white blood cell

1. White Blood Cells (Leukocytes)
Blood Physiology
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2. White Blood Cells (Leukocytes)
Properties of WBC White blood cells
a. Nucleus: Have nucleus all the time.
b. Normal number: 4,800-10,000/mm3 of blood.
When infection occurs, WBC increase in number.
e.g. Neutrophils.
c. Defense: WBC’s fight infection by:
I. Direct destruction (e.g., Phagocytosis)
II. Producing : a. Antibodies &
b. Sensitized lymphocytes.
d. Mobility: Are highly mobile and reach tissue fluids.
f. Life span: Many (not all) live only a few days, may be
because of their engagement with pathogens except
memory cells, which provides life-long immunity .
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3. WBC TYPE
- Classification of WBC is depending on the appearance of their nuclei
and the presence or absence of granules in their cytoplasm.
1. WBCs are classified as either granular or agranular,
- Depending on whether they contain cytoplasmic granules (vesicles)
that are made visible by staining when viewed through a light
microscope.
Granular leukocytes include:-
- neutrophils, eosinophils, and basophils
Agranular leukocytes include:-
- lymphocytes and monocytes.
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5. 2. Depending on the appearance of their nuclei WBC is classified into
A. Polymorphonuclear (meaning “many-shaped nucleus”)
- Their nuclei are segmented into several lobes of varying shapes
- Neutrophils, eosinophils, and basophils are categorized as
polymorphonuclear.
B. Mononuclear (meaning “single nucleus”)
- Monocytes and lymphocytes are known as mononuclear.
- Both have a single, large, nonsegmented nucleus.
- Monocytes are the larger of the two and have an oval or kidney-
shaped nucleus.
- Lymphocytes, the smallest of the leukocytes, characteristically have a
large spherical nucleus that occupies most of the cell.
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Polymorphonuclear
Mononuclear

7. A. Neutrophils (primary phagocytic cells)
- Are the most numerous (~ 62%) , multinucleated (have 2-5 lobes)
- There granules is stained neutrally and showing no dye preference.
- These cells are the first defense in combating bacterial and fungal
infections.
- Neutrophils are attracted to the site of infection by cytokines that are
released by activated cells ~ endothelial, mast, and macrophage cells;
chemotaxis).
- They phagocytize “opsonized” microorganisms and digest the
particle within a phago-lysosome.
- Furthermore, they scavenge to clean up debris.
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9. B. Eosinophils (Normal Range: 2-3% of WBC
- There granulose stain red-orange with acidic dyes.
- Eosinophils primarily reside in the intestine and lungs and have limited
phagocytic capacity.
- Their primary role is in killing larger parasites that cannot be
phagocytized (e.g., enteric nematodes).
- They recognize the Fc portion of IgE antibodies bound to the parasite,
which triggers degranulation and release of compounds that are toxic to
both parasite and host tissues (peroxidases, nucleases, histamine, etc.).
- Their number increases in associated with allergic conditions (such as
asthma and hay fever) and with internal parasite infestations (for
example, worms).
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11. C. Basophils(Normal Range: < 1% of WBC)
- There granulose stained blue-purple with basic dyes
- They are involved in inflammatory and allergic responses.
- They are quite similar structurally and functionally to mast cells.
- When the specific antigen bind with immunoglobulin E (IgE), the
basophil and mast cell become activated and release large quantities
of histamine, heparin, and a number of lysosomal enzymes.
- These inflammatory mediators mediate the inflammatory response
(increased blood flow and permeability of the tissues).
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13. D. Monocytes / Macrophages (2-10%)
- They emerge from the bone marrow while still immature and circulate
for only a day or two before settling down in various tissues throughout
the body.
- When monocytes enter tissues where they undergo considerable
differentiation into macrophages that are characteristic for the tissue in
which they reside.
e.gs. - Interstitial macrophages in the GIT
- Alveolar macrophages in the lung,
- Kupffer cells in the liver,
- Osteoclasts in bone,
- Microglial cells in the brain
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