Transplant and Wound healing

Question 1

What is regeneration?

Answer 1

growth of cells and tissues to replace lost structures
usual response of skin, liver or intestinal
no scar

Question 2

What is healing with scar?

Answer 2

occurs when complete restitution is not possible; usually collagen deposition(fibrosis); response to severe and chronic damage

Question 3

What are teh requirements for regeneration of parenchyma?

Answer 3

supporting stroma

exisiting cells must be able to proliferate

Question 4

What are labile tissues?

Answer 4

continuous renewal; hematopoietic cells in marrow, surface epithelia, mucosal epithelia

Question 5

What are stable tissues?

Answer 5

parenchyma of most solid organs

regeneration occurs but limited; except for liver

Question 6

What are teh non-dividing cells? How are they repaired?

Answer 6

neurons, cardiac myofibers and skeletal myofibers

repair by connective tissue

Question 7

What are stem cells?

Answer 7

able to self renew and assymetricaly replicate

Question 8

What are the two types of stem cells?

Answer 8

adult adn embryonic; adult have lineage-specific stem cells

Question 9

What does VEGF do?

Answer 9

secreted from mesenchymal cells and induces angiogenesis

Question 10

What is fibroblast growth factor do?

Answer 10

secreted from variety of immune cells; induces angiogenesis; promotes migration of fibroblasts, epithelial cells and macrophages

Question 11

What is PDGF?

Answer 11

platelet derived growth factor, platelets, macrophages, endothelial cells, smooth muscle cell
induce fibroblast smooth muscle, endothelial cell proliferation and migration

Question 12

What is TGFBeta?

Answer 12

transforming growth factor beta, from platelets, endothelium, epithelium, lymphocytes –_ supppreses endothelial proliferation/migration; stim production of ECM proteins

Question 13

What is teh role of the ECM?

Answer 13

mechanical support, regulate cell prolif, provides scaffold essential for healing without scar, storage of growth factors: fibroblasts growth factor, hepatocyte growth factor, creates a microenvironment

Question 14

What type of ecm in the basement membrane?

Answer 14

type 4 collagen
laminin
proteoglycan

Question 15

What are the type of structures found in the intersitial matrix?

Answer 15

fibrillar collagens
elastin
proteoglycan and hyaluronan

Question 16

What is Ehlers-Danlos syndrome?

Answer 16

genetic defect in collagen synthesis or structure
most common is type 5
skin hyperextensable, joints hypermobile, rupture of internal organ and large arteries

Question 17

What is Marfans syndrome?

Answer 17

mutation affecting fibrillin
major component of microfibrils in ECM
degeneration of aorta
dislcoated lens
abnormal valves
long legs and fingers

Question 18

Repair by connective tissue(scar formation) takes place four sequential steps?

Answer 18

angiogenesis
fibroblast migration and proliferation
extracellular matrix deposition
maturation of fibrous tissue

Question 19

What is the role of granulation tissue in healing?

Answer 19

specialized tissue seen in healing
present by 3-5 days contains new vessels
inflammatory cells
fibroblasts
"hallmark" of repair process

Question 20

What are involved in angiogenesis from pre-existing vessels?

Answer 20

ntric oxide, VEGF

Question 21

What is involved in angiogenesis from endothelial precursor cells in bone marrow?

Answer 21

VEGF and FGF

Question 22

What causes fibroblast migratio and proliferationa dn deposition of ECM?

Answer 22

TGFBeta
PDGF
FGF

Question 23

Maturation of fibrous tissue over time casues remodeling of scar, what proteein degrades collagen?

Answer 23

matrix metallopretinases

Question 24

What matrix metalloproteinases contains what metal, and is secreted by what?

Answer 24

zinc

fibroblasts, macrophages, neutrophils

Question 25

What are the three phases of cutaneous wound healing?

Answer 25

inflammation
granulation tissue formation and re-epithialization
wound contraction, ECM deposition and remodeling

Question 26

What is the wound strength at teh end of the 1st week?

Answer 26

10% of unwounded skin

Question 27

What does wound strength plateau at and at what time?

Answer 27

3rd month at 70-80%

Question 28

What factors influence healing?

Answer 28

nutrition: vitamine C deficiency inhibit collagen synthesis
metabolic status
circulatory status
horomones (steroids inhibit TGFBeta and decreases fibrosis)
Infection
Mechanical factors
foreign bodies prologn inflammation

Question 29

What is a coloid?

Answer 29

raised scar due to excess collagen above and beyond injry; TGFbeta and IL1 increased

Question 30

What are formation of contractures?

Answer 30

excessive contraction resulting in deformity

Question 31

What is the HLA complex?

Answer 31

human leukocyte antigen complex

encodes MHC

Question 32

How important is MHC tissue matching for solid organ transplants?

Answer 32

matching of donors and recipient MHC proteins is unimportant now that we utilize cyclopsoring and other immunosuppressive. Still important for kidney transplant

Question 33

What is a minor antigen recognition?

Answer 33

T cell recognizes processed peptide of allogenic MHC molecule bound to self MHC molecule on host APC
due to SNPs

Question 34

What is a hyperacute regection of an organ transplant?

Answer 34

major barrier to xenotransplantation, immediate rejection from complement epithelium, endothelial activation and inflammation

Question 35

What is acute rejection?

Answer 35

cellular or humoral in nature

occurs wihtin days to weeks

Question 36

What is chronic rejection?

Answer 36

major cause of graft failure, vacular changs, interstitial fibrosis, loss of renal parenchyma; get renal ischemia due to loss of glomerulii

Question 37

What is a mixed lymphocyte reaction?

Answer 37

mixing blood of mononulear cells from two donors in tissue culture; can tell reaction

Question 38

What innate immunity provides a barrier to HIV?

Answer 38

physical barrier
PMNs
mononuclear phagocytes
eosinophilic granulocytes
TRIM5alpha, APOBEC3G
Complement cascade