White blood cells

Part 2
outline
• White blood cell and differential count
• Reticuloendothelial system
• Platelet function.
• Coagulation and Fibrinolysis
• Immunity and immunodeficiency diseases and HIV

Please note that the following points on the slides are for guidance
purposes, you will need to attend lectures and carry out further reading
as well as assignments for a satisfactory understanding of the course.
White blood cell and differential count
• White blood cells are cellular part of the blood that are concerned
with immunity or body defense.
• White blood cells (Leukocytes) can be subdivided in A. Granulocytes
and B. Agranulocytes
• They are formed partially in the bone marrow (granulocytes and
monocytes) and partially in the lymph tissues (lymphocytes and B
cells)
Concentration of the different white blood
cells

The adult human being has about 7000

white blood cells per microliter of blood (in comparison
with 5 million red blood cells).
Number of platelets in each microliter is about 300.000.
Origin of white blood cells
Genesis of white blood cells.
The different cells of the
myelocyte series are 1,
myeloblast; 2, promyelocyte;
3, megakaryocyte;
4, neutrophil myelocyte; 5,
young neutrophil
metamyelocyte; 6, “band”
neutrophil metamyelocyte;
7, polymorphonuclear
neutrophil; 8,
eosinophil myelocyte; 9,
eosinophil metamyelocyte;
10, polymorphonuclear
eosinophil; 11, basophil
myelocyte; 12,
polymorphonuclear
basophil; 13-16, stages of
monocyte formation
Origin of white blood cells
• Granulocytes and monocytes are formed in the bone marrow and
stored there on till they are needed
• Lymphocytes and plasma cells are produced in various hypogenous
tissues e.g. lymph glands, spleen, thymus, tonsils, Peyer's patches etc.
Life span of white blood cells
Granulocytes
• Circulation in the blood is 4- 8 hours
• In the tissues: 4 -5 days
• Life span of granulocytes in a few hours because they are destroyed in
action.
Monocytes
• Circulation in blood is about 10-20 hours
• In the tissues they become tissue macrophages and live for months
Lymphocytes
• Circulate between the blood and the lymphatic system. And can last for
weeks or months depending on the body’s need.
Neutrophils and macrophages
• Neutrophils and macrophages have similar line of
function and are the main phagocytic cells of the
immune system
• Macrophages are considered the first line of
defense when tissues are inflamed while
neutrophils are the second line of defense.
• White blood cells move by diapedesis which is
influenced by chemotactic response. Chemotaxis is
effective upto 100 micrometers away from an
inflamed tissue
• They both use ameboid movement to site of action
at velocities of 40 μm/min
Neutrophils and Macrophages
Phagocytosis is influenced by
• Natural structures (smooth surfaces vs rough surfaces)
• Presence or absence of protective protein coats
• Opsonization made possible by the complement cascade
• Neutrophils can phagocytize 1 -20 bacteria before they are
deactivated/destroyed
• Macrophages can phagocytize 100 bacteria, can also engulf whole red
blood cells, malaria parasites and digest them. they can then extrude
the residual products and survive and function for months
Eosinophils
• They are about 2% of the total white blood cell
• They are weak phagocytes
• They are produced in large numbers in people with parasitic infections
• Indicated parasites include: Schistosoma (schistosomiasis), trichinella
(Trichinosis)
• Action of eosinophil is possible by
1. Release of hydrolytic enzymes from their granules
2. Releasing highly reactive forms of oxygen lethal to parasites
3. Releasing a highly larvicidal polypeptide called major basic protein
Basophils and Mast cells
• Both of them release heparin (an anti coagulant)
• They release histamine, bradykinin and serotonin (mast cell mainly)
• They are indicated in the allergic reactions because of the propensity
of being attached to by Immunoglobin E (IgE) which causes allergic
reaction. When the matching antigen binds with the antibody IgE, it
causes the mast cell or basophil to rupture and release large
quantities of histamine, bradykinin, serotonin, heparin, slow-reacting
