Vascular Biology – 4blood and its components

• Disclaimer: this is a very broad topic and we won’t be able to get into it in depth.

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).

 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.

 a.      Neutrophils (granulocyte):  

can digest bacteria through use of hydrogen peroxide , free OH radicals, and oxidation.

Can live 4-5 days in extravascular space    

a.      Eosinophils (granulocyte):

similar to neutrophils. Involved in asthma, allergies. Can survive for weeks in the extravascular space

a.      Basophils (granulocyte)

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

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) 

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. 

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.

 

 

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

 

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”

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 

       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.

Some Clotting triggers:Von Willbrand Factor (vascular)Hageman Factor (reacts with negatively charged surfaces)Thrombin (formation of fibrin)

Inhibitors: heparin, aspirin

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]

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 cellsenvironmental conditions determines the differentiation of the stem cells: hormones (erythropoietin) , presence of antibodies, …

 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.