Physical Characteristics of Blood
• Thicker (more viscous) than water and flows more slowly
than water
• Temperature of 100.4 degrees F
• pH 7.4 (7.35-7.45)
• 8 % of total body weight
• Blood volume
– 5 to 6 liters in average male
– 4 to 5 liters in average female
– hormonal negative feedback systems maintain constant blood
volume and osmotic pressure
Blood components
• 55% = plasma: mainly water
– 7 to 8% dissolved substances (sugars, amino acids, lipids & vitamins), ions,
dissolved gases, hormones
– most of the proteins are plasma proteins: provide a role in balancing osmotic
pressure and water flow between the blood and extracellular fluid/tissues
– loss of plasma proteins from blood – decreases osmotic pressure in blood and
results in water flow out of blood into tissues  swelling
– most common plasma proteins: albumin, globulins, clotting proteins (fibrin)
Blood: Cellular elements
• 45% of blood is the cellular elements or formed elements
• 99% of this (44.55% of total blood) is erythrocytes or RBCs
– formed by differentiation of hematopoietic stem cells (HSCs) in the red bone
marrow of long bones and pelvis – makes about 2 million per second!
– made from an immature cell = reticulocyte
– as they mature in the marrow they lose most organelles and its nucleus
– lives only about 120 days – destroyed by the liver and spleen
– liver degrades the hemoglobin to its globin component and the heme is
degraded to a pigment called bilirubin - bile
– Iron(Fe+3)
•
•
•
•
transported in blood attached to transferrin protein
stored in liver, muscle or spleen
attached to ferritin or hemosiderin protein
in bone marrow being used for hemoglobin synthesis
-1% found in the Buffy coat :
-leukocytes (WBCs) and platelets
(thromobocytes)
-neutrophils: phagocytic properties
-release agents which destroy/digest
bacteria
-eosinophils: parasitic defense cells
-also involved in the allergic response
-release histaminase to slows down
inflammation caused by basophils
-basophils: release heparin, histamine &
serotonin
-heighten the inflammatory response and
account for hypersensitivity (allergic)
reaction
-monocytes: enter various tissues and
differentiate into phagocytic macrophages
-lymphocytes: T and B cells
Hematopoiesis
HSC
Hematocrit
• Percentage of blood occupied by cells
– female normal range
• 38 - 46% (average of 42%)
– male normal range
• 40 - 54% (average of 46%)
• testosterone
• Anemia
– not enough RBCs or not enough hemoglobin
• Polycythemia
– too many RBCs (over 65%)
– dehydration, tissue hypoxia, blood doping in
athletes
Blood Groups and Blood
Types
• RBC surfaces are marked by genetically
determined glycoproteins & glycolipids
– agglutinogens or isoantigens
– distinguishes at least 24 different blood groups
• ABO, Rh, Lewis, Kell, Kidd and Duffy systems
RH blood groups
• Antigen was discovered in blood of Rhesus monkey
• People with Rh agglutinogens on RBC surface are Rh+.
Normal plasma contains no anti-Rh antibodies
• Antibodies develop only in Rh- blood type & only with
exposure to the antigen
– transfusion of positive blood
– during a pregnancy with a positive blood type fetus
• Transfusion reaction upon 2nd exposure to the antigen
results in hemolysis of the RBCs in the donated blood
Hemolytic Disease of
Newborn
• Rh negative mom and Rh+ fetus will have mixing of blood at birth
• Mom's body creates Rh antibodies unless she receives a RhoGam shot soon after
first delivery
– can lead to miscarriage or spontaneous abortion of future Rh+ children
– RhoGam binds to loose fetal blood and removes it from body before she reacts
• In 2nd child, hemolytic disease of the newborn may develop causing hemolysis of
the fetal RBCs
•
Symptoms
– oxygen-carrying capacity of blood is reduced
– fatigue, cold intolerance & paleness
Anemia
• lack of O2 for ATP & heat production
•
Types of anemia
– iron-deficiency = lack of absorption or loss of iron
• type of nutritional anemia
• failure to take in essential raw ingredients not made by the body
– pernicious = lack of intrinsic factor for vitamin B12 absorption from the digestive
tract
• B12 is essential for normal RBC formation and maturation
• binding of B12 to intrinsic factor allows its absorption
• intrinsic factor – synthesized by the small intestine
– hemorrhagic = loss of RBCs due to bleeding (ulcer)
– hemolytic = defects in cell membranes cause rupture
• rupture of too many RBCs by external factors such as malaria (normal RBCs) or genetic
disorders like sickle cell anemia (defective RBCs)
– thalassemia = hereditary deficiency of hemoglobin
– aplastic = destruction of bone marrow (radiation/toxins)
• failure of the bone marrow to produce enough RBCs
• may selectively destroy the ability to produce RBCs only
• but may also destroy the myeloid stem cells – affect WBCs and platelets
Sickle-cell Anemia (SCA)
• Genetic defect in hemoglobin molecule
(Hb-S) that changes 2 amino acids in the
globin protein
– at low very O2 levels, RBC becomes deformed
by changes in hemoglobin molecule within the
RBC
• sickle-shaped cells do not pass through
capillaries well and get stuck = causing
occlusions and decreased blood flow to organs
• also rupture easily = causing anemia & clots
• Found among populations in malaria belt
– Mediterranean Europe, sub-Saharan Africa &
Asia
• Person with only one sickle cell gene
– increased resistance to malaria because RBC
Blood Clotting
– in a test tube blood separates into liquid (serum) and a clot of
insoluble fibers (fibrin) in which the cells are trapped
– in the body the clot “plugs” damaged blood vessels and initiates
