Functions of Blood: 1 - Transportation:

o oxygen & carbon dioxide o nutrients o waste products (metabolic wastes, excessive water, & ions)

2 - Regulation - hormones & heat (to regulate body temperature)

3 - Protection - clotting mechanism protects against blood loss & leucocytes provide immunity against many disease-causing agents

Components of Blood - average adult has about 5 liters (about 5 qts) 

1 - Formed elements: o Red blood cells (or erythrocytes) o White blood cells (or leucocytes) o Platelets (or thrombocytes)

           2 - Plasma = water + dissolved solutes

Red Blood Cells (or erythrocytes): 1 - biconcave discs

2 - lack a nucleus & cannot reproduce (average lifespan = about 120 days)

3 - transport hemoglobin (each RBC has about 280 million hemoglobin molecules)

4 - Typical concentration is 4-6 million per cubic mm (or hematocrit [packed cell volume] of about 42% for females & 45% for males)

5 - contain carbonic anhydrase (critical for transport of carbon dioxide)

Determining the hematocrit

Erythropoiesis = formation of erythrocytes

the body must produce about 2.5 million new RBCs every second in adults, erythropoiesis occurs mainly in the marrow of the sternum, ribs,

vertebral processes, and skull bones begins with a cell called a hemocytoblast or stem cell (below) rate is regulated by oxygen levels:

o hypoxia (lower than normal oxygen levels) is detected by cells in the kidneys

o kidney cells release the hormone erythropoietin into the blood o erythropoietin stimulates erythropoiesis by the bone marrow

Source: http://greenfield.fortunecity.com/rattler/46/haemopoiesis.htm

Hemoglobin

composed of globin (made up of 4 highly folded polypeptide chains) + 4 heme groups (with iron)

each molecule can carry 4 molecules of oxygen called oxyhemoglobin when carrying oxygen & called reduced hemoglobin when

not carrying oxygen can also combine with carbon dioxide & helps transport carbon dioxide from the

tissues to the lungs

White blood cells (or leucocytes or leukocytes):

have nuclei & do not contain hemoglobin typical concentration is 5,000 - 9,000 per cubic millimeter types of WBCs:

o granular white blood cells include: neutrophils (50 - 70% of WBCs) eosinophils (1 - 4%) basophils (less than 1%)

o agranular (or non-granular) white blood cells include: lymphocytes (25 - 40%)

monocytes (2 - 8%)

Granular white blood cells contains numerous granules in the cytoplasm, & their nuclei are lobed. Agranular white blood cells have few or no granules in the cytoplasm & have a large spherical nucleus. Granular white blood cells are produced in the bone marrow, while agranular white blood cells are produced in lymph tissue, e.g., Lymph nodes (specialized dilations of lymphatic tissue which are supported within by a meshwork of connective tissue called reticulin fibers and are populated by dense aggregates of lymphocytes and macrophages).

The primary functions of the various white blood cells are:

Neutrophils - phagocytosis (bacteria & cellular debris); very important in inflammation

Eosinophils - help break down blood clots & kill parasites

Basophils - synthesize & store histamine (a substance released during inflammation) & heparin (an anticoagulant); functions(s) remain unclear

Monocytes - phagocytosis (typically as macrophages in tissues of the liver, spleen, lungs, & lymph nodes)

Lymphocytes - immune response (including production of antibodies)

Some important characteristics of White Blood Cells (particularly neutrophils):

1 - phagocytic 2 - capable of diapedesis (also called extravasation)

3 - capable of ameboid movement (check out Ameboid Movement - Amoeba)

4 - exhibit chemotaxis (attracted to certain chemicals, such as those released by damaged cells)

Platelets (or thrombocytes)

1 - formed in the bone marrow from cells called megakaryocytes

2 - have no nucleus, but can secrete a variety of substances & can also contract (because they contain actin & myosin)

