BIOM *3200–UNIT 4 BLOOD AND IMMUNITY

COURSELINK NOTES:
INTRODUCTION
By the end of this unit you should be able to:
1. Describe the role of the lymphatic system; lymphatic vessels and lymphoid tissue with
respect to lymph fluid and immunity;
2. Define the cellular and acellular constituents of the blood;
3. Identify constituents of innate and adaptive immunity;
4. Indicate the role of B-cells in humoral immunity and T-cells in cell mediated immunity;
and
5. Describe hemostasis.

THE LYMPHATIC SYSTEM

• The lymphatic system consists of organs and glands that produce and/or store cells, along
with a system of lymphatic vessels that connects them to the rest of the body
• The lymphatic vessels are closely associated with the circulatory system and absorb
excess interstitial fluid and transport this fluid (lymph) to ducts that drain it back into the
blood stream (veins)
• The glands and organs (ex. lymph nodes, thymus, spleen, tonsils) of the lymphatic system
also facilitate immune defense from disease-causing agents called pathogens
 They produce lymphocytes, that are white blood cells involved in the immune
response
Lymphatic Vessels
o The lymphatic system begins in microscopic,
blind-ended tubes located in spaces between
cells throughout the entire body termed
lymphatic capillaries
o They are composed of a flattened layer of
endothelial cells attached to a basement
membrane
o This configuration confers lymphatic capillaries
with an extremely permeable surface that
facilitates water, ions, peptide and proteins
entry from the interstitial spaces
o Once interstitial fluids enter the lymphatic
capillaries, it becomes lymph or lymph fluid
and flows into larger lymphatic vessels
o Lymphatic vessels are continuous with
lymphatic capillaries and are lined by flattened
endothelial cells
o Two addition layers constitute the lymphatic
vessel:
1. A middle smooth muscle cell
2. An outer connective tissue layer
o These lymphatic vessels transfer lymph fluid towards the heart and combine with other
lymphatic vessels, draining larger and larger areas of the body of lymph fluid
o Lymphatic vessels drain into large lymphatic ducts and return lymph fluid directly into
venous circulation
o The largest collecting duct is the thoracic duct that drains the abdomen and enters
systemic circulation at the left subclavian vein
o Lymphatic vessels and ducts are thinned walled and difficult to dissect grossly
o Lymphatic vessels, like veins, contain one-way valves composed of endothelial cells that
ensures one-way flow towards the heart
• Lymph flows through the lymphatic vessels via a squeezing action forcing the lymph
one-way through the lymphatic system similar to squeezing toothpaste out of its tube
• The middle smooth muscle layer of vessels can provide the squeezing pressure to move
lymph, but to ensure efficient flow against gravity, two additional methods are required:
1. The skeletal muscle
2. The respiratory pumps
• The thin-walled lymphatic vessels lie between large skeletal muscle that upon
contraction, press on lymphatic vessels compressing them
• This compression forces the lymph fluid through the one-way valve system and
'massages' the lymph fluid back towards systemic circulation
• The respiratory pump moves lymph fluid during inspiration when intrathoracic pressure
drops and intraabdominal pressure increases
• These combined actions are due to the movement of the diaphragm, and forces lymph
fluid from vessels in the abdomen (where pressure is the highest) and into the thoracic
lymph vessels (where pressure is lowest), thus efficiently moving lymph fluid against
gravity
Lymph Nodes
o Along the length of lymphatic vessels are discrete bodies of 1-25 mm in length called
lymph nodes
o Each lymph node has multiple afferent vessels, which enter separately on the surface, and
fewer efferent lymphatic vessels that drain the node
o Fewer efferent lymphatic vessels ensure the lymph fluid will slowly filter through the
inside of the lymph node, which consists of an outer cortex containing germinal centers
and an inner medulla
o The germinal centers are rich in immune cells (B cells), whereas macrophages and T-
cells populate the medullary areas
o The lymph node slowly filters lymph through the node where it comes into contact with
multiple types of immune cells
o If immune cells of a lymph node identify pathogens such as bacteria, viruses or parasites,
it is quickly removed from the lymph fluid
o Lymphocytes can also divide in lymph nodes to facilitate an immune response during an
infection or cancer metastasis
o Thus, lymph nodes are routinely inspected for signs of infection or staging cancer
metastasis
o A common lymph node that becomes inflamed and swollen during throat and respiratory
infections are the cervical lymph nodes located throughout the neck region
• The thymus and spleen are two additional organs that function in a similar capacity as
lymph nodes
• The thymus is located in young mammals in the cranial portion of the thoracic cavity
(mediastinum)
• After puberty the thymus shrinks (atrophies) over the lifespan of the mammal so that in
late adulthood, the thymus is replaced by connective and adipose tissues
• The thymus is critical for the formation of T-cells
• The spleen is located in the upper left abdominal quadrant in humans, lateral to the
stomach
• It is the largest of all lymphoid organs and unique in that it contains blood as well as
lymph
• The interior of the spleen consists of white pulp packed with lymphocytes and
surrounding red pulp that contains red blood cells (RBCs)
• The spleen functions similar to a lymph node, by filtering blood
• Systemic blood enters the spleen by the splenic artery, filters through the white pulp and
exits via the splenic vein exposing pathogens to immune cells
• Forcing red blood cells through small spaces in red pulp causes old RBCs to rupture,
ensuring RBCs maintain a lifespan of approximately 120 days
• Immune cells in the area to prevent the accumulation of cellular debris by quickly
engulfing ruptured fragments of RBCs
 • The spleen also acts as a reservoir for RBCs, which can contract, and release RBCs
during times when the oxygen carrying capacity of blood needs to be increased
 Ex. major external haemorrhage, altitude sickness and exercise

