1. GLAVNI KOMPLEKS GENA TKIVNE PODUDARNOSTI
OBRADA I PREZENTACIJA ANTIGENA

2. GLAVNI KOMPLEKS GENA TKIVNE PODUDARNOSTI
Definicija i osnovne karakteristike
Struktura produkata I i II klase MHC
Struktura i organizacija gena MHC
Nasledjivanje i ekspresija gena MHC

3. GLAVNI KOMPLEKS GENA TKIVNE PODUDARNOSTI
MHC
MAJOR HISTOCOMPATIBILITY COMPLEX

4. MHC=CENTAR IMUNOLOŠKOG UNIVERZUMA
Uloga u:
diferencijaciji T limfocita (pozitivna i negativna selekcija u
timusu)
preživljavanju i homeostatskoj proliferaciji naivnih T limfocita
prepoznavanju antigena i efektorskoj funkciji T limfocita

5. 5 Downloaded from: StudentConsult (on 19 March 2009 11:40 AM)
© 2005 Elsevier 5

6. 6 Downloaded from: StudentConsult (on 19 March 2009 11:40 AM)
© 2005 Elsevier 6

7. H-2
GPLA
DLA
MHC
FLA
RT-1
SLA

8. Humani leukocitni antigeni
HLA
Humani leukocitni antigeni

9. POLIGENSKI
POLIMORFNI

10. George Snell
Jean Dausset
Baruj Benacerraf
1980

15. Figure 3-23

17. A B C MHC II klasa MHC I klasa SVE ĆELIJE SA JEDROM DP DQ DR MAKROFAGI
B LIMFOCITI
DENDRITSKE ĆELIJE A a DP a b
b2m a a DQ b B
b2m a a b DR C
b2m
MHC II klasa
MHC I klasa

18. CD4+ T limfocit CD8+ T limfocit A P C A P C TCR TCR CD4 CD8 MHC II

19. Peter C. Doherty
Rolf M. Zinkernagel
1996

20. Figure 5-12

21. GLAVNI HISTOKOMPATIBILNI KOMPLEKS GENA
6. hromozom
centromera
telomera DP DQ DR
TNF
C4B C4A Bf C2 a b B C E A F G
II KLASA
III KLASA
I KLASA
LMP7
TAP1
LMP2
TAP2

22. Hromozom 6 Regioni: II III I GLAVNI HISTOKOMPATIBILNI KOMPLEKS GENA
HLA-B
HLA-C
HLA-A

23. HLA-B
HLA-C
HLA-A
Jedan
hromozom
Geni
HLA-B
HLA-C
HLA-A
Plazma
membrana

24. Hromozom 6
Regioni II III I
DPB
DPA
DQB
DQA
DRB
DRA

25. Geni DQ beta DP beta DQ alfa DR beta DP alfa DR alfa Plazma membrana
molekul
DR beta
DR alfa DR DP
Plazma
membrana

27. Figure 5-14 part 1 of 2

29. OBRADA I PREZENTACIJA ANTIGENA
Dva puta obrade i prezentacije antigena
(endogeni, egzogeni)
Antigen-prezentujuće ćelije (APĆ)
Aktivacija APĆ

30. OBLICI ANTIGENA KOJE PREPOZNAJU
T LIMFOCITI
Većina T limfocita prepoznaje samo peptidne
antigene.
2. T limfociti prepoznaju samo linearne determinante.
3. T limfociti prepoznaju i odgovaraju na
strane antigene samo kada se oni nalaze na
površini drugih ćelija.

