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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