BLOOD
o A liquid tissue that transports nutrients, oxygen, wastes, carbon dioxide, hormones,
growth factors, immune cells and heat throughout the body
o Along with the heart and blood vessels, the blood forms the cardiovascular system that
links all parts of the mammal together
o Blood consists of 45% solid portion (formed elements) and 55% liquid portion termed
plasma
o The formed elements consist of red blood cells
(RBCs), platelets and white blood cells
o The vast majority of cells in blood are the RBCs,
which comprise ~95% of all the cells
o The hematocrit refers to the percentage of volume of
blood occupied by cells (often defaulted to RBCs)
o The remainder is composed of platelets (5%) and white
blood cells (<1%)
o The plasma is a complex mixture of water, amino
acids, proteins, carbohydrates, lipids, vitamins,
hormones, electrolytes and cellular wastes
o When plasma is separated by centrifugation it forms a
straw-coloured upper layer
Red Blood Cells (RBCs)
• RBCs or erythrocytes exhibit a characteristic biconcave shape that confers various
functional advantages:
1. Increases the surface area to allow for more oxygen binding
2. Haemoglobin molecules are closer to the cell surface, which aids in oxygen
binding
3. Confers the ability to bend and squeeze through tight spaces like capillary
networks
• RBCs are packed with haemoglobin, which is a large, oxygen-binding protein that
provides RBCs with their characteristic red colour
• When oxygen is bound to haemoglobin (oxyhemoglobin) it exhibits a rich red colour,
when oxygen is released (deoxyhemoglobin) blood becomes darker
 This difference in colour allows for the differentiation between systemic arterial
blood and venous blood
• RBCs are produced in the red bone marrow of mammals through a process called
erythropoiesis
• Red bone marrow is located in the long bones of mammals and responds to the hormone
erythropoietin (EPO) by increasing the rate of RBC production
• EPO is released in the kidney in response to a decreased oxygen tension of the blood
• Erythropoiesis consists of a step-wise differentiation of a stem cell termed the
erythroblast
• During an early step of RBCs development, the nucleus is extruded and thus all mature
RBCs are anucleated
• As a result, mature RBCs have a finite
lifespan of 120 days and rely entirely on
glycolysis for ATP production
• Old RBCs become stiff and circulation
through the spleen and liver can cause brittle
RBCs to lyse, ultimately removing them
from circulation
• Obligate use of glycolysis for ATP
production maximizes oxygen-carrying
capabilities of RBCs as glycolysis is
anaerobic (doesn’t require oxygen)
Platelets
o Platelets or thrombocytes are small, fragments of cells which are derived from the larger
megakaryocyte
o These small, cytoplasmic fragments contain numerous factors that facilitate thrombus or
blood clot formation
o When platelets come into contact with damaged inner endothelial linings of blood
vessels, they activate by changing shape and become more stellate (star-like)
o The morphology change makes them more sticky and they begin to clump together
forming a platelet plug in an attempt to limit blood loss to the exterior environment
 o Activated platelets also release various factors to facilitate thrombus formation and
vascular repair including:
▪ Platelet derived growth factor (PDGF)
▪ Vascular endothelial growth factor (VEGF)
▪ Transforming growth factor beta (TGF-β)
▪ Serotonin
o Platelets are anucleated and have an average lifespan of ten days

