1. APC & Antigen presentation

2. antigen-presenting cell, APC
Concept
A group of immune cells, whose role is to take up, process and present antigenic peptides to T cells.

3. Professional APC Non-professional APC
Macrophages, dendritic cells, and B cells, which can express MHC class II molecules.
Non-professional APC
Other cell type capable of expressing MHC class II molecules
eg. Endothelial cells, EC
Fibroblasts
Activated T cell

7. 1 Dendritic cell，DC highly branched morphology
can active naive T cells
markers

8. 1) Markers secreting cytokines CD1a, CD11c, CD83
Pathogen receptor, FcR
MHC II
co-stimulating factors (CD80,CD86)
Adhesion molecular CD40
CD54 (ICAM-1), etc.
secreting cytokines
IL1, IL-6, IL-12, TNF-a, IFN-a, chemokines

9. 2) Source, distribution and classification Source
DC are bone marrow-derived
Myeloid DC
Lymphoid DC

11. Bone marrow Blood Tissue
dendritic cell
Monocyte
Indeterminate
cell
Dendritic cell
Macrphage
Mycloid precursor
Pluripotent stem cell ?

12. Distribution and classification
DCs are found in many organs throughout the body
DC in lymphoid tissue
Interdigitating cell, IDC
Follicular DC, FDC
thymic dendritic cell, TDC
DC not in lymphoid tissue
Langerhans cells
Interstitial DC
DC in body fluid
Veiled cells
Peripheral blood DC

13. interdigitating DC, IDC
IDC express high levels of MHC molecules, and are more potent antigen-presenting cells than others.

14. follicular DC, FDC FDC B cells
FDC express high levels of membrane receptors for antibody and complement. By these, FDC actives the B cells in lymph nodes.

15. Langerhan’s cells, LC
Langerhans cells found in the epidermis (skin) and mucous membranes (left), expressing high levels of FcR, receptor of complement, and MHC. Birbeck granule is the characteristic organelle. After capturing antigen in the tissues by phagocytosis or by endocytosis. DC migrate into the blood or lymph and circulate to lymphoid organs, become IDC（right）。

16. Cell MHC-II FcR C3bR Birbeck
FDC ++/
IDC (I,II)
TDC ? +
LC (I,II) + + +
Interstitial DC ? ? +
VC ? ? --
M ++/ BL

17. 3) Differentiation, development, maturing and migration
Lymphoid DC
DC in lymph, negative selection of T cells
myeloid DC
Immature
mature

18. Four phases Pre-DC Immature DC Migration Mature DC Monocyte, Mo
Uptake antigen
Express MHC
Secrete chemokines
Migration
Mature DC
Express high levels of MHC I and II, CD80, CD86, CD40, CD54, HSP, etc.

19. 4) activation and tolerance Activation
First signal (MHC-peptide)
Second signal (co-stimulating factors)
Adhesion molecular
Cytokines (IL-12)
Tolerance
Negative selection

20. 2 Mononuclear phagocyte system, MPS
Macrophages (Mf) are phagocytic cells of monocytic lineage residing within tissues and are particularly well equipped for effective antigen presentation.

21. Different names in different tissues
Monocyte ( blood )
Kupffer cells ( liver )
Mesangial cells ( kidney glomerulus )
Microglia ( brain )
Alveolar macrophages ( lung )
Histiocyte ( connective tissue )

22. The process of M activation
rested M
responsive M
stimulated M
activated M
suppressor M
病原体
signal
LFA-1
MHC-II
细胞增生
趋化，杀菌
提呈Ag，
激活LC，
结合TC，
过度活化
适度活化
PGE
抑制免疫功能
杀瘤，杀菌
First signal:
MAF/IFN-,
MSF
second signal:
LPS/IFN-,
MSF,CK, 1 2 3

23. markers Functions MHC II CR1（CD35） CR3（CD11b/CD18） IgG Fc受体 Receptors
Enzymes
Cytokines

24. 扫描电镜显示，在感染早期，M伸出长长的伪足去捕获细菌

26. Biologic effects of M

28. 3 B cell bone marrow-dependent lymphocyte
About 5-15% of the circulating lymphoid pool are B cells difined by the presence of surface immunoglobulin.