3 - normal concentration in the blood is about 250,000 per cubic millimeter

4 - remain functional for about 7 - 10 days (after which they are removed from the blood by macrophages in the spleen & liver)

5- play an important role in hemostasis (preventing blood loss)

Plasma:

1 - Water - serves as transport medium; carries heat

2 - Proteins

Albumins o 60-80% of plasma proteins o most important in maintenance of osmotic balance o produced by liver

Globulins o alpha & beta

some are important for transport of materials through the blood (e.g., thyroid hormone & iron)

some are clotting factors produced by liver

o gamma globulins are immunoglobulins (antibodies) produced by lymphocytes

Fibrinogen o important in clotting o produced by liver

Twenty-two proteins constitute 99% of the protein content of plasma (Tirumalai et al. 2003).

3 - Inorganic constituents (1% of plasma) - e.g., sodium, chloride, potassium, & calcium

4 - Nutrients - glucose, amino acids, lipids & vitamins

5 - Waste products - e.g., nitrogenous wastes like urea

6 - Dissolved gases - oxygen & carbon dioxide

7 - Hormones

Hemostasis - prevention of blood loss from broken vessel

1 - Vascular spasm - vasoconstriction of injured vessel due to contraction of smooth muscle in the wall of the vessel. This 'spasm' may reduce blood flow & blood loss but will not stop blood loss.

2 - Formation of a platelet plug - platelets aggregate at the point where a vessel ruptures. This occurs because platelets are exposed to collagen (a protein found in the connective tissure located just outside the blood vessel). Upon exposure to collagen, platelets release ADP (adenosine diphosphate) & thromboxane. These substances cause the surfaces of nearby platelets to become sticky and, as 'sticky' platelets accumulate, a 'plug' forms.

3 - Blood coagulation (clotting):

Used with permission of Michael W. King, Ph.D / IU School of Medicine  

The result of all of this is a clot - formed primarily of fibrin threads (or polymers), but also including blood cells & platelets.

Blood clots in the right places prevent the loss of blood from ruptured vessels, but in the wrong place can cause problems such as a stroke (see below under inappropriate clotting).  

Clot retraction:

"tightening" of clot contraction of platelets trapped within clot shrinks fibrin meshwork, pulling edges

of damaged vessel closer together

Over time (with the amount of time depending on the amount of damage), the clot is dissolved and replaced with normal tissue.

Fibrinolysis:

dissolution of clot mechanism = plasminogen (a plasma protein) is activated by many factors &

becomes PLASMIN. Plasmin then breaks down fibrin meshwork & phagocytic WBCs remove products of clot dissolution

Inappropriate clotting:

thrombus - clot formed in an intact vessel, possibly due to: o roughened vessel walls (atherosclerosis; see normal & occluded coronary

arteries below) o slow-moving blood (e.g., in varicose veins) = small quantities of fibrin

form & accumulate

embolus - 'moving' clot

Source: http://www.ors.od.nih.gov/medart/portfolio/Donny/embolus.html

Excessive bleeding:

Hemophilia o genetic 'defect' o inability to produce certain factor(s)

Thrombocytopenia o abnormally low platelet count o most persons have idiopathic thrombocytopenia (= unknown cause) while

in others it's an autoimmune disease

CELLS OF THE IMMUNE RESPONSEImmune responsive cells can be divided into five groups based on i) the presence of specific surface components and ii) function: B-cells (B lymphocytes), T-cells (T lymphocytes), Accessory cells (Macrophages and other antigen-presenting cells), Killer cells (NK and K cells), and Mast cells. Some of the properties of each group are listed below.