White Blood Cells

• White blood cells (WBCs), or leukocytes, composed a group of cells that protect against
infectious diseases
• Leukocytes differ from RBCs and platelets as they are relatively larger cells, are
nucleated and few in number
• They can be broken down into two general categories based on their cytoplasmic
morphology:
 Granulocytes
 Agranulocytes
• Granulocytes contain characteristic granules in their cytoplasm and include:
 Neutrophils
 Eosinophils
 Basophils
• Agranulocytes lack a granular cytoplasm and
include:
❖ Monocytes
❖ Lymphocytes
 o WBCs are produced in bone marrow from stem cell populations (myeloid and lymphoid
stem cells) under the influence of various growth factors including:
▪ Stem cell factor (SCF)
▪ Granulocyte-macrophage SCF (GM-SCF)
▪ Granulocyte SCF (G-SCF)
▪ Macrophage SCF (M-SCF)

• T and B lymphocytes are a subset of WBCs that are involved in specific immunity
• Specific immune involves the recognition of antigen, a substance that activates T and B
cells
• Often the specific part of the antigen is termed the epitope, and this binds to cellular
receptors located on the surface of the lymphocyte
• Common antigens include infectious bacteria, viral particles, toxins and cancer
• In contrast, the innate or non-specific immune system include general mechanisms for
immune defence and include:
 Mechanical barriers (skin)
 Chemical barriers (stomach juices)
 Inflammation, phagocytosis
 Fever
 Natural killer (NK) cells
• Antigen recognition is a complex procedure that requires processing by antigen
presenting cells (APCs)
 Ex. macrophages (located throughout the body, but are numerous in secondary
lymphoid tissue such as spleen and lymph nodes)
• APCs detect, engulf, digest and present antigens on their surface using a group of
proteins termed the major histocompatibility complex (MHC)
• The two types of MHC molecules are found throughout the mammalian body include:
 Class I MHC (which are found on all nucleated cells)
 Type II (which are only found on APCs)
• T-cells become activated upon binding to the antigen: MHC complex
• This type of immunity is termed "cell mediated" due to the cell to cell contacts T-cells
make with APCs
• The activation of T-cells not only requires proper antigen processing and presentation,
but also is specific to a particular antigen
• Thus, one T-cell will recognize only one antigen
[VIDEO]

o T lymphocytes can be categorized by receptors they express on the surface of the cells
and their mechanism of immunity
o Cytotoxic (Killer) T-cells, also termed CD8 T cells, proliferate when they are activated,
and bind to cancer cells or virally infected cells which display non-self antigens
o Once bound to the cells, they secrete perforin, a protein that produces holes in cells
causing the infected/damaged cells to undergo programmed cell death (apoptosis)
o These cytokines can activate other lymphocytes such as cytotoxic CD8 T cells and B
cells to mediate immunity
o The importance of CD4 T cells is illustrated in people who have acquired
immunodeficiency syndrome (AIDS)
o he human immunodeficiency virus (HIV) specifically targets the CD4 positive cell
population in HIV positive individuals and eventually prevents activation of CD8
positive T cells and B cells resulting in life-threatening immune deficiency

o B lymphocytes produce antibodies (Ab) or immunoglobulins in response to specific