substance of anaphylaxis, and a number of lysosomal enzymes.
Monocytes
• Monocytes are precursor cells for the mononuclear phagocytic
system, which include cells such as macrophages, osteoclasts, and
microglial cells in connective tissue and organs
• They are myeloid cells, have large nuclei
• They function as antigen presenting cells.
White blood cells
Clinical conditions
• Leukopenia: bone marrow produces very few white blood cells
leaving the body unprotected
• Leukocytosis: This condition is where the leukocyte counts (primarily
neutrophils) are higher than normal.
• Leukemia: uncontrolled production of white blood cells caused by
cancerous mutation of a myelogenous or lymphogenous cell.
• Neutrophilia: with severe inflammation, the number of neutrophils in
the blood sometimes increases fourfold to fivefold—from a normal of
4000 to 5000 to 15,000 to 25,000 neutrophils per microliter.
Reticuloendothelial system (monocyte-
macrophage cell system)
The total combination of monocytes, mobile
macrophages, fixed tissue macrophages, and a few
specialized endothelial cells in the bone marrow, spleen,
and lymph nodes is called the reticuloendothelial system.
• Almost all cells of the system originated from monocytic
stem cells.
System exist as follows
• Tissue macrophages in the skin and subcutaneous
tissues (histiocytes): protects against invasion when the
skin is broken
• Macrophages in the lymph nodes. For pathogens that
move from blood to the lymph. Tissue macrophages on
the lymph nodes takes care of them
Reticuloendothelial system (monocyte-
macrophage cell system)
• Alveolar macrophages in the lungs: forms protective line of defense
for foreign particles that made come into the body through the lungs.
• If particles are digestible to digest and extrude residual out to join the
lymph. If they are not digestible, the macrophages form giant cell
capsules around the particles as seen in tuberculosis bacilli, silica dust
particle and carbon particles
• Macrophages (Kupffer cells) in the liver sinusoids: pathogens
through the GIT get stopped here as they pass into the portal blood
• Macrophages of the spleen and bone marrow: pathogens that enter
the general circulation meet another line of defense
Reticuloendothelial system (monocyte-
macrophage cell system)
platelets
• Platelets, also known as thrombocytes, are small, colorless, disc-shaped cell
fragments in our blood that play a vital role in blood clotting and maintaining
hemostasis.
• The platelets in the blood are replaced about once every 10 days; in other words,
about 30,000 platelets are formed each day for each microliter of blood.
Platelet functions
• Blood clotting: they are the first responders to the site of damage adhering
to exposed collagen in the damaged cells. Adherence leads to change in
shape and the release of clotting factors
• Vasoconstriction: they also contribute to the constriction of blood vessels
to minimize blood flow and reduce blood loss.
• Inflammation and wound healing: they play crucial roles here by releasing
growth factors and cytokines that attracts neutrophils and macrophages.
The factors also stimulates proliferation of fibroblast and endothelial cells
• Prevention of bleeding: adhering to the endothelium (inner lining)
• Antimicrobial activity: platelets contain antimicrobial peptides that can
neutralize bacteria, viruses, providing a defence mechanism
Clinical significance of platelets
• Hemostasis disorder: (hemophilia and von Willebrand disease)
• Thrombocytopenia: (low platelet count) can be caused by infections,
autoimmune disease or chemotherapy
• Thrombocytosis: (elevated platelet count)
• Platelets Transfusion: : In situations where a patient has a low platelet
count or requires emergency surgery, platelet transfusions may be
necessary to prevent excessive bleeding and maintain adequate
hemostasis.
COAGULATION/CLOTTING SYSTEM
The clotting system, also
known as the coagulation
cascade, is a series of reactions
involving various clotting
factors.
The process can be divided
into two pathways: the
intrinsic and extrinsic
pathways, which eventually
merge into a common pathway
COAGULATION/CLOTTING SYSTEM

