Bio 328 Immunology

1
Bio 328 Immunology Leukocyte migration and
inflammation
2
Innate or natural immunity.

• Innate vs adaptive response
• Passive Defenses
• Mechanical properties boundaries
• Chemical properties boundaries
• Inflammatory response
• Mobilization of active defenses
• Initiation of innate responses
• Effectors of the active, innate response
• Soluble mediators
• Cellular mediators

3

• Acute Inflammatory Response
• Mobilization of active defenses
• Vasodilation
• Vascular permeability
• Recruitment of neutrophils
• Localized vs systemic.

4
(No Transcript)
5
(No Transcript)
6
(No Transcript)
7
Tissue damage exposes the blood protein Factor
VII to Tissue Factor expressed on the basolateral
surface of endothelial cells.
8
Kinin system
9
C3bB
C3bBb
10
Plasmin
Bradykinin
11
PlasminogenActivatorinactive
Kallikrein Thrombin Elastase Cathepsin Plasmin
PlasminogenActivatoractive
C3 and C5
Plasminogen
Plasmin
C3a and C3bC5a and C5b
12
(No Transcript)
13
C3 activation
MBL (mannose, fucose) Ficolins (N-aceylglucosamine
) C1q (LPS) CRP-phosphocholine)
Plasmin
kallikrein
Different ways to activate complement.
14
Vasodilation and increased vascular permeability
lead to fluid leakage (edema) and extravasation
of neutrophils.
15
(No Transcript)
16
(No Transcript)
17

• Cellular component of inflammatory response
• Neutrophils phagocytosis.
• (resident) Macrophages and Dendritic cells
  augmentation of acute inflammatory response (and
  initiation of adaptive response).
• Mast cells augmentation of inflammatory response.

18
Lipoxygenase
Cyclooxygenase
Leukotrienes
Prostaglandins
19
(No Transcript)
20
Inflammatory Response
Systemic Response Liver Hypothalamus Bone Marrow
Local Response Epithelial cells Endothelial
cells Macrophages/ Dendritic cells
21
Endothelial cells Cytoskeleton E- and
P-Selectin ICAM-1/2 Interleukin-8 MHC-I
Macrophages/Dendritic cells IL-1, TNFa, IL-6 AA
metabolites iNos, Cox2 Interleukin-8 Defensins MHC
-I, MHC-II
Vasodilation Vasopermeability Recruitment
neutrophils
22
(No Transcript)
23
(No Transcript)
24
(No Transcript)
25
(No Transcript)
26
(No Transcript)
27
(No Transcript)
28
(No Transcript)
29
(No Transcript)
30
C-reactive Protein A Pentraxin
31
(Phosphocholine)
32
Ligand-bound CRP recruits and binds C1q and
activates the classic pathway of
complement, Ligand-bound CRP is recognized by the
Fcg receptor and, thus, is an opsonin.
33

• Resolve the Inflammatory response
• LPS tolerance short form of MyD88, protein
  phosphatases, sTNFaR and sIL-1R, IL-1Ra.
• IL-10 and TGFb.
• Decay-Activating Factor.
• Arachidonic acid metabolites (Charles Serhan).

34
(No Transcript)
35
(No Transcript)
36
Chronic inflammation persistent infections,
autoimmunity, tissue damage, obesity. Macrophages
and TH1 INFg and TNFa (cachectin) Fibrosis and
granuloma
37
(No Transcript)
38
(No Transcript)
39
Chronic Inflammation accumulation and continuous
activation of macrophages.
Fibrosis Scar tissuefibroblast
proliferationcollagen production
Granuloma
40
(No Transcript)
41
William Coley (1862-1936).
42
Coleys toxin
43
(No Transcript)
44
(No Transcript)
45
(No Transcript)
46

• Anti-inflammatory therapy
• Anti-adhesin therapy
• Corticosteroids (prednisone, prednisolone, and
  methylprednisolone
• NSAIDS (aspirine, Tylenol, ibuprofen, Naproxen)

47
Celebrex, Vioxx
48
(No Transcript)
49
(No Transcript)
50
(No Transcript)
51
(No Transcript)
52
(No Transcript)
53
(No Transcript)
54
CR3
55
(No Transcript)
56
(No Transcript)
57
(No Transcript)
58
(No Transcript)
59
(No Transcript)
60
(No Transcript)
61
(No Transcript)
62
(No Transcript)
63

• Extra-vasation cells squeeze between neighboring
  endothelial cells without interupting the
  integrity of the endothelium
• Homotypic binding of PECAM-1 of the leukocyte
  with PECAM-1 of the tight junction of the
  endothelial cells.
• LFA-1 binds to JAM-1 of the junctional complex
• PECAM Platelet Endothelial Cell Adhesion
  Molecule.
• JAM Junctional cell Adhesion Molecule.

64
(No Transcript)
65
PSGL-1 P-selectin Glycoprotein Ligand-1
66
(No Transcript)
67
(No Transcript)
68
(No Transcript)
69
(No Transcript)
70
(No Transcript)
71
(No Transcript)
72
aLb2 LFA-1) a4b1 (VLA-1)
CCL21 CCl19 T cells CXCL12
CXCL13 B cells
73
Gut CCL25binds CCR9
CCL17CCL27CCL1
a4b7
74
The End