1. Dr. Antonio Condino Neto Professor Associado Livre-Docente
Departamento de Imunologia
Instituto de Ciências Biomédicas
Universidade de São Paulo
Imunidade Inata:
Mecanismos Efetores
Dr. Antonio Condino Neto
Professor Associado Livre-Docente

2. Figure 2-1
Imunidade Inata x Imunidade Adaptativa

3. Figure 2-2 part 1 of 2

4. Figure 2-2 part 2 of 2

5. Exemplo de Resposta à Infecção
Figure 2-3

6. Figure 2-4

7. Figure 2-5 part 1 of 2

8. Figure 2-5 part 2 of 2

9. Fagocitose
Figure 2-6

10. NADPH-Oxidase Gene Cromossomo Frequência (%) gp91-phox Xp21.1 675
p47-phox
7q11.23 33
p67-phox
1q25
G6PD
Xq28
<0.01
Adaptado de Curnutte et al, 2002

11. Figure 2-8 part 1 of 2

12. Figure 2-8 part 2 of 2

13. Figure 2-9

14. Figure 2-10

15. Figure 2-11

16. Figure 2-12

17. TLR Ligands - Recognition
PAMPS
TLR
Ligand
Source
TLR1/2
lipoarabinomanin
mycobacteria
TLR2±6
Zymosan
Fungi
TLR3
DS RNA
Viruses
TLR4
lipopolysaccharide
Peptidoglycan
RSV fusion protein
Gr- bacteria
Gr+ bacteria
RSV
TLR5
Flagellin
Flagelated bacteria
TLR6/2
Diacyl lipopeptides
Mycoplasma
TLR7 and 8
SS RNA
Imidazoquinolones
Synthetic
TLR9
CpG
Bacteria and DNA viruses
TLR10
Unknown

18. Figure 2-13

19. TLR signal generation to NF-kB after ligation
CD14
MD2
Cell membrane
TIRAP
TIRAP
TLR 7/8/9
MyD88
TLR 3
MyD88
Endosome
MyD88
IRAK4
TRIF
TRAF6
RIP1
MyD88
NEMO
Slide 3: TLR pathway image
This is a schematic diagram representing the TLR signaling pathway. TLR recognize pathogen associated molecular patterns and can be found on the cell surface or intracellularly. All TLR can function by activation of the IKK complex. Once assembled, IKK directs the phosphorylation and ubiquitination of IkB, targeting it for proteosomal degradation. This in turn allows NF-kB to dimerize and translocate to the nucleus, thus promoting gene transcription.
Clearly there are molecules in this pathway that, when defective, can almost completely abrogate TLR function, one example being the human mutation of IRAK4 and another being that of NEMO. (here is boy w/NEMO mut ahving the characteristic syndrome of ED). There are conceivably also more upstream mutations that selectively impair TLR function. This is something that we are interested in investigating further in the future.
IKK-
IKK- p
IkB
IkB
Cytoplasm
NF-B
Nucleus
New gene transcription
NF-B binding motif

20. TLR induction of other transcription factors
CD14
MD2
Cell membrane
TIRAP
TRAM
TIRAP
TLR 7/8/9
MyD88
TLR 3
TRIF
MyD88
Endosome
MyD88
TRIF
IRAK4
MyD88
TRAF6
IRAK1/4
IRF5
TRAF6
IRF7
Slide 3: TLR pathway image
This is a schematic diagram representing the TLR signaling pathway. TLR recognize pathogen associated molecular patterns and can be found on the cell surface or intracellularly. All TLR can function by activation of the IKK complex. Once assembled, IKK directs the phosphorylation and ubiquitination of IkB, targeting it for proteosomal degradation. This in turn allows NF-kB to dimerize and translocate to the nucleus, thus promoting gene transcription.
Clearly there are molecules in this pathway that, when defective, can almost completely abrogate TLR function, one example being the human mutation of IRAK4 and another being that of NEMO. (here is boy w/NEMO mut ahving the characteristic syndrome of ED). There are conceivably also more upstream mutations that selectively impair TLR function. This is something that we are interested in investigating further in the future.
TBK1
MAPK
AP-1
IRF3
Cytoplasm
Nucleus
New gene transcription

21. Figure 2-15

22. Figure 2-39

23. Figure 2-41 part 1 of 2

24. Figure 2-41 part 2 of 2

25. Figure 2-45

26. Figure 2-46

27. Figure 2-47

28. Figure 2-44

29. Figure 2-42

30. Figure 2-43

31. Quimiotaxia de Neutrófilos
(CD11a/CD18)
LAD- II
LAD- I
E-Selectin
Sialyl-Lewis-X
Rolagem
Adesão
Emigração Transendotelial

32. Lesão Cutânea em Paciente com LAD-I
Leucócitos cels/mm3

33. Figure 2-48

34. Figure 2-49

35. Figure 2-50

36. Figure 2-52

37. Figure 2-53

38. Figure 2-20

39. Figure 2-18

40. Figure 2-19

41. Figure 2-21

42. Figure 2-24

43. Figure 2-23

44. Figure 2-27

45. Figure 2-29

46. Figure 2-34

47. Figure 2-36

48. Figure 2-31

49. Figure 2-35