• 1. Intrinsic Pathway: The intrinsic pathway is initiated when blood comes into
contact with collagen, a protein found in the damaged blood vessel wall. This
contact activates Factor XII, which then activates Factor XI, followed by Factor IX.
• 2. Extrinsic Pathway: The extrinsic pathway begins when tissue factor (TF) is
exposed from damaged cells. TF forms a complex with Factor VII, activating Factor
X.
• 3. Common Pathway: Both the intrinsic and extrinsic pathways lead to the
activation of Factor VIII and Factor V, which form a complex with Factor X. This
complex converts prothrombin (Factor II) into thrombin (Factor IIa). Thrombin
then catalyzes the conversion of fibrinogen (Factor I) into fibrin (Factor Ia). Fibrin
strands form a mesh that traps blood cells and platelets, creating a stable blood
clot enhanced by fibrin-stabilizing factor (factor XIII)
FIBRINOLYSIS
The fibrinolytic system is responsible for the dissolution of blood clots to
prevent excessive clotting and restore normal blood flow. It primarily involves
the interaction of plasminogen, tissue plasminogen activator (tPA), and
urokinase plasminogen activator (uPA).
the clotting and fibrinolytic
systems are tightly regulated
and work together to maintain
hemostasis. While the clotting
system forms a blood clot, the
fibrinolytic system ensures that
the clot is dissolved when no
longer needed.
1. Activation of Fibrinolysis:
Fibrin degradation products (FDPs) generated during clot dissolution inhibit the clotting system by
binding to Factor V and Factor VIII, impairing their function in the common pathway.
2. Negative Feedback Loop:
Plasmin generated during fibrinolysis can activate Factor V and Factor VIII, promoting clot dissolution.
Additionally, plasmin can activate protein C, which inactivates Factors V and VIII, further inhibiting clot
formation.
HEMOSTASIS
Hemostasis is a complex physiological process that enables the body to prevent
excessive blood loss following an injury or damage to blood vessels. It involves a
series of coordinated events that ultimately lead to the formation of a stable blood
clot, ensuring that blood loss is minimized and the healing process can begin. The
hemostatic mechanism can be divided into three main stages:
• vasoconstriction,
• platelet plug formation, and
• coagulation.
Immunity and immunodeficiency disease and
HIV
Immunity is defined as the capacity of the body to resist pathogenic
agents. It is the ability of body to resist the entry of different types of
foreign bodies like bacteria, virus, toxic substances, etc.
Immunity is of two types: Innate and Acquired immunity
Innate Immunity (natural or non specific immunity)
• First line of defense against any type of pathogens.
 INNATE IMMUNITY
Structures and mediators mechanisms

Gastrointestinal tract Enzymes in digestive juices and the acid in stomach destroy the toxic substances or organisms entering digestive tract through food.
Lysozyme present in saliva destroys bacteria.

Respiratory system Defensins and cathelicidins in epithelial cells of air passage are antimicrobial peptides.
Neutrophils, lymphocytes, macrophages and natural killer cells present in lungs act against bacteria and virus

Urinogenital system Acidity in urine and vaginal fluid destroy the bacteria

Skin The keratinized stratum corneum of epidermis protects the skin against toxic chemicals.
The β-defensins in skin are antimicrobial peptides.
Lysozyme secreted in skin destroys bacteria.

Phagocytic cells Neutrophils, monocytes and macrophages ingest and destroy the microorganisms and foreign bodies by phagocytosis.

