CORSO DI IMMUNOLOGIA per il corso di Laurea in biotecnologie a.a. 2005-2006 II semestre

1. CORSO DI IMMUNOLOGIAper il corso di Laurea in biotecnologiea.a. 2005-2006 II semestre DOCENTE: Dott.ssa Vladia Monsurrò Dipartimento di patologia Sezione di immunologia Universita’ degli Studi di Verona 045 8074256 vladia.monsurro@univr.it ORARIO DELLE LEZIONI: lunedì: 4:30-6:00 giovedì 4:30-6:00 dal 20 marzo al 25 maggio 2006 aula F Facolta’ di Scienze

2. CONSIGLIATI: A. K. ABBAS, A.H. LICHTMAN Fondamenti di Immunologia. Funzioni e Alterazioni del Sistema Immunitario. Ed. PICCIN Nuova Libraria S.p.A. – Padova, 2003 (Euro 25.00) DI CONSULTAZIONE: A.K. ABBAS, A. H. LICHTMAN, J.S. POBER Immunologia cellulare e molecolare, quarta edizione, PICCIN Nuova Libraria S.p.A., Padova, 2002 (Euro. 50) Cellular and Molecular Immunology, Updated Edition, 5th edition with STUDENT CONSULT Access, Saunders, March 2005 (Euro 69.00) DI APPROFONDIMENTO: WILLIAM E.PAUL Fundamental Immunology fifth edition, Lippincott, Williams & Wilkins, Philadelphia, PA USA, 2003 TESTI

3. PROGRAMMA LEZIONI

5. IMMUNITA’ ACQUISITA IMMUNITA’ INNATA Innate and adaptive immunity. The mechanisms of innate immunity provide the initial defense against infections. Adaptive immune responses develop later and consist of activation of lymphocytes. The kinetics of the innate and adaptive immune responses are approximations and may vary in different infections

6. IMMUNITA’ UMORALE IMMUNITA’ CELLULO/MEDIATA Types of adaptive immunity. In humoral immunity, B lymphocytes secrete antibodies that prevent infections by and eliminate extracellular microbes. In cell-mediated immunity, T lymphocytes either activate macrophages to kill phagocytosed microbes or cytolytic T lymphocytes directly destroy infected cells.

7. Specificity, memory, and self-limitation of immune responses. Antigens X and Y induce the production of different antibodies (specificity). The secondary response to antigen X is more rapid and larger than the primary response (memory). Antibody levels decline with time after each immunization (self-limitation).The same features are seen in cell-mediated immune responses

8. Phases of adaptive immune responses. Adaptive immune responses consist of distinct phases, the first three being the recognition of antigen, the activation of lymphocytes, and the effector phase (elimination of antigen). The response declines as antigen-stimulated lymphocytes die by apoptosis, and the antigen-specific cells that survive are responsible for memory. The duration of each phase may vary in different immune responses. The y-axis represents an arbitrary measure of the magnitude of the response. These principles apply to humoral immunity (mediated by B lymphocytes) and cell-mediated immunity (mediated by T lymphocytes).

9. Classes of lymphocytes. B lymphocytes recognize soluble antigens and develop into antibody-secreting cells. Helper T lymphocytes recognize antigens on the surfaces of antigen-presenting cells and secrete cytokines, which stimulate different mechanisms of immunity and inflammation. Cytolytic T lymphocytes recognize antigens on infected cells and kill these cells. Natural killer cells use receptors that are not fully identified to recognize and kill their targets, such as infected cells.

10. organi linfoidi • cellule circolanti

11. IL SISTEMA IMMUNITARIO: • organi e cellule • sistema circolatorio ematico • sistema circolatorio linfatico

13. Overview of immune responses in vivo. Antigens are captured from their site of entry by dendritic cells and concentrated in lymph nodes, where they activate naive lymphocytes that migrate to the nodes through blood vessels. Effector and memory T cells develop in the nodes and enter the circulation, from which they may migrate to peripheral tissues. Antibodies are produced in lymphoid organs and enter the circulation, from which they may locate antigens at any site. Memory cells also enter the circulation and may reside in lymphoid organs and other tissues. This illustration depicts the key events in an immune response to a protein antigen in a lymph node; responses in other peripheral lymphoid organs are similar.

15. LE CELLULE DEL SISTEMA IMMUNITARIO

17. CD34 Sca1 Hematopoiesis. The development of the different lineages of blood cells is depicted in this "hematopoietic tree." The roles of cytokines in hematopoiesis are illustrated in Chapter 11, Figure 11-15. CFU, colony-forming unit.

19. Phases of lymphocyte activation. Naive B lymphocytes (top panel) and T lymphocytes (bottom panel) respond to antigens and second signals by protein synthesis, cellular proliferation, and differentiation into effector and memory cells. Homeostasis is restored as many of the antigen-activated lymphocytes die by apoptosis. Note that these phases of lymphocyte responses correspond to the phases of adaptive immunity.

21. I LINFOCITI (IMMUNITA' ACQUISITA O SPECIFICA) Linfocita T citotossico CD8+ Linfocita B Linfocita T helper CD4+ I linfociti naive o vergini, cioè che non hanno mai incontrato l’antigene, circolano attraverso il sistema circolatorio linfatico ed ematico tra tutti gli organi linfoidi secondari.

22. Figure 2-2 Morphology of lymphocytes. A. Light micrograph of a lymphocyte in a peripheral blood smear. B. Electron micrograph of a small lymphocyte. (Courtesy of Dr. Noel Weidner, Department of Pathology, University of California, San Diego.) C. Electron micrograph of a large lymphocyte (lymphoblast). (From Fawcett DW. Bloom & Fawcett Textbook of Histology, 12th ed. WB Saunders, Philadelphia, 1994.)

