1. Vascular Biology – 4 blood and its components Disclaimer: this is a very broad topic and we won’t be able to get into it in depth.

2. 1. Erythrocytes  ~8 um diameter, 2 um thickness  no nucleus  Hemoglobin in the cytosol: 15g/dL of blood in men, 13.5 g/dL of blood in women. Composition of Hemoglobin changes from fetus to infant.  Iron at the center of hemoglobin – iron is recycled from old erythrocytes very efficiently, but not 100%, eat your spinach (or steak).

4. 2. Leukocytes:  Their job is to clean up debris, aid in detection and destruction of foreign antigens. Main role in the immune response.  Have clearly defined nuclei.  “Granulocytes” have granules in the cytoplasm  Phagocytosis, formation of pseudopodia that engulf the target and bring it into the cytosol, where it gets digested.  Chemotaxis= cell movement in the direction of a concentration gradient. Differences among types of leukocytes has to do with their specificity for antigens and the particular biochemical reactions involved in their function.

5. a. Neutrophils (granulocyte): can digest bacteria through use of hydrogen peroxide, free OH radicals, and oxidation. Can live 4-5 days in extravascular space

6. a. Eosinophils (granulocyte): similar to neutrophils. Involved in asthma, allergies. Can survive for weeks in the extravascular space

7. a. Basophils (granulocyte) immunoglobulin E (igE) receptors on their surface. When stimulated, they trigger a histamine response, local edema or even anaphylaxis

8. d. Monocytes Larger than other leukocytes (15 - 20 um). They migrate to specific tissues (liver, spleen, lungs, lymph nodes) and stay there for prolonged periods of time (months, years). When activated, they secrete interleukin-1,2,4,5 (molecules that signal the production of lymphocytes, as well as inducing fever)

9. Lymphocytes: i. B cells: when activated, they become plasma cells, which produce specific antibodies. ii. T cells: “natural killer cells”. They attach to foreign cells that have specific proteins (antigens) in their membranes and produce lysis. This is a problem for transplants, immuno compatibility of tissues.

10. 3.Plasma: This is the solvent/carrier. Just water with different materials dissolved in it: Electrolytes, proteins, lipids, carbohydrates, amino acids, gasses (O2, CO2, N2), hormones, vitamins, antibodies Organs that maintain their concentrations: liver, kidneys, lungs, endocrine glands. Note these: Glucose: needed for ATP production. Albumin: maintains osmotic pressure. Edema without it. complement: a set of proteins that promotes -chemotaxis of leukocytes to area of infection/injury -opsonization. -release of anaphylotoxins (increase vascular permeability) -Disruption of some foreign cell membranes.

12. Antibodies ( = immunoglobulins): their job is to bind to antigens (bad guys) anaphylaxis.

13. Antigen + antibody  immune complex (non-covalent bonds) “agglutination” : a bunch of antibodies stick to something that has antigents on its surface. They all stick to each other as well. “opsonization” : the antibodies enhance phagocytosis by leukocytes. Kind of a “targeting system”

14. Antibody formation steps: 1-antigen taken up by monocytes 2- at the spleen, and lymph nodes: B-lymphocytes step production of the right antibody 3 – in the presence of interleukin-4,5 (released by T helper lymphocytes), the right kind of B-lymphocytes proliferate and go out into the lymph  blood stream. 4 – B-lymphocytes secrete lots more antibodies

15.  Small (2-4 um) they bud from “megakaryocytes” (large multi- nuclear cells in the bone marrow).  Many are sequestered in spleen for future usage.  Exterior coat = ”glycocalyx”. Glycoproteins, proteins, receptors Unit membrane. Contains enzymes for production of outer layer molecules, actin, myosin…etc. for structure.

17. Some Clotting triggers: Von Willbrand Factor (vascular) Hageman Factor (reacts with negatively charged surfaces) Thrombin (formation of fibrin) Inhibitors: heparin, aspirin

18. Example of Platelets in action: consider endothelial cell disruption (there are other clotting triggers too -): 1. platelets stick to collagen in the presence of spilled “Von Willbrand factor”. (complex biochemistry) 2. Platelets grow spiky pseudopods (=spicules) out. Povides structure, and traps serum to help form a plug. 3. Discharge of granules contents: triggers release of thrombin from endothelium Thrombin attracts and promotes the binding of more platelets. Note this is a very complex chain of events that we won’t cover. fibronectin and thrombonectin serveas glue. [change in your notes]

21. Hematopoiesis: Generation of blood cells happens in the bone marrow. (fetus and infant produce cells in the spleen and liver too, but eventually that shifts completely to the marrow). Stem cells:  Totipotent: completely undifferentiated, could turn into anything.  Pluripotent: could still become several different cells  committed cells environmental conditions determines the differentiation of the stem cells: hormones (erythropoietin), presence of antibodies, …

23. Note: Lymphocytes can also reproduce themselves (not just differentiation!) at the spleen and lymph nodes. Platelets are formed by megakaryocytic cells breaking up into smaller cells.