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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
o
o

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


kidneys
kidney cells release the hormone erythropoietin into the blood
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 RESPONSE


Immune 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 group
B-lymphocytes

Surface
components
Surface
immunoglobulin (Ag
recognition)
Immunoglobulin Fc
receptor

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

Antigen
presentation within
Class II MHC

CD3 molecule

T-cell receptor
(TCR, Ag
recognition)
CD4 molecule

Involved in both
humoral and cellmediated
responses

Recognizes antigen
presented within
Class II MHC
Promotes
differentiation of Bcells and cytotoxic
T-cells

T-lymphocytes

Helper T-cells (TH)

Function

Suppressor T-cells
(TS)

CD8 molecule

Cytotoxic T-cells
(CTL)

CD8 molecule

Direct antigen
recognition
Differentiation into
antibody-producing
plasma cells

Activates
macrophages
Downregulates the
activities of other
cells
Recognizes antigen
presented within
Class I MHC
Kills cells
expressing
appropriate antigen

Accessory cells

Macrophages

Variable

Immunoglobulin Fc
receptor
Complement
component C3b
receptor

Class II MHC
molecule

Dendritic cells

Class II MHC
molecule

Polymorphonuclear
cells (PMNs)

Immunoglobulin Fc
receptor

Complement
component C3b
receptor

Killer cells
NK cells

K cells

Phagocytosis and
cell killing
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
Antigen
presentation within
Class II MHC
Bind Fc portion of
immunoglobulin
(enhances
phagocytosis)

Bind complement
component C3b
(enhances
phagocytosis)

Variable
Unknown

Immunoglobulin Fc
receptor

Direct cell killing


Kills variety of
target cells (e.g.
tumor cells, virusinfected cells,
transplanted cells)
Bind Fc portion of
immunoglobulin

Mast cells

High affinity IgE Fc


receptors

Kills antibodycoated target cells


(antibodydependent cellmediated
cytotoxicity, ADCC)

Bind IgE and initiate


allergic responses
by release of
histamine

LYMPHOID TISSUES

Primary

Secondary

(Responsible for maturation of Agreactive cells)

(Sites for Ag contact and response)

Thymus
(T-cell
maturation)

(T-cell maturation)

Bone
marrow

Lymph
nodes

Spleen

(Expansion of
lymphatic system,
separate from blood (Similar to lymph
circulation. Deep
nodes but part of
(B-cell maturation)
cortex harbors
blood circulation.
mostly T-cells,
Collects bloodsuperficial cortex
borne Ags
harbors mostly Bcells)

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.
Binds
Binds
Placental
phagocytic Activates
Additional
Isotype Structure
mast cell
transfer
cell
complement features
surfaces
surfaces

IgM

First Ab in
development
and
response.

IgD

B-cell
receptor.

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

IgG

IgE

Involved in
allergic
responses.

IgA

Two
subclasses;

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