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Molecular Immunology

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Immunologia Molecolare

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Academic year 2016/2017

Course ID
BIO0114
Teacher
Prof. Federica CAVALLO
Year
1st year
Type
Distinctive
Credits/Recognition
5
Course disciplinary sector (SSD)
MED/04 - patologia generale
Delivery
Formal authority
Language
English
Attendance
Obligatory
Type of examination
Written and oral
Prerequisites

Having a solid background in genetics, molecular biology and basic immunology; possibility to attend lessons on an ongoing basis


Possedere una solida preparazione in genetica, biologia molecolare e immunologia di base; possibilità di presenziare alle lezioni in modo continuativo.

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Sommario del corso

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Course objectives

The course does provide students with:

  • the tools to interpret the molecular mechanisms of the natural and adaptive immune response and of the pathogenesis of diseases in which the immune system is involved;
  • an advanced biotechnological up-dating about the main immunological techniques used in the laboratory practice;
  • the competencies to presenting to the audience a scientific concept and discussing it

L’insegnamento vuol fornire allo studente:

  • gli strumenti per interpretare i meccanismi molecolari della risposta immunitaria naturale e adattativa e della patogenesi delle malattie nelle quali il sistema immunitario è coinvolto;
  • un aggiornamento biotecnologico avanzato riguardo le principali tecniche immunologiche utilizzate nella pratica di laboratorio;
  • le competenze per presentare al pubblico un concetto scientifico e discuterne. 
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Results of learning outcomes

The student who has followed the course will have understood the main molecular mechanisms by which the immune system contributes to the prevention, healing and sometimes the development of diseases. The student will also have acquired the methodological tools to understand and apply the main immunological techniques used in laboratory practice and to present and discuss a scientific concept.

Lo studente che abbia seguito l'insegnamento avrà compreso i principali meccanismi molecolari attraverso i quali il sistema immunitario contribuisce alla prevenzione, guarigione e talvolta sviluppo delle patologie. Lo studente avrà inoltre acquisito gli strumenti metodologici per comprendere ed applicare le principali tecniche immunologiche utilizzate nella pratica di laboratorio e presentare e discutere un concetto scientifico. 

 

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Course delivery

The course consists of lectures, which include the oral presentations of each student, and subsequent open discussion. At the beginning of the course there is an entry test to determine whether students have the prerequisites (knowledge of basic immunology, genetics and molecular biology) to follow the course. Support is offered individually or in small groups outside lesson for those that demonstrate weaknesses in the prerequisites

L’insegnamento si articola in lezioni frontali, comprendenti le presentazioni orali di ciascuno studente, e successiva discussione aperta. All’inizio delle lezioni è previsto un test di ingresso per valutare se gli studenti hanno i prerequisiti (conoscenze di immunologia di base, genetica e biologica molecolare) necessari per seguire l’insegnamento. 

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Learning assessment methods

The course grade determination consists in the evaluation of three aspects:

1. Check “in itinere” the level of student attention/participation: During the lessons the students respond in writing to easy questions on the fundamental aspects of the topics covered in the previous lesson. For each correct answer is assigned a point; the questions are in total 30.

2. Verification of the capacity to present and critically analyse a scientific concept: each student presents, in 20-30 minutes, a topic of the program and discusses it by answering questions from the teacher and the other students. The teacher assigns a mark in grades from 1 to 30 on the basis of:

  • Quality of information and bibliographic references supplied
  • Clarity of the document (slides)
  • Oral skill in communicating the message (presentation should be in English)
  • Ability to use the time given correctly
  • General comment given by classmates

3. Final assessment of learning: at the end of the course students take a test with multiple-choice questions. It is given a mark in grades form 1 to 30.

The final grade will be the arithmetic mean of these three marks.