Cell groupSurface components

Function

B-lymphocytes Surface immunoglobulin (Ag recognition)

Immunoglobulin Fc receptor

Class II Major Histocompatability Complex (MHC) molecule (Ag presentation)

Direct antigen recognition

Differentiation into antibody-producing plasma cells

Antigen presentation within Class II MHC

T-lymphocytes CD3 molecule

T-cell receptor (TCR, Ag recognition)

Involved in both humoral and cell-mediated responses

Helper T-cells (TH) CD4 molecule Recognizes antigen presented within Class II MHC

Promotes differentiation of B-cells and cytotoxic T-cells

Activates macrophages

Suppressor T-cells (TS)

CD8 molecule Downregulates the activities of other cells

Cytotoxic T-cells (CTL)

CD8 molecule Recognizes antigen presented within Class I MHC

Kills cells expressing appropriate antigen

Accessory cells Variable Phagocytosis and cell killing

Macrophages Immunoglobulin Fc receptor

Complement component C3b receptor

Class II MHC molecule

Bind Fc portion of immunoglobulin (enhances phagocytosis)

Bind complement component C3b (enhances phagocytosis)

Antigen presentation within Class II MHC

Secrete IL-1 (macrokine) promoting T-cell differentiation and proliferation

Can be "activated" by T-cell lymphokines

Dendritic cells Class II MHC molecule

Antigen presentation within Class II MHC

Polymorphonuclear cells (PMNs)

Immunoglobulin Fc receptor

Complement component C3b receptor

Bind Fc portion of immunoglobulin (enhances phagocytosis)

Bind complement component C3b (enhances phagocytosis)

Killer cells Variable Direct cell killing NK cells Unknown Kills variety of

target cells (e.g. tumor cells, virus-infected cells, transplanted cells)

K cells Immunoglobulin Fc receptor

Bind Fc portion of immunoglobulin

Kills antibody-coated target cells (antibody-dependent cell-mediated cytotoxicity, ADCC)

Mast cells High affinity IgE Fc receptors

Bind IgE and initiate allergic responses by release of histamine

LYMPHOID TISSUES

Primary Secondary(Responsible for maturation of Ag-

reactive cells)(Sites for Ag contact and response)

Thymus(T-cell

maturation)

Bone marrow

Lymph nodes

Spleen

(T-cell maturation) (B-cell maturation)

(Expansion of lymphatic system,

separate from blood circulation.

Deep cortex harbors mostly T-cells, superficial cortex harbors mostly B-cells)

(Similar to lymph nodes but part of blood circulation. Collects blood-

borne Ags

Immunoglobulins

Immunoglobulins generally assume one of two roles: immunoglobulins may act as i) plasma membrane bound antigen receptors on the surface of a B-cell or ii) as antibodies free in cellular fluids functioning to intercept and eliminate antigenic determinants; in either role, antibody function is intimately related to its structure.

BASIC IMMUNOGLOBULIN FUNCTION

Antibodies function in a variety of ways designed to eliminate the antigen that elicited their production. Some of these functions are independent of the particular class (isotype) of immunoglobulin. These functions reflect the antigen binding capacity of the molecule as defined by the variable and hypervariable (idiotypic) regions.

For example, an antibody might bind to a toxin and prevent that toxin from entering host cells where its biological effects would be activated.

Similarly, a different antibody might bind to the surface of a virus and prevent that virus from entering its host cell.

In contrast, other antibody functions are dependent upon the immunoglobulin class (isotype). These functions are contained within the constant regions of the molecule.

For example, only IgG and IgM antibodies have the ability to interact with and initiate the complement cascade. Likewise, only IgG molecules can bind to the surface of macrophages via Fc receptors to promote and enhance phagocytosis.

The following table summarizes some immunoglobulin properties.

Isotype StructurePlacental transfer

Binds mast cell

surfaces

Binds phagocytic

cell surfaces

Activates complement

Additional features

IgM - - - +First Ab in development and response.

IgD - - - - B-cell receptor.

IgG + - + +

Involved in opsonization and ADCC. Four subclasses; IgG1, IgG2, IgG3, IgG4.

IgE - + - -Involved in allergic responses.

IgA - - - - Two subclasses;

IgA1, IgA2. Also found as dimer (sIgA) in secretions.