1 BNG 331 Cell-Tissue Material Interactions Wound Healing I
2 Course update LBL 4 Friday; paper posted Need 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 angiogenesis and healing around implants)
3 Recap acquired immunity
4 Complement System Cascade of activated enzymes Virtually all biomaterials activate cascade through the alternative pathway! Part of the innate immune response Key complement component is C3b, which directly binds the microbe By-products of coagulation, kallikrein and plasmin, activate the classic and alternative pathways
5 Clonal selection theory (1) Hematopoietic stem cell undergoes differentiation into (2) Immature lymphocytes with many antigen receptors Each lymphocyte produces a single type of 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 that do (5) (6) produce many clones of themselves Where did these antigen receptors come from?
6 Back to the central dogma of molecular biology The DNA that we get from our parents! We already have the machinery needed to combat most pathogens! T-cell (antigen) receptors are just proteins, which are coded for by
7 An aside: maternal IgG transfer In addition to the genetic information needed to produce antigen receptors and specificity, we also get a fair amount of Ab directly from the mother In humans, only IgG type transferred to fetus Starter supply of IgG provides protection to the infant while his/her humoral response is still inefficient
8 Connecting to last lecture In all the steps shown here, some (very small) percentage of lymphocytes already possessed specificity to the antigen shown! Ok, so what about exposure to a new pathogen?
9 Thought questions for Chapter 6 Are the following true or false? If false, why? Cytotoxic T-lymphocytes receive information about the 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 for detection by t-cells
10 Let s tie together Chapters 4-6 Chemotaxis & Activation of Leukocytes Complement system Foreign Surface Kallikrein Factor XII Fibrinolysis Intrinsic Pathway Coagulation Fibrin Production
11 Wound Healing Injury coagulation inflammation wound healing Natural response to injury Body is able to: - regenerate cells characteristic and specific to certain tissues and organs - replace connective tissue and blood vessels angiogenesis
12 Wound Healing proliferative phase Introduce some of the components today and discuss the process next class
13 Tissues Consist of pertinent and specific cells, distinct from blood cells, and extracellular matrix (ECM) that is formed and maintained by chemical compounds (proteins) synthesized by cells Where there is tissue injury, the morphology, function, and phenotype of the cells are affected
14 Tissues Examples of cell responses to injury Atrophy decrease in size/number (from apoptosis) Hypertrophy increase in size Change in phenotype
15 Tissues Another aspect that critically affects the outcome of wound healing is the regenerative capacity of cells Labile cells multiply continously throughout life e.g., digestive and respiratory tract, skin cells, bonemarrow 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 muscle cells Permanent or static cells do not multiply Examples? Hint: we have discussed a couple of these!
16 Vascularized connective tissue: pertinent aspects of hemostasis and inflammation Damaged BV formation of blood clot Plugs the defect provides temporary protection to the exposed wound site Provisional matrix for cells to attach and migrate during healing Initiation of inflammation
17 Vascularized connective tissue: pertinent aspects of hemostasis and inflammation Growth factors peptides and proteins that stimulate cell 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 or paracrine matter (what s the difference?)
18 Vascularized connective tissue: pertinent aspects of hemostasis and inflammation Activated leukocytes release growth factors during inflammation! Neutrophils release proinflammatory cytokines that activate local connective tissue cells Macrophages release fibroblast GF (FGF), platelet derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) FGF-10 (~20 kda) PDGF (~16 kda) VEGF (~42 kda)
19 Exam 1 Average: 75.5 Standard deviation: 10.3 Median: Adjusted grading scale: A 88+ A B B B C C C D 56- Frequency Score
20 Exam 1 points Problem 2 proteins and surface interactions Vroman effect: bonds must periodically break to allow dislocation of lower affinity proteins Problem 4 clarification on statement 3 in T/F (indigestible particles) No need to include information that isn t asked for! Problem 3: describe differences in the coagulation response between scenarios any commentary on intrinsic pathway needed? Exam solution posted later today