healing
– ultimate step is conversion of fibrinogen (soluble plasma protein)
into insoluble fibrin
• Substances required for clotting are Ca+2, enzymes
synthesized by liver cells (clotting factors and plasma
proteins) and substances released by platelets or
damaged tissues
– thrombin – released by damaged cells, catalyzes the conversion of
fibrinogen to fibrin
– 12 clotting factors involved
• Clotting is a cascade of reactions in which each clotting
factor activates the next in a fixed sequence resulting in the
formation of fibrin threads
– prothrombinase & Ca+2 convert prothrombin into thrombin
– thrombin converts fibrinogen into fibrin threads
Overview of the Clotting Cascade
-may be triggered through two possible
paths
1. extrinsic pathway
2. intrinsic pathway
-both pathways result in the release and
activation of specific clotting factors
-either path leads to activation of the
common pathway
-common pathway results in the formation of
prothrombinase (clotting factors X and V)
-prothrombinase activates thrombin
-thrombin cleaves fibrinogen to form fibrin
The Body’s Response to Infection: The
Immune System
• Three lines of
defense
The Body’s Response to Infection:
First Line of Defense
• 1. Skin
– Sheds, takes pathogens with it
– Has low pH, repels microorganisms
– Glands in skin secrete chemicals to slow bacterial
growth
• 2. Mucous membranes
– Mucous traps pathogens
– Can be sneezed, coughed away
The Body’s Response to Infection:
Second Line of Defense
• 1. White blood cells production
• A.: macrophages and other phagocytes
– Engulf and digest invasive organisms
– Also digest old red blood cells and cellular debris
– Can release chemicals to stimulate production of more white
blood cells – like T and B cells
• B. White blood cells: natural killer cells
– Attack tumor cells and virus-infected cells
– Release chemicals that break apart the cell membranes of
infected cells or tumor cells
The Body’s Response to Infection: Second
Line of Defense – Inflammation
• 2. Inflammation: response which produces
redness, warmth, swelling, and pain
– After tissue injury, damaged cells release histamine
– Histamine causes vasodilation which increases blood
flow
• this will increase more WBCs into the infected area
• brings more O2 and nutrients
– BUT also brings in more fluid – some fluid gets
pushed out into the surrounding tissues = Swelling
The Body’s Response to Infection:
Second Line of Defense – Defensive Proteins
• 3. Interferons are produced by infected cells
– bind to healthy cells
– stimulate production of anti-viral chemicals
• 4. Complement proteins are made in response
to inflammation and infection
– are a class of about 20 different proteins
– can coat surface of bacteria to facilitate phagocytosis
– can make holes in bacterial membrane  BOOM!
The Body’s Response to Infection:
Second Line of Defense – Fever
• 5. Fever – temperature above range of 97-99º F
– macrophages can release pyrogens
• which causes temperature of tissue to increase
– increased temperature inhibits bacterial growth
– increases metabolism of healthy cells – promotes
mitosis and tissue repair
– large-scale production of pyrogens can increase
overall body temperature = Fever
– also increases the efficiency of immune cells
The immune system
 Cells of the immune cells (macrophages, T cells, B cells)
are found in specific locations called lymphatic tissues
The Body’s Response to Infection:
Third Line of Defense – Lymphocytes
• Lymphocytes are a specific defense because they recognize specific antigens
– antigen = cell-surface protein that identifies the type of cell bearing it
•
also distinguishes it from antigens in another organism
• when your immune system is developing – your lymphocytes learns what
antigens belong to you and what don’t
– develop self-tolerance
• examples of non self-tolerant, foreign antigens = proteins found on or in viruses,
bacteria, fungi, protozoans and worms.
• Lymphocytes travel throughout the body in spaces between the cells and are
carried in the blood and lymphatic system.
The Lymphatic System
• Lymphocytes travel throughout the body
in spaces between the cells and are
carried in the blood and lymphatic
system.
• the lymphatic system = system of
lymphatic vessels + lymph nodes +
lymphatic tissues (spleen, thymus,
tonsils) that filter lymph and circulate
WBCs
• lymph = yellow-colored fluid that is
produced from your blood plasma
–
–
produced when plasma filters out of
your blood and into your tissues
some of that filtrate becomes lymph
The Lymphatic System
•
•
•
•
•
Lymph comes from your blood plasma but is returned
to you blood stream
along the way it flows through lymph nodes which
house lymphocytes and macrophages
these immune cells clean the lymph of bacteria
so what gets returned to your blood is cleaned
lymph is the way we “launder” our blood
http://www.niaid.nih.gov/topics/immuneSystem/Pages/structureImages.
aspx
The Body’s Response to Infection:
Third Line of Defense – Lymphocytes
• Two types of Lymphocytes
– A. T cells
– B. B cells
Lymphocytes
• Lymphocytes are produced from stem cells in the red bone
marrow.
• they are named by the location where they were first identified
• B cells develop in the
bone marrow
• T cells
develop in the thymus
– thymus disappears over time
T and B Lymphocytes
• B cells
– Recognize small organisms such as bacteria by producing antibodies
– antibodies = small proteins that bind foreign antigens and target the foreign
cell for destruction by the host’s immune system
– can respond to viruses if “helped” by T cells