La modalità di verifica dell’apprendimento consta nella valutazione di tre aspetti:

1. Verifica in itinere del livello di attenzione/partecipazione degli studenti: durante le lezioni gli studenti rispondono per iscritto a facili domande sugli aspetti fondamentali degli argomenti trattati nella lezione precedente. Per ogni risposta esatta viene assegnato un punto; le domande sono in totale 30.

2. Verifica della capacità espositiva e di analisi critica di un concetto scientifico: ciascuno studente presenta in 20-30 minuti un argomento del programma e lo discute rispondendo alle domande dei colleghi e dell’insegnante. Al termine dell’esposizione l’insegnante assegna un punteggio in trentesimi sulla base di:

  • Qualità delle informazioni fornite e relative referenze bibliografiche
  • Chiarezza del documento (diapositive presentate)
  • Abilità nel comunicare il messaggio (la presentazione dovrebbe essere fatta in inglese)
  • Utilizzo corretto del tempo a disposizione
  • Giudizio generale dato dagli altri studenti.

3. Verifica finale dell’apprendimento: alla fine dell’insegnamento gli studenti sostengono un test con domande a risposta multipla. Viene assegnato un voto in trentesimi. 

Il voto finale sarà la media matematica di questi tre voti. 

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Support activities

For those that in the entry test show deficiencies in the prerequisites, support is offered individually or in small groups outside lesson.

Per chi nel test di ingresso dimostrasse delle carenze nei prerequisiti, viene offerta assistenza individuale o a piccoli gruppi fuori dall’orario di lezione.

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Program

  • Signalling pathways downstream of the receptors of the innate immune response; inflammasomes and autophagosomes
  • Signal transduction downstream of type I and II cytokine receptors
  • Molecular mechanisms of the V(D)J recombination and central tolerance
  • Signalling pathways downstream of the antigen receptors of T and B cells; costimulatory receptors and immune checkpoints
  • Molecular mechanisms of antigen presentation on MHC class I and II molecules; the enhanceosomes of the MHC molecules
  • Molecular mechanisms of somatic hypermutation and class-switch recombination
  • Molecular mechanisms of the hypersensitivities
  • The detection, measurement, and characterization of antibodies and their use as research and diagnostic tools
  • Isolation of lymphocytes and characterization of their specificity, frequency and function
  • Detection of immunity in vivo

  • Le vie di segnalazione a valle dei recettori della risposta innata; inflammasoni e autofagosomi
  • La trasduzione del segnale a valle dei recettori delle citochine di tipo I e II
  • Meccanismi molecolari della ricombinazione V(D)J e della tolleranza centrale
  • Le vie di segnalazione a valle dei recettori per l’antigene dei linfociti T e dei linfociti B; recettori di costimolazione e chekpoints immunitari
  • Meccanismi molecolari della presentazione degli antigeni sulle molecole MHC di classe I e di classe II; gli enhansosomi delle molecole MHC
  • Meccanismi molecolari della ipermutazione somatica e della commutazione di classe
  • Meccanismi molecolari delle ipersensibilità
  • Rilevamento, misurazione e caratterizzazione degli anticorpi, e loro uso nella terapia e nella diagnostica
  • Isolamento dei linfociti e caratterizzazione della loro specificità, frequenza e funzione.
  • La determinazione dell’immunità in vivo. 

Suggested readings and bibliography

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  1. Janeway’s Immunobiology, Eighth edition, K Murphy, Garland Science
  2. Cellular and Molecular Immunology, Sixth Edition, AK Abbas et al., Elsevier Saunders
  3. The Immune System, Fourth Edition, P Parham, Garland Science

Updated reviews (mainly from Nature Reviews Immunology) on topics to be covered in class will be uploaded on CampusNet before the beginning of the course.

  1. Janeway’s Immunobiology, Eighth edition, K Murphy, Garland Science
  2. Cellular and Molecular Immunology, Sixth Edition, AK Abbas et al., Elsevier Saunders
  3. The Immune System, Fourth Edition, P Parham, Garland Science

Prima dell’inizio delle lezioni verranno caricate su CampusNet delle review aggiornate (principalmente da Nature Reviews Immunology) riguardo gli argomenti che verranno trattati durante le lezioni. 

