Transcript vasculature-lecture-4

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.
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.
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Have clearly defined nuclei.
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“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 multinuclear 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.
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Pluripotent: could still become several different cells

committed cells
environmental 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.