antigen exposure and activation by T helper cells
o Upon activation, B cells proliferate then differentiate into plasma cells that produce 2,000
antibodies per second
o Once secreted, antibodies bind to their cognate antigen located on pathogens, which
facilitates destruction by agglutination, precipitation or neutralization
o As the antibodies that are secreted by activated B cells diffuse through bodily fluids, this
type of specific immunity is termed 'humoral immunity'
o Lymphocytes (both T and B cells) can remain dormant for years after the first or primary
exposure to an antigen
o Upon subsequent exposure to the same antigen at a later date (secondary exposure), the
memory lymphocytes can rapidly expand and produce a faster more efficient immune
response
Blood Plasma
• Blood plasma is the liquid portion of blood that suspends all of the formed elements
• It consists of approximately 92% of water, the rest comprised of various organic and
inorganic molecules
• Plasma proteins are abundant in plasma and contribute to the colloid osmotic pressure of
blood plasma
• Three major types of plasma proteins that are produced by the liver include:
1. Albumens
2. Globulins
3. Fibrinogen
• Albumens and globulins are important for transporting various molecules including free
fatty acids, hormones, drugs, fat-soluble vitamins and antibodies
• Blood gases are directly dissolved in plasma and major molecules include:
 Oxygen
 Carbon dioxide
 Nitrogen
• Nutrients like glucose must be maintained at precise levels to prevent life-threatening
homeostatic imbalances (hyper- and hypo-glycemia)
• plasma electrolytes must also be maintained at precise levels to prevent alterations in
resting membrane potentials of cells or pH of the blood
• Examples of important electrolytes include the following ions:
 Sodium (Na+)
 Potassium (K+)
 Magnesium (Mg2+)
 Calcium (Ca2+)
 Phosphate (PO4–)
  Sulphate (SO42–)
 Hydrogen (H+)
 Bicarbonate (HCO3–)
 Chloride (Cl-)

HOMEOSTASIS
o Hemostasis refers to the stopping of bleeding
o It is a process that attempts to avoid blood loss after vascular injury by vasospasm,
platelet plug formation and blood coagulation
o Damage to blood vessels causes smooth muscle contraction that results in the blood
vessels decreasing diameter of their lumens and ultimately decreasing blood flow
o This decrease blood flow at the site of severing or tearing limits the amount of blood loss
o The vessels remain constricted for a short period of time
o Fortunately, activated platelets release serotonin, which extends the vasospasm to allow
for effective thrombus formation
o These activated platelets release various growth factors (discussed above) and become
sticky forming a platelet plug
o This platelet plug may be enough to plug the bleeding, but often coagulation is needed to
stop most bleeds

o Coagulation is a biochemical process that produces blood clots or thrombi

o These thrombi are essentially meshwork of proteins that binds platelet plugs and blood
cells
o The meshwork is formed by fibrin, a sticky fibrous protein that is normally found in its
inactivated form fibrinogen
o The formation of active fibrin from its inactivate precursor form occurs through a
cleavage that is ultimately controlled by two pathways:
▪ The intrinsic pathway
▪ The extrinsic pathway
o These pathways are biochemical reactions that activate clotting factors that cascade in a
step-wise manner
o These clotting factors are also present in an inactivated form in the blood, produced
constitutively by the liver
o Once activated by the intrinsic or extrinsic pathways, they form a positive feedback loop,
which results in the rapid formation of a fibrin meshwork that traps platelets and blood
cells and facilitates hemostasis
o The intrinsic pathway begins with factors present within the blood
o Exposure of extracellular matrix outside the lumen of blood vessels to clotting factors
initiates this cascade
o The extrinsic pathway is triggered when damaged tissues release factors that initiate
coagulation
o Both pathways converge to one common pathway at the coagulation protein thrombin
o Both pathways also cleave the inactivate prothrombin into the active thrombin
o Activated thrombin cleaves fibrinogen to fibrin in the common pathway
o Once a clot is formed, the tissue repair pathways are initiated which include:
▪ Clot shrinkage
▪ Fibroblast infiltration
▪ Angiogenesis
o To ensure the clotting reaction does not spread systemically, fibrin can bind thrombin in
an attempt to limit the positive feedback loop
o Furthermore, basophils and mast cells involved in the tissue repair secrete the protein
heparin, which prevents the formation of thrombin and attempts to limit the size of blood
clot formation
o Once healing process is completed and the clot is no longer needed, plasmin becomes
activated from the inactivate plasminogen and breaks down the fibrin network through a
process called fibrinolysis
o Tissue plasminogen activator (tPA), urokinase and lysosomal enzymes are examples of
proteins that can activate plasminogen and begin the process of dissolving a blood clot