 



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Note

T lymphocytes and the T Cell Receptor (TCR):

- Toor AA, Toor AA, Rahmani M, Manjili MH. On the organization of human T-cell receptor loci: log-periodic distribution of T-cell receptor gene segments. J R Soc Interface. 2016 Jan;13(114).

- Crotty S. A brief history of T cell help to B cells. Nat Rev Immunol. 2015 Mar;15(3):185-9.

- Hoeppli RE, Wu D, Cook L, Levings MK. The environment of regulatory T cell biology: cytokines, metabolites, and the microbiome. Front Immunol. 2015 Feb 18;6:61.

- Istomine R, Pavey N, Piccirillo CA. Posttranscriptional and Translational Control of Gene Regulation in CD4+ T Cell Subsets. J Immunol. 2016 Jan 15;196(2):533-40.

- Zhang Q, Lakkis FG. Memory T Cell Migration. Front Immunol. 2015 Oct 2;6:504.

- Yui MA, Rothenberg EV. Developmental gene networks: a triathlon on the course to T cell identity. Nat Rev Immunol. 2014 Aug;14(8):529-45.

- Shimazaki N, Lieber MR. Histone methylation and V(D)J recombination. Int J Hematol. 2014 Sep;100(3):230-7.

- Matthews AG, Oettinger MA. RAG: a recombinase diversified.Nat Immunol. 2009 Aug;10(8):817-21.

- Fugmann SD. The origins of the Rag genes--from transposition to V(D)J recombination. Semin Immunol. 2010 Feb;22(1):10-6.

Antigen recognition by the T lymphocytes and their activation:

- Seddon B. Thymic IL-7 signaling goes beyond survival. Nat Immunol. 2015 Apr;16(4):337-8.

- Roche PA, Furuta K. The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol. 2015 Apr;15(4):203-16.

- Skogberg G, Telemo E, Ekwall O. Exosomes in the Thymus: Antigen Transfer and Vesicles. Front Immunol. 2015 Jul 20;6:366.

- Klein L, Kyewski B, Allen PM, Hogquist KA. Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat Rev Immunol. 2014 Jun;14(6):377-91.

- van der Merwe PA, Dushek O. Mechanisms for T cell receptor triggering.Nat Rev Immunol. 2011 Jan;11(1):47-55.

- Sim GC, Radvanyi L The IL-2 cytokine family in cancer immunotherapy.Nature Reviews Immunology 15, 283–294. Reviews |17 April 2015.

- Kobayashi KS, van den Elsen PJ. NLRC5: a key regulator of MHC class I-dependent immune responses. Nat Rev Immunol. 2012 Dec;12(12):813-20.

-  Neefjes J, Jongsma ML, Paul P, Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol. 2011 Nov 11;11(12):823-36.

-  Groettrup M, Kirk CJ, Basler M. Proteasomes in immune cells: more than peptide producers? Nat Rev Immunol. 2010 Jan;10(1):73-8.

-  Joffre OP, Segura E, Savina A, Amigorena S. Cross-presentation by dendritic cells. Nat Rev Immunol. 2012 Jul 13;12(8):557-69.

Lymphoid Organs:

-  Boehm T, Swann JB. Thymus involution and regeneration: two sides of the same coin? Nat Rev Immunol. 2013 Nov;13(11):831-8.

-  Miller JF. The golden anniversary of the thymus. Nat Rev Immunol. 2011 May 27;11(7):489-95.

- Claman HN. On discovering thymus-marrow synergism. Front Immunol. 2014 Nov 21;5:588.

- Crystal L. Mackall, Terry J. Fry & Ronald E. Gress. Harnessing the biology of IL-7 for therapeutic application. Nature Reviews Immunology 11, 330–342 Reviews 21 April 2011.