Interferons Inhibit multiplication of viruses, parasites and cancer cells

Complement proteins Accelerate the destruction of microorganisms

ACQUIRED IMMUNITY
• Acquired immunity is the resistance developed in the body against
any specific foreign body like bacteria, viruses, toxins, vaccines or
transplanted tissues. So, this type of immunity is also known as
specific immunity
• Types of Acquired immunity
• Cellular immunity (T lymphocytes)
• Humoral immunity (B lymphocytes)
Lymphocytes are responsible for the development of these two types
of immunity.
ACQUIRED IMMUNITY
• Types of T Lymphocytes
1. Helper T cells or inducer T cells. These cells are also called CD4 cells
because of the presence of molecules called CD4 on their surface.
2. Cytotoxic T cells or killer T cells. These cells are also called CD8 cells
because of the presence of molecules called CD8 on their surface.
3. Suppressor T cells.
4. Memory T cells.
Types of B Lymphocytes
1. Plasma cells.
2. Memory cells.
Antigens: Antigens are the substances which induce specific immune
reactions in the body. (conjugated proteins like lipoproteins,
glycoproteins and nucleoproteins)
Antigens are of two types:
1. Autoantigens or self antigens present on the body’s own cells such as
‘A’ antigen and ‘B’ antigen in RBCs.
2. Foreign antigen s or non-self antigens that enter the body from
outside (Receptors and toxins of microbial organisms, materials from
transplanted organs or incompatible blood cells and allergens)
Based on response, non self antigens are of two types
1. Antigens that induce immunity (Immunogenicity)
2. Antigens that produce allergic reactions (allergic reactivity)
• Cell-mediated immunity is defined as the immunity developed by cell-
mediated response. It is also called cellular immunity or T cell immunity.
• Cell-mediated immunity does not involve antibodies.
• Usually, the invading microbial or non-microbial organisms carry the antigenic
materials.
• These antigenic materials are released from invading organisms and are
presented to the helper T cells by antigen-presenting cells.
Antigen-Presenting Cells
• Antigen-presenting cells are the special type of cells in the body, which induce
the release of antigenic materials from invading organisms and later present
these materials to the helper T cells.
• Types: macrophages, dendritic cells and B lymphocytes.
NB: B Lymphocytes function as both antigen presenting cells and antigen
receiving cells but their role as antigen presenting cells in not fully understood.
 Helper T cells activates all the other T cells
and B cells. It has a normal count varying
between 500 and 1500/mm3
• Helper cells are of two types: 1. helper-1
(TH1) cells and 2. helper-2 (TH2) cells
• Helper 1 iis concerned with cellular
immunity while helper 2 is concerned
with humoral immunity