Antibody:
 abbreviated as Ig
 made up of four protein chains
 two light chains
 two heavy chains – determine the type of antibody
 “ends” of the antibody are specific for the foreign
antigen = “Antigen-binding Site”
T and B Lymphocytes
• T cells
– Respond to larger organisms (e.g. fungus), viruses, and body
cells that have gone awry (e.g. tumor cells)
• also attack transplanted tissues!
• if they attack normal cells = Auto-immune disease
– Attack the antigen-bearing cell directly by secreting chemicals
that kill it
– help B cells and “teach” them what antibodies to make
• can bind a foreign protein and then interact with a B cell
• B cell then makes antibodies to that foreign protein
T and B Lymphocytes
• B and T cells display cell-surface proteins that bind to foreign antigens
– called antigen receptors
– once they bind the T and B cells are called “activated”
– activated T cells “help” B cells by physically binding them
– the B cell then begins to make antibodies
 B and T cells have a Memory

once the infection is cleared,
there are a small number of T
and B cells that “remember” the
infection

will become activated if the
foreign antigen re-appears

faster activation than the 1st time
Types of Immunity: Antibody and CellMediated Immunity
• B cell mediated immunity is called Antibody
mediated immunity
• B cells exposed to foreign antigens rapidly
divide = clonal expansion
• most B cells develop into plasma cells that
make the antibodies
• Rest of B cells become memory cells to
provide long term immunity
Antibody and Cell-Mediated Immunity
• T cell mediated immunity is called Cell-mediated immunity
• T cells divide exposed to foreign antigens divide and develop
into different types of cells
– depends on the foreign antigen
– if it’s a bacterial antigen  helper T cells
• help B cells make antibodies
– if it’s a viral or tumor antigen  cytotoxic T cells
• secrete chemical to directly kill the pathogen
• e.g. interferons
• some stay as memory T cells
Cell-Mediated Immunity

T cells need “help” learning what a foreign antigen is

the are “presented” the foreign antigen by another cell = Antigen-Presenting cell

the APC internalizes the foreign invader and “displays” foreign antigens on its surface

the T cell binds the APC and “learns” what the foreign antigen looks like

the T cell is now activated and can develop either into helper or cytotoxic T cells
foreign cell
foreign antigen
secrete chemicals called
interleukins that enhance
B cell and T cell activity
also help B cells
to make antibodies
Types of Immunity
• immunity can also be classified into:
• Passive Immunity – short-term immunity, lasts as long
as the antibodies are in bloodstream.
– can be passed on via fluids
– e.g. antibodies found in breast milk
• Active Immunity – long-term, caused by exposure to
antigen and production of B and T cells.
– basis for immunity from vaccinations
Vaccinations
• Vaccinations attempt to take advantage of longterm immunity through exposure to parts of
antigens.
– Produces population of memory cells
– Some antigens, such as flu, mutate quickly and
require frequent vaccinations
– Some antigens are difficult to make vaccines for
The Body’s Response to Infection:
The Immune System – Allergy
• Allergy – immune response that occurs even though no
pathogen is present
– Body reacts to a non-harmful substance as if it were
pathogenic
• called an allergen
– immune cells called mast cells produce large amounts of
histamine and leukotrienes  inflammation
– Common allergies include ragweed pollen and peanuts
– Asthma might be caused by allergy