- Yvonne Bordon. Cytokines: T cells take a break from IL-7.Nature Reviews Immunology 13, 70–71. Research Highlights 21 January 2013.

- Radtke F, MacDonald HR, Tacchini-Cottier F. Regulation of innate and adaptive immunity by Notch. Nat Rev Immunol. 2013 Jun;13(6):427-37.

- Amsen D, Antov A, Flavell RA. The different faces of Notch in T-helper-cell differentiation. Nat Rev Immunol. 2009 Feb;9(2):116-24.

- Love PE, Bhandoola A. Signal integration and crosstalk during thymocyte migration and emigration. Nat Rev Immunol. 2011 Jun 24;11(7):469-77.

- Koch U, Fiorini E, Benedito R, Besseyrias V, Schuster-Gossler K, Pierres M, Manley NR, Duarte A, Macdonald HR, Radtke F. Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment. J Exp Med. 2008 Oct 27;205(11):2515-23.

- Mackall CL, Fry TJ, Gress RE. Harnessing the biology of IL-7 for therapeutic application. Nat Rev Immunol. 2011 May;11(5):330-42.

The Thymus: Cortex:

- Mark D Bunting, Iain Comerford and Shaun R McColl Finding their niche: chemokines directing cell migration in the thymus. Immunology and Cell Biology (2011) 89, 185–196.

- Paul E. Love & Avinash BhandoolaSignal integration and crosstalk during thymocyte migration and emigration. Nature Reviews Immunology 11, 469-477 (July 2011).

- Ribatti D. The discovery of the blood-thymus barrier. Immunol Lett. 2015 Dec;168(2):325-8.

- Hamazaki Y. Adult thymic epithelial cell (TEC) progenitors and TEC stem cells: Models and mechanisms for TEC development and maintenance. Eur J Immunol. 2015 Nov;45(11):2985-93.

- Hu Z, Lancaster JN, Ehrlich LI. The Contribution of Chemokines and Migration to the Induction of Central Tolerance in the Thymus. Front Immunol. 2015 Aug 7;6:398.

- Passos GA, Mendes-da-Cruz DA, Oliveira EH. The Thymic Orchestration Involving Aire, miRNAs, and Cell-Cell Interactions during the Induction of Central Tolerance. Front Immunol. 2015 Jul 14;6:352.

- Halkias J, Melichar HJ, Taylor KT, Robey EA. Tracking migration during human T cell development. Cell Mol Life Sci. 2014 Aug;71(16):3101-17.

The Thymus: Medulla:

- Cowan JE, Jenkinson WE, Anderson G. Thymus medulla fosters generation of natural Treg cells, invariant γδ T cells, and invariant NKT cells: what we learn from intrathymic migration. Eur J Immunol. 2015 Mar;45(3):652-60.

- Thiault N, Darrigues J, Adoue V, Gros M, Binet B, Perals C, Leobon B, Fazilleau N, Joffre OP, Robey EA, van Meerwijk JP, Romagnoli P. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat Immunol. 2015 Jun;16(6):628-34.

- Hsieh CS, Lee HM, Lio CW. Selection of regulatory T cells in the thymus. Nat Rev Immunol. 2012 Feb 10;12(3):157-67.

- Lopes N, Sergé A, Ferrier P, Irla M. Thymic Crosstalk Coordinates Medulla Organization and T-Cell Tolerance Induction. Front Immunol. 2015 Jul 20;6:365.

- Alves NL, Takahama Y, Ohigashi I, Ribeiro AR, Baik S, Anderson G, Jenkinson WE. Serial progression of cortical and medullary thymic epithelial microenvironments. Eur J Immunol. 2014 Jan;44(1):16-22.

- Laan M, Peterson P. The many faces of aire in central tolerance. Front Immunol. 2013 Oct 11;4:326.

- Nitta T, Ohigashi I, Nakagawa Y, Takahama Y. Cytokine crosstalk for thymic medulla formation. Curr Opin Immunol. 2011 Apr;23(2):190-7.

