Transplant and Wound healing Flashcards
What is regeneration?
growth of cells and tissues to replace lost structures
usual response of skin, liver or intestinal
no scar
What is healing with scar?
occurs when complete restitution is not possible; usually collagen deposition(fibrosis); response to severe and chronic damage
What are teh requirements for regeneration of parenchyma?
supporting stroma
exisiting cells must be able to proliferate
What are labile tissues?
continuous renewal; hematopoietic cells in marrow, surface epithelia, mucosal epithelia
What are stable tissues?
parenchyma of most solid organs
regeneration occurs but limited; except for liver
What are teh non-dividing cells? How are they repaired?
neurons, cardiac myofibers and skeletal myofibers
repair by connective tissue
What are stem cells?
able to self renew and assymetricaly replicate
What are the two types of stem cells?
adult adn embryonic; adult have lineage-specific stem cells
What does VEGF do?
secreted from mesenchymal cells and induces angiogenesis
What is fibroblast growth factor do?
secreted from variety of immune cells; induces angiogenesis; promotes migration of fibroblasts, epithelial cells and macrophages
What is PDGF?
platelet derived growth factor, platelets, macrophages, endothelial cells, smooth muscle cell
induce fibroblast smooth muscle, endothelial cell proliferation and migration
What is TGFBeta?
transforming growth factor beta, from platelets, endothelium, epithelium, lymphocytes –_ supppreses endothelial proliferation/migration; stim production of ECM proteins
What is teh role of the ECM?
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
What type of ecm in the basement membrane?
type 4 collagen
laminin
proteoglycan
What are the type of structures found in the intersitial matrix?
fibrillar collagens
elastin
proteoglycan and hyaluronan
What is Ehlers-Danlos syndrome?
genetic defect in collagen synthesis or structure
most common is type 5
skin hyperextensable, joints hypermobile, rupture of internal organ and large arteries
What is Marfans syndrome?
mutation affecting fibrillin major component of microfibrils in ECM degeneration of aorta dislcoated lens abnormal valves long legs and fingers
Repair by connective tissue(scar formation) takes place four sequential steps?
angiogenesis
fibroblast migration and proliferation
extracellular matrix deposition
maturation of fibrous tissue
What is the role of granulation tissue in healing?
specialized tissue seen in healing present by 3-5 days contains new vessels inflammatory cells fibroblasts "hallmark" of repair process
What are involved in angiogenesis from pre-existing vessels?
ntric oxide, VEGF
What is involved in angiogenesis from endothelial precursor cells in bone marrow?
VEGF and FGF
What causes fibroblast migratio and proliferationa dn deposition of ECM?
TGFBeta
PDGF
FGF
Maturation of fibrous tissue over time casues remodeling of scar, what proteein degrades collagen?
matrix metallopretinases
What matrix metalloproteinases contains what metal, and is secreted by what?
zinc
fibroblasts, macrophages, neutrophils
What are the three phases of cutaneous wound healing?
inflammation
granulation tissue formation and re-epithialization
wound contraction, ECM deposition and remodeling
What is the wound strength at teh end of the 1st week?
10% of unwounded skin
What does wound strength plateau at and at what time?
3rd month at 70-80%
What factors influence healing?
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
What is a coloid?
raised scar due to excess collagen above and beyond injry; TGFbeta and IL1 increased
What are formation of contractures?
excessive contraction resulting in deformity
What is the HLA complex?
human leukocyte antigen complex
encodes MHC
How important is MHC tissue matching for solid organ transplants?
matching of donors and recipient MHC proteins is unimportant now that we utilize cyclopsoring and other immunosuppressive. Still important for kidney transplant
What is a minor antigen recognition?
T cell recognizes processed peptide of allogenic MHC molecule bound to self MHC molecule on host APC
due to SNPs
What is a hyperacute regection of an organ transplant?
major barrier to xenotransplantation, immediate rejection from complement epithelium, endothelial activation and inflammation
What is acute rejection?
cellular or humoral in nature
occurs wihtin days to weeks
What is chronic rejection?
major cause of graft failure, vacular changs, interstitial fibrosis, loss of renal parenchyma; get renal ischemia due to loss of glomerulii
What is a mixed lymphocyte reaction?
mixing blood of mononulear cells from two donors in tissue culture; can tell reaction
What innate immunity provides a barrier to HIV?
physical barrier PMNs mononuclear phagocytes eosinophilic granulocytes TRIM5alpha, APOBEC3G Complement cascade