23. Morphology of plasma cells. A. Light micrograph of a plasma cell in tissue. B. Electron micrograph of a plasma cell. (Courtesy of Dr. Noel Weidner, Department of Pathology, University of California, San Diego.)

24. Dimensioni dei linfociti • Naïve: 8-10 um di diametro • Attivati 10-12 um di diametro Espansione dei linfociti Linfociti T 50000 Linfociti B 5000

25. Come distinguiamo le popolazioni linfocitarie? • Le popolazioni linfocitarie si differenziano grazie ai marcatori di superficie (CD), • Le possiamo vedere al FACS grazie ad anticorpi monoclonali specifici per le proteine di superficie

26. Cellule Accessorie Non presentano un recettore specifico ma cooperano all’avvio delle risposte immunitarie specifiche 1) Fagociti mononucleati 2) Cellule dendritiche 3) Cellule follicolari dendritiche

27. Fagociti mononucleati • Sono specializzati per fagocitare I microbi • Si possono trovare in aggregati plurinucleari • Hanno funzioni effettrici in immunita’ innata e sono in stretta collaborazione con l’immunita’ acquisita: - fagocitano microbi opsonizzati, • secernono citochine per attivare i T • presentano l’antigene ai linfociti T

28. Sistema nervoso centrale fegato Maturation of mononuclear phagocytes. Mononuclear phagocytes develop in the bone marrow, circulate in the blood as monocytes, and are resident in all tissues of the body as macrophages. They may differentiate into specialized forms in particular tissues. CNS, central nervous system.

29. Morphology of mononuclear phagocytes. A. Light micrograph of a monocyte in a peripheral blood smear. B. Electron micrograph of a peripheral blood monocyte. (Courtesy of Dr. Noel Weidner, Department of Pathology, University of California, San Diego.) C. Electron micrograph of an activated tissue macrophage showing numerous phagocytic vacuoles and cytoplasmic organelles. (From Fawcett DW. Bloom & Fawcett Textbook of Histology, 12th ed. WB Saunders, Philadelphia, 1994.)

30. Le cellule dendritiche captano gli antigeni in periferia, alle porte d’entrata dell’orga- nismo e li portano agli organi linfoidi secondari, affinchè siano visti dai linfociti

31. CELLULE DENDRITICHE FOLLICOLARI(FDC) Non deriva da precursori midollari Captano Ag legati ad Ab o fattori del complemento Li tengno sulla superficie e fanno si’ che I linfociti B li riconoscano (intervengono nella affinity maturation dei B) Sono presenti solo nel centro germinativo di linfonodi, milza e tessuto linfoide associato alle mucose

32. FUNZIONI DELLE PRINCIPALI CELLULE DEL SISTEMA IMMUNITARIO

33. GLI ORGANI DEL SISTEMA IMMUNITARIO

34. Organi linfoidi primari O generativii Organi linfoidi secondari o periferici Maturation of lymphocytes. Mature lymphocytes develop from bone marrow stem cells in the generative lymphoid organs, and immune responses to foreign antigens occur in the peripheral lymphoid tissues.

35. ORGANI LINFOIDI anello di Waldeyer (tonsille, adenoidi) timo midollo osseo tessuto linfoide associato ai bronchi linfonodi milza placche di Peyer

36. IL MIDOLLO OSSEO

37. CD34 Sca1 Citochine stromali guidano l’emopoiesi (es: CFS) Hematopoiesis. The development of the different lineages of blood cells is depicted in this "hematopoietic tree." The roles of cytokines in hematopoiesis are illustrated in Chapter 11, Figure 11-15. CFU, colony-forming unit.

38. Emopoiesi del feto: sacco vitellino e mesenchima paraortico, piu’ tardi in fegato e milza • Emopoiesi neonato: midollo osseo ossa spugnose • Emopoiesi in puberta’: sterno vertebre ossa iliache e costole.

39. SCHEMA DEL MIDOLLO OSSEO EMOPOIETICO IN UN OSSO LUNGO Midollo rosso Seni vascolari

40. MIDOLLO OSSEO EMOPOIETICO A PICCOLO INGRANDIMENTO

41. ORGANI LINFOIDI anello di Waldeyer (tonsille, adenoidi) timo midollo osseo tessuto linfoide associato ai bronchi linfonodi milza placche di Peyer

42. IL TIMO

43. TIMO: SUA LOCALIZZAZIONE ANATOMICA

44. SCHEMA DEL TIMO

45. SCHEMA DI SEZIONE DI TIMO Cellule dendritiche linfoidi

46. - Linfocit ma + maturii +linfociti meno maturi Morphology of the thymus. A. Light micrograph of a lobe of the thymus showing the cortex and medulla. The blue-stained cells are developing T cells called thymocytes. (Courtesy of Dr. James Gulizia, Department of Pathology, Brigham and Women's Hospital, Boston.) B. Schematic diagram of the thymus illustrating a portion of a lobe divided into multiple lobules by fibrous trabeculae.

47. SEZIONI DI TIMO

48. IL LINFONODO Aggregati nodulari di tessuto linfoide dove ha origine la risposta immunitaria specifica ad atigeni proteici veicolati per via linfatica

49. 1 3 5 6 4 7 Dell’Ilo 8 9 2

50. Morphology of a lymph node. A. Schematic diagram of a lymph node illustrating the T cell-rich and B cell-rich zones and the routes of entry of lymphocytes and antigen (shown captured by a dendritic cell). B. Light micrograph of a lymph node illustrating the T cell and B cell zones. (Courtesy of Dr. James Gulizia, Department of Pathology, Brigham and Women's Hospital, Boston.)