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Wound Healing I
BNG 331 Cell-Tissue Material Interactions
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Course update
LBL 4 Friday; paper postedNeed a volunteer to switch groups!
Much better job on LBL 3 figure summaries
BNG spring seminar 3 this Thursday
Lippman 017, common hour Schedule for today:
End of Chapter 6 Generating Specificity
Introduction to Chapter 7 Wound healing
Return Exam 1 (and other assignments)
Next time:A closer look at the wound healing response (focusing
on angiogenesisand healing around implants)
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Recap acquired immunity
http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__the_immune_response.html -
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Complement System
Cascade of activatedenzymes
Virtually all biomaterialsactivate cascade throughthe alternativepathway! Part of the innate immune
response
Key complementcomponent is C3b, whichdirectly binds the microbe
By-products ofcoagulation, kallikrein andplasmin, activate theclassic and alternative
pathways
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Clonal selection theory
(1) Hematopoietic stem cell undergoes
differentiation into
(2) Immature lymphocytes with manyantigen receptors
Each lymphocyte produces a single typeof receptor with a unique specificity to
one ligand (antigen)(3) self-recognizing lymphocytes are
destroyed, while the rest
(4) mature into inactive lymphocytes(most of these will never encounter
a matching antigen!). Those thatdo (5)
(6) produce many clones of
themselves
Where did these antigen receptors come from?
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Back to the central dogma of
molecular biology
T-cell (antigen) receptorsare just proteins, whichare coded for by
The DNA that we get fromour parents!
We already have the machineryneededto combat most pathogens!
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An aside: maternal IgG transfer
In addition to the genetic information needed toproduce antigen receptors and specificity, we also geta fair amount ofAbdirectly from the mother
http://openi.nlm.nih.gov/imgs/rescaled512/
In humans, only IgG typetransferred to fetus
Starter supply of IgG
provides protection tothe infant while his/herhumoral response is stillinefficient
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Thought questions for Chapter 6
Are the following true or false? If false, why?
Cytotoxic T-lymphocytes receive information aboutthe antigen from macrophages and transmit them to
natural killer cells and B-lymphocytes For a given antigen, the matching T-cell receptor and
the Fab of a matching Ab are similar in structure
An antigen-presenting cell (APC) refers to an infected
cell, which displays the antigen on its surface fordetection by t-cells
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Lets tie together Chapters 4-6
Foreign Surface
Factor XII
Intrinsic Pathway Coagulation
Fibrin Production
FibrinolysisKallikrein
Complement system
Chemotaxis & Activation of Leukocytes
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Wound Healing
Injury coagulation inflammation woundhealing
Natural response to injury
Body is able to:
- regenerate cellscharacteristic and specificto certain tissues and
organs- replace connective tissueand blood vessels
angiogenesis
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Wound Healing
proliferativephase
http://en.wikipedia.org/wiki/File:Wound_healing_phases.png
Introduce some of the components today and discuss theprocess next class
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Tissues
Consist of pertinent andspecific cells, distinctfrom blood cells, andextracellular matrix
(ECM) that is formed andmaintained by chemicalcompounds (proteins)synthesized by cells
Where there is tissueinjury, the morphology,function, and phenotypeof the cells are affected
https://reader010.{domain}/reader010/html5
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Tissues
Examples of cell responses to injuryAtrophy decrease in size/number (from apoptosis)
Hypertrophy increase in size
Change in phenotype
http://www.vet.uga.edu/ http://origin-ars.els-cdn.com/content/
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Tissues
Another aspect that critically affects the outcomeof wound healing is the regenerative capacity ofcells
Labile cells multiply continously throughout life
e.g., digestive and respiratory tract, skin cells, bone-marrow derived stem cells
Two strategies for replacement of these cells?
Stable cells multiply upon injury
e.g., parenchyma of most solid tissues (liver, kidney,pancreas), fibroblasts, endothelial cells, smooth musclecells
Permanent or static cells do not multiply
Examples? Hint: we have discussed a couple of these!
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Vascularized connective tissue: pertinent
aspects of hemostasis and inflammation
Damaged BV formation ofblood clot
Plugs the defect provides
temporary protection to theexposed wound site
Provisional matrix for cells toattach and migrate during
healingInitiation of inflammation
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Vascularized connective tissue: pertinent
aspects of hemostasis and inflammation
Growth factors peptidesand proteins that stimulatecell differentiation,proliferation, migration, and
other functions May induce cell migration via
chemotaxis
May increase rate of random,
undirected cell migration GFs produced by a cell can
act in an autocrine orparacrine matter (whats the
difference?)http://www.crmagazine.org/SiteCollectionImages/growth%20factor.jpg
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Vascularized connective tissue: pertinent
aspects of hemostasis and inflammation
Activated leukocytes release growth factors duringinflammation!
Neutrophils release proinflammatory cytokines thatactivate local connective tissue cells
Macrophages release fibroblast GF (FGF),plateletderived growth factor (PDGF), andvascular endothelialgrowth factor (VEGF)
FGF-10 (~20 kDa)PDGF (~16 kDa) VEGF (~42 kDa)
http://www.nature.com/nm/journal/v16/n10/images/nm1010-1107-F1.jpg
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Exam 1
Average: 75.5
Standard deviation: 10.3
Median: 77.3
Adjusted grading scale:A 88+A- 83 87
B+ 79 82
B 73 78
B- 70 72
C+ 66 69
C 62 65
C- 57 61
D 56-
45 50 55 60 65 70 75 80 85 90 950
1
2
3
4
5
6
Score
Frequency
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Exam 1 points
Problem 2 proteins and surface interactions
Vroman effect: bonds must periodically break toallow dislocation of lower affinity proteins
Problem 4 clarification on statement 3 in
T/F (indigestible particles) No need to include information that isnt
asked for!
Problem 3: describe differences in the coagulationresponse between scenarios any commentary onintrinsic pathway needed?
Exam solution posted later today