29. Markers of B cells

30. Characteristics of B cells
not actively phagocytic
Class II-positive
BCR

31. Antigen-presenting cells
APC
Present to
Macrophage
T cell via MHC antigen
Dendritic cells
B cells
T cell via antigen captrue by surface antibody and MHC antigen
Activated T cells

32. ANTIGEN PROCESSING AND PRESENTATION

33. Binding and uptake of antigen
depends on the physical state of the antigen and the cell type involved.
Antigen processing
MHC class I processing pathway
MHC class II processing pathway
Antigen presentation

34. 1 Binding and uptake of antigen
exogenous antigens
Bacteria, cells and soluble proteins
processed by APC
endogenous antigens
Produced within the cells, Such as viral proteins or tumor proteins
processed by host cell

36. Uptake antigen by immature DC
Pinocytosis
Liquid or small granule
Receptor-mediated endocytosis
effective
selective
saturated
FCR, 甘露糖R
Phagocytosis
Large molecular or microbe

37. Uptake antigen by MPC Phagocytosis Pinocytosis Endocytosis
Large solid or molecular complex, such as bacteria, fragment of cells, etc.
Phagecyte (mf, granulocyte)
Pinocytosis
Receptor-mediated pinocytosis
Endocytosis
Low levels of particulate or soluble antigens
exocytosis

38. Uptake antigen by B cells
nonspecifically engulfed
BCR-mediated

39. 2 Antigen processing
Degradation of externally- or internally- derived antigen into short peptide sequences
Association of the peptide with MHC molecules

40. Two antigen-processing pathways
MHC class I
MHC class II
Major antigen sources
endogenous antigen
exogenous antigen
Processing machinery
proteasome
lysosomal enzymes
Cell type where active
all nucleated cells
professional APCs
Site of antigen-MHC binding
endoplasmic reticulum
lysosome and endosome
MHC utilized
Presents to
CD8+ T cell (Tc)
CD4+ T cells (Th)

41. MHC class I processing pathway

43. MHC class I processing pathway
Antigenic protein proteosome peptide fragment released into cytosol binds to TAP protein moves to endoplasmic reticulum(ER)
Newly synthesized Class I a chain and b2 microglobulin move to ER calnexin binds to a chain peptide fragment and b2m bind to a chain release of a chain from calnexin complex moves to Golgi apparatus glycosylation in Golgi apparatus secretory vesicle plasma membrane

44. Structure of MHC class I

45. proteasome
LMP, low molecular weight polypeptide or large multifunctional protease
Structure:
20S 26S
Function:
Degradation of protein

46. 26S protease cmplex 20S proteasome twin 19S cops

47. TAP, transporter associated with antigen processing
structure:
TAP-1 and TAP-2
function:
transports small peptides (8-13 aa) to the ER

49. calnexin Structure Function
88kD integral ER membrane chaperone protein
Function
Binds to a nascent MHC class I a chain after release from a ribosome into the ER lumen so that the a chain will not leave the ER until it binds both a short peptide sequence and b2 microgobulin

50. Molecular chaperones: calnexin, calreticulin,tapasin

51. MHC class II processing pathway

53. MHC class II processing pathway
Antigenic protein endosome/lysosome peptide fragment
Newly synthesized class II molecules move to ER and associate with invariant chain protein molecule move to Golgi apparatus move to endosomes/lysosomes release of invariant chain from class II molecule class II binds antigenic peptide fragment transport to cell surface

54. Structure of MHC class II

55. Endosome & lysosome acidic protease & lysosome enzymes Function
Degrade protein into peptide fragments (10-30 aa)

56. invariant chain, Ii Function Promote the formation of MHC II a b dimer
Directs the movement of newly synthesized class II molecules into the Golgi and then the late endocytic compartment of the cell
Prevent the binding of antigenic peptides to class II molecules, at least until the class II molecule reaches the late endocytic compartment

57. CLIP, class II associated invariant chain peptides

58. 3 Antigen presentation Antigen presentation
The activation of T cells via T cell receptors, which specifically recognize antigenic peptide in association with either MHC class I or II molecules on the surface of APC.