal T-cell activation. J. Immunol. 2001, 166:1–5.

• ■ Greenwald, R.J., Freeman, G.J., and Sharpe, A.H.: The B7 family revisited. Annu. Rev. Immunol. 2005, 23:515–548.

• ■ Kapsenberg, M.L.: Dendritic-cell control of pathogen-driven T-cell polarization. Nat. Rev. Immunol. 2003, 3:984–993.

• ■ Wang, S., Zhu, G., Chapoval, A.I., Dong, H., Tamada, K., Ni, J., and Chen, L.: Costimulation of T cells by B7-H2, a B7-like molecule that binds ICOS. Blood 2000, 96:2808–2813.

1.2.16 Abschnitt 9.2.3

• ■ Acuto, O. and Michel, F.: CD28-mediated co-stimulation: a quantitative support for TCR signalling. Nat. Rev. Immunol. 2003, 3:939–951.

• ■ Gaffen, S.L.: Signaling domains of the interleukin 2 receptor. Cytokine 2001, 14:63–77.

• ■ Seko, Y., Cole, S., Kasprzak, W., Shapiro, B.A., and Ragheb, J.A.: The role of cytokine mRNA stability in the pathogenesis of autoimmune disease. Autoimmun. Rev. 2006, 5:299–305.

• ■ Zhou, X.Y., Yashiro-Ohtani, Y., Nakahira, M., Park, W.R., Abe, R., Hamaoka, T., Naramura, M., Gu, H., and Fujiwara, H.: Molecular mechanisms underlying differential contribution of CD28 versus non-CD28 costimulatory molecules to IL-2 promoter activation. J. Immunol. 2002, 168:3847–3854.

1.2.17 Abschnitt 9.2.4

• ■ Croft, M.: The role of TNF superfamily members in T-cell function and diseases. Nat. Rev. Immunol. 2009, 9:271–285.

• ■ Greenwald, R.J., Freeman, G.J., and Sharpe, A.H.: The B7 family revisited. Annu. Rev. Immunol. 2005, 23:515–548.

• ■ Watts, T.H.: TNF/TNFR family members in costimulation of T cell responses. Annu. Rev. Immunol. 2005, 23:23–68.

1.2.18 Abschnitt 9.2.5

• ■ Gudmundsdottir, H., Wells, A.D., and Turka, L.A.: Dynamics and requirements of T cell clonal expansion in vivo at the single-cell level: effector function is linked to proliferative capacity. J. Immunol. 1999, 162:5212–5223.

• ■ London, C.A., Lodge, M.P., and Abbas, A.K.: Functional responses and costimulator dependence of memory CD4+ T cells. J. Immunol. 2000, 164:265–272.

• ■ Schweitzer, A.N. and Sharpe, A.H.: Studies using antigen-presenting cells lacking expression of both B7-1 (CD80) and B7-2 (CD86) show distinct requirements for B7 molecules during priming versus restimulation of Th2 but not Th1 cytokine production. J. Immunol. 1998, 161:2762–2771.

1.2.19 Abschnitt 9.2.6

• ■ Andreasen, S.O., Christensen, J.E., Marker, O., and Thomsen, A.R.: Role of CD40 ligand and CD28 in induction and maintenance of antiviral CD8⁺ effector T cell responses. J. Immunol. 2000, 164:3689–3697.

• ■ Blazevic, V., Trubey, C.M., and Shearer, G.M.: Analysis of the costimulatory requirements for generating human virus-specific in vitro T helper and effector responses. J. Clin. Immunol. 2001, 21:293–302.

• ■ Liang, L. and Sha, W.C.: The right place at the right time: novel B7 family members regulate effector T cell responses. Curr. Opin. Immunol. 2002, 14:384–390.

• ■ Seder, R.A. and Ahmed, R.: Similarities and differences in CD4⁺ and CD8⁺ effector and memory T cell generation. Nat. Immunol. 2003, 4:835–842.

• ■ Weninger, W., Manjunath, N., and von Andrian, U.H.: Migration and differentiation of CD8⁺ T cells. Immunol. Rev. 2002, 186:221–233.

1.2.20 Abschnitt 9.2.7

• ■ Basu, R., Hatton, R.D., and Weaver, C.T.: The Th17 family: flexibility follows function. Immunol. Rev. 2013, 252:89–103.

• ■ Bluestone, J.A. and Abbas, A.K.: Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 2003, 3:253–257.

• ■ Crotty, S.: Follicular helper T cells (T_FH). Annu. Rev. Immunol. 2011, 29:621–663.

• ■ King, C.: New insights into the differentiation and function of T follicular helper cells. Nat. Rev. Immunol. 2009, 9:757–766.

• ■ Littman, D.R. and Rudensky, A.Y.: Th17 and regulatory T cells in mediating and restraining inflammation. Cell 2010, 140:845–858.

• ■ Murphy, K.M., and Reiner, S.L.: The lineage decisions of helper T cells. Nat. Rev. Immunol. 2002, 2:933–944.

• ■ Nurieva, R.I. and Chung, Y.: Understanding the development and function of T follicular helper cells. Cell Mol. Immunol. 2010, 7:190–197.

1.2.21 Abschnitt 9.2.8

• ■ Nath, I., Vemuri, N., Reddi, A.L., Jain, S., Brooks, P., Colston, M.J., Misra, R.S., and Ramesh, V.: The effect of antigen presenting cells on the cytokine profiles of stable and reactional lepromatous leprosy patients. Immunol. Lett. 2000, 75:69–76.