31. DVA PUTA OBRADE I PREZENTACIJE
ANTIGENA
Put MHC I klase
Put MHC II klase

32. ZAJEDNIČKA SVOJSTVA ĆELIJSKIH PUTEVA KOJI UČESTVUJU U OBRADI I PREZENTACIJI ANTIGENA
Peptidni antigeni nastaju proteolizom intaktnih proteina u subcelularnim organelama APĆ.
Vezivanje peptida za molekule MHC odigrava se pre njihove ekspresije na površini ćelije.
Oba puta obrade i prezentacije antigena koriste subcelularne organele i enzime koji imaju opšte funkcije u degradaciji i recirkulaciji proteina.
Oba puta obrade i prezentacije antigena ne razlikuju normalne sopstvene proteine od stranih antigena.

46. The Nobel Prize in Chemistry 2004
"for the discovery of ubiquitin-mediated protein degradation"
The Nobel Prize in Chemistry 2004
                          
Aaron Ciechanover
Avram Hershko
Irwin Rose
    1/3 of the prize
Israel
USA
Technion – Israel Institute of Technology Haifa, Israel
University of California Irvine, CA, USA
b. 1947
b (in Karcag, Hungary)
b. 1926

48. Peptide loading and editing by HLA-DM48

49. I

50. I

51. I

52. I I

53. I

54. I

55. I

56. ANTIGEN-PREZENTUJUĆE ĆELIJE

57. Figure 8-14

64. GLAVNI KOMPLEKS GENA TKIVNE PODUDARNOSTI
Definicija i osnovne karakteristike
Struktura produkata I i II klase MHC
Struktura i organizacija gena MHC
Nasledjivanje i ekspresija gena MHC
OBRADA I PREZENTACIJA ANTIGENA
Dva puta obrade i prezentacije antigena
(endogeni, egzogeni)
Antigen-prezentujuće ćelije (APĆ)

65. Neuropilin-1–neuropilin-1 and ICAM3–DC-SIGN interactions have important roles in the initial contact between naive T cells and antigen-presenting cells (APCs) (antigen-independent). Next, the antigenic peptide–MHC complex becomes available, and the expression of various co-stimulatory molecules (such as CD40 and CD80/CD86) is upregulated on the surface of APCs. These molecules reciprocally stimulate T cells and APCs. SEMA4D (CD100) and SEMA4A, which are expressed by T cells and APCs, respectively, are involved also in antigen-dependent cell–cell contacts. In interactions between helper T cells and B cells, SEMA4D–CD72 interactions enhance the effects of CD40–CD154 (CD40L) interactions. SEMA4D might enhance the sensitivity of APCs to various stimuli by suppressing the inhibitory signals of CD72. At present, it is not clear whether membrane-bound or soluble SEMA4D has the main role in APC activation. SEMA4A seems to have a role in the relatively later phase of T-cell–APC interactions, because the expression of TIM2 is induced on activated T cells. SEMA7A, the expression of which is induced on activated T cells, is involved in the activation of macrophages and monocytes, resulting in the production of pro-inflammatory cytokines. DC, dendritic cell; DC-SIGN, DC-specific ICAM-grabbing non-integrin; ICAM, intercellular adhesion molecule; LFA1, leukocyte function-associated antigen 1; TCR, T-cell receptor; TIM2, T-cell, immunoglobulin domain and mucin domain protein 2.

67. 1. Pathways for cross-presenting antigen
1. Pathways for cross-presenting antigen. Particulate antigen is internalized into phagosomes. Early in this process, phagosomes fuse with the endoplasmic reticulum (ER) and thereby acquire the endoplasmic reticulum−resident antigen-presentation machinery (TAP, tapasin and MHC class I molecules) as well as the Sec61 translocon. Some of the internalized antigen is transferred from the phagosome to the cytosol, possibly by retro-translocation through Sec61 and ubiqitination by ubiquitin (Ub)-conjugating enzymes (UBCs). This antigen is then cleaved by proteasomes that associate with the phagosome membrane, and some of the resulting peptides are transferred back into the phagosome by TAP. In some situations ('vacuolar' pathway), the internalized antigen may also be cleaved into peptides by proteases in the phagosome. Tapasin may help load these peptides onto class I molecules, which are then transported to the cell surface. C.C.
Close window ©2007