Role of cytotoxic T cells: 1. binds with the antigens or organisms titghtly 2. enlarges and
relaeases cytotoxic cubstances like lysossmal enzymes 3. destroys invading organisms 4.
each cytotoxic can destroy a large number of microorganisms.
• Suppressor T cells: suppresses the activities of the cytotoxic and
helper T cells preventing them from destroying the body’s own tissue.
• Role of memory T cells: they are stationary in the lymphoid tissues.
When they are exposed to the same organism the second time, they
activate the other T cell for destruction of the invading organism
SPECIFICITY OF T-CELLS
• Each T cell is designed to be activated only by one type of antigen. It
is capable of developing immunity against that antigen only. This
property is called the specificity of T cells.
 HUMORAL IMMUNITY
• Humoral immunity is defined as the immunity mediated by antibodies, which are
secreted by B lymphocytes.
ACTIVATION OF B CELLS
• Recogniton of antigen by B cell by its b cell receptor
• Initiation of complex interaction b/w B cell receptor and antigen
• Macrophages (APC) release interleukin 1 for activation and proliferation of B cells
• Activated B cells proliferates
• Simultaneously, the antigen bound class II MHC molecules activates the helper T cells
Transformation of B cell
• Plasma cells: this produces antibodies (immunoglobulins)
• Memory cells: they produce copious number of antibodies on the second exposure
of the body to the same antigen at a faster rate.
 ANTIBODIES OR IMMUNOGLOBULINS
An antibody is defined as a protein that is produced by B lymphocytes in
response to the presence of an antigen.
Types of Antibodies and functions
1. IgA plays a role in localized defense mechanism in external secretions like tear
2. IgD is involved in recognition of the antigen by B lymphocytes
3. IgE is involved in allergic reactions
4. IgG is responsible for complement fixation
5. IgM is also responsible for complement fixation.
Mechanism of action
1. By direct action (agglutination, Precipitation, Neutralization and Lysis)
2. Through complement system (Classical pathway, Lectin pathway amd
alternate pathway)
Specificity of B
Lymphocytes
• Each B lymphocyte is
designed to be activated
only by one type of
antigen. It is also capable
of producing antibodies
against that antigen only.
This property of B
lymphocyte is called
specificity. In lymphoid
tissues, the lymphocytes,
which produce a specific
antibody, are together
called the clone of
lymphocytes.
• Natural killer cells: Natural killer (NK) cell is a large granular cell that plays an
important role in defense mechanism of the body.
Functions
• Destroy viruses
• Destroy viral infected or damaged cells which might form tumors
• Destroys malignant cells and prevent development of cancerous tumors
• Secretes cytokines such as interleukin-2, interferons, colony stimulating factor (GM-
CSF) and tumor necrosis factor-α
CYTOKINES
They are hormone-like small proteins acting as intracellular messengers (cell signaling
molecules) by binding to specific receptors of target cells.
Types: 1. interleukins 2. interferons 3. tumor necrosis factor 4. chemokines 5.
defensins 6. cathelicidins 7. platelet-activating factor
 IMMUNIZATION
Immunization is defined as the procedure by which the body is prepared to
fight against a specific disease. It is used to induce the immune resistance of
the body to a specific disease. Immunization is of two types:
1. Passive immunization (produced without challenging the immune system)
2. Active immunization (acquired by activating immune system of the body)
Both passive and active immunization can be Natural or artificial. Hence we
can have
• Passive natural immunization (prenatal and post natal transfer of IgG ans IgA)
• Passive artificial immunization (antiserum injection)
• Active natural immunization (clinical and subclinical infections)
• Active artificial immunization (Vaccines and Toxoids)
 IMMUNE DEFICIENCY DISEASE
Immune deficiency diseases are a group of diseases in which some components
of immune systems is missing or defective thereby making the body highly
susceptible to low virulence organisms which are called opportunists.
There are two types of immune deficiency diseases
1. Congenital immune deficiency diseases: they are inherited and occur due to
defects in B or T cells or both. E.g. DiGeorge syndrome (due to absence of
thymus) and severe combined immune deficiency (due to lymphopenia or
absence of lymphoid tissues)
2. Acquired immune deficiency diseases: occurs due to infection by some
organism. The most common is acquired immune deficiency syndrome (AIDS)
A person is diagnosed of AIDS when the CD4 count is below 200 cells per mm3
 HIV and AIDS
• The most common problem throughout the world
• Infection occurs when the glycoprotein from HIV binds to the surface receptors of T-lymphocytes, monocytes,
macrophages and dendritic cells to destroy them
• Causing slow progressive decrease in immune function and increasing the chances of opportunistic infection.
• Common opportunistic infections are pneumonia (Pneumocytosis carinii) and malignant skin cancer (Kaposi
sarcoma) these are also called AIDS-related diseases
• When HIV enters the body, it activates the enzyme reverse transcriptase to converts its viral RNA to viral DNA.
• The viral DNA then gets incorporated in the host cell DNA and this prevents normal activities. At the same time the
HIV increases in number inside the hosts body
• The infected cell ruptures and more HIV are released into the blood stream
• No symptoms develops for several week. This is known as the incubation period. Symptoms develops when
sufficient number of infected cells are ruptured.
• Common symptoms are: fatigue, loss of weight, chronic diarrhea, low grade fever, night sweats, oral ulcers, vaginal
ulcers e.t.c. this phase prolongs for about 3 years before the disease is diagnosed.
Mode of transmission
Infection spreads when secretions from the body of infected individual come in
contact with blood of the recipient through damaged skin or mucous membrane.
Most common ways are:
• Contaminated blood transfusion
• Contaminated needles or invasive instruments
• Transmission from mother to fetus during pregnancy
• Transmission from mother to child during delivery or breastfeeding and
• Vaginal sexual intercourse.
Prevention
• Public awareness on the seriousness and prevention
• Screen blood for HIV before transfusion/no sharing of needles
• Infected mothers can be treated with zidovudine to reduce infection on infants.
Infants should also be treated with zidovudine for 6 months
• Inform young adults and teenagers on safer sex techniques and use of condoms,
• Be faithful to your partner or better of, abstain from illicit sex.
• Deadline for submission of assignment remains 10am 19th march,
2025.