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1.2.22 Abschnitt 9.2.9

• ■ Croft, M., Carter, L., Swain, S.L., and Dutton, R.W.: Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles. J. Exp. Med. 1994, 180:1715–1728.

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1.2.23 Abschnitt 9.2.10

• ■ Fontenot, J.D. and Rudensky, A.Y.: A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat. Immunol. 2005, 6:331–337.

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• ■ Saraiva, M. and O’Garra, A.: The regulation of IL-10 production by immune cells. Nat. Rev. Immunol. 2010, 10:170–181.

1.2.24 Abschnitt 9.3.1

• ■ Dustin, M.L.: T-cell activation through immunological synapses and kinases. Immunol. Rev. 2008, 221:77–89.

• ■ van der Merwe, P.A. and Davis, S.J.: Molecular interactions mediating T cell antigen recognition. Annu. Rev. Immunol. 2003, 21:659–684.

1.2.25 Abschnitt 9.3.2

• ■ Bossi, G., Trambas, C., Booth, S., Clark, R., Stinchcombe, J., and Griffiths, G.M.: The secretory synapse: the secrets of a serial killer. Immunol. Rev. 2002, 189:152–160.

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• ■ Trambas, C.M. and Griffiths, G.M.: Delivering the kiss of death. Nat. Immunol. 2003, 4:399–403.

1.2.26 Abschnitte 9.3.3 und 9.3.4

• ■ Basler, C.F. and Garcia-Sastre, A.: Viruses and the type I interferon antiviral system: induction and evasion. Int. Rev. Immunol. 2002, 21:305–337.

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• ■ Proudfoot, A.E.: Chemokine receptors: multifaceted therapeutic targets. Nat. Rev. Immunol. 2002, 2:106–115.

1.2.27 Abschnitt 9.3.5

• ■ Bekker, L.G., Freeman, S., Murray, P.J., Ryffel, B., and Kaplan, G.: TNF-alpha controls intracellular mycobacterial growth by both inducible nitric oxide synthase-dependent and inducible nitric oxide synthase-independent pathways. J. Immunol. 2001, 166:6728–6734.

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1.2.28 Abschnitt 9.4.1

• ■ Aggarwal, B.B.: Signalling pathways of the TNF superfamily: a double-edged sword. Nat. Rev. Immunol. 2003, 3:745–756.

• ■ Ashton-Rickardt, P.G.: The granule pathway of programmed cell death. Crit Rev. Immunol. 2005, 25:161–182.

• ■ Bishop, G.A.: The multifaceted roles of TRAFs in the regulation of B-cell function. Nat. Rev. Immunol. 2004, 4:775–786.

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• ■ Siegel, R.M.: Caspases at the crossroads of immune-cell life and death. Nat. Rev. Immunol. 2006, 6:308–317.

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1.2.29 Abschnitt 9.4.2

• ■ Borner, C.: The Bcl-2 protein family: sensors and checkpoints for life-or- death decisions. Mol. Immunol. 2003, 39:615–647.

• ■ Bratton, S.B. and Salvesen, G.S.: Regulation of the Apaf-1-caspase-9 apoptosome. J. Cell Sci. 2010, 123:3209–3214.

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• ■ Strasser, A.: The role of BH3-only proteins in the immune system. Nat. Rev. Immunol. 2005, 5:189–200.

1.2.30 Abschnitt 9.4.3

• ■ Barry, M., Heibein, J.A., Pinkoski, M.J., Lee, S.F., Moyer, R.W., Green, D.R., and Bleackley, R.C.: Granzyme B short-circuits the need for caspase 8 activity during granule-mediated cytotoxic T-lymphocyte killing by directly cleaving Bid. Mol. Cell Biol. 2000, 20:3781–3794.

• ■ Grossman, W.J., Revell, P.A., Lu, Z.H., Johnson, H., Bredemeyer, A.J., and Ley, T.J.: The orphan granzymes of humans and mice. Curr. Opin. Immunol. 2003, 15:544–552.

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• ■ Pipkin, M. E. and Lieberman, J.: Delivering the kiss of death: progress on understanding how perforin works. Curr. Opin. Immunol. 2007, 19:301–308.

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1.2.31 Abschnitt 9.4.4

• ■ Stinchcombe, J.C. and Griffiths, G.M.: Secretory mechanisms in cell-mediated cytotoxicity. Annu. Rev. Cell Dev. Biol. 2007, 23:495–517.

• ■ Veugelers, K., Motyka, B., Frantz, C., Shostak, I., Sawchuk, T., and Bleackley, R.C.: The granzyme B-serglycin complex from cytotoxic granules requires dynamin for endocytosis. Blood 2004, 103:3845–3853.

1.2.32 Abschnitt 9.4.5

• ■ Amel-Kashipaz, M.R., Huggins, M.L., Lanyon, P., Robins, A., Todd, I., and Powell, R.J.: Quantitative and qualitative analysis of the balance between type 1 and type 2 cytokine-producing CD8⁻ and CD8⁺ T cells in systemic lupus erythematosus. J. Autoimmun. 2001, 17:155–163.

• ■ Dobrzanski, M.J., Reome, J.B., Hollenbaugh, J.A., and Dutton, R.W.: Tc1 and Tc2 effector cell therapy elicit long-term tumor immunity by contrasting mechanisms that result in complementary endogenous type 1 antitumor responses. J. Immunol. 2004, 172:1380–1390.

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