Tolerance:

- Richards DM, Kyewski B, Feuerer M. Re-examining the Nature and Function of Self-Reactive T cells. Trends Immunol. 2016 Feb;37(2):114-25.

- Sack BK, Herzog RW, Terhorst C, Markusic DM. Development of Gene Transfer for Induction of Antigen-specific Tolerance. Mol Ther Methods Clin Dev. 2014 Apr 30;1:14013.

- Ucar O, Rattay K. Promiscuous Gene Expression in the Thymus: A Matter of Epigenetics, miRNA, and More? Front Immunol. 2015 Mar 3;6:93.

- Chuprin A, Avin A, Goldfarb Y, Herzig Y, Levi B, Jacob A, Sela A, Katz S, Grossman M, Guyon C, Rathaus M, Cohen HY, Sagi I, Giraud M, McBurney MW, Husebye ES, Abramson J. The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance. Nat Immunol. 2015 Jul;16(7):737-45.

- Leavy O. B cells: Mediators of central tolerance. Nat Rev Immunol. 2015 Jul;15(7):404.

- Anderson G, Lane PJ, Jenkinson EJ. Generating intrathymic microenvironments to establish T-cell tolerance. Nat Rev Immunol. 2007 Dec;7(12):954-63.

- Yui MA, Rothenberg EV. Developmental gene networks: a triathlon on the course to T cell identity. Nat Rev Immunol. 2014 Aug;14(8):529-45.

- Boehm T, Swann JB. Thymus involution and regeneration: two sides of the same coin? Nat Rev Immunol. 2013 Nov;13(11):831-8.

- Klein L, Kyewski B, Allen PM, Hogquist KA. Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat Rev Immunol. 2014 Jun;14(6):377-91.

- Klein L, Hinterberger M, Wirnsberger G, Kyewski B. Antigen presentation in the thymus for positive selection and central tolerance induction. Nat Rev Immunol. 2009 Dec;9(12):833-44.

- Singer A, Adoro S, Park JH. Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice. Nat Rev Immunol. 2008 Oct;8(10):788-801.

- Palmer E, Naeher D. Affinity threshold for thymic selection through a T-cell receptor-co-receptor zipper. Nat Rev Immunol. 2009 Mar;9(3):207-13.

- Groettrup M, Kirk CJ, Basler M. Proteasomes in immune cells: more than peptide producers? Nat Rev Immunol. 2010 Jan;10(1):73-8.

- Hsieh CS, Lee HM, Lio CW. Selection of regulatory T cells in the thymus. Nat Rev Immunol. 2012 Feb 10;12(3):157-67.

Thymus in Diseases:

- de Jong M, Essers J, van Weerden WM. Imaging preclinical tumour models: improving translational power. Nat Rev Cancer. 2014 Jul;14(7):481-93.

- Liew PX, Kubes P. Intravital imaging - dynamic insights into natural killer T cell biology. Front Immunol. 2015 May 20;6:240.

- Priola AM, Galetto G, Priola SM. Diagnostic and functional imaging of thymic and mediastinal involvement in lymphoproliferative disorders. Clin Imaging. 2014 Nov-Dec;38(6):771-84.

- Walkovich K, Connelly JA. Primary immunodeficiency in the neonate: Early diagnosis and management. Semin Fetal Neonatal Med. 2016 Feb;21(1):35-43.

- Shahar Shelly, Nancy Agmon-Levin, Arie Altman and Yehuda Shoenfeld. Thymoma and autoimmunity. Cellular & Molecular Immunology (2011) 8, 199–202.

- Katoh H, Zheng P, Liu Y. FOXP3: genetic and epigenetic implications for autoimmunity. J Autoimmun. 2013 Mar;41:72-8.

- Shimon Sakaguchi, Fiona Powrie & Richard M Ransohoff Re-establishing immunological self-tolerance in autoimmune disease. Nat. Med. 18, 54–58 Comments and Opinion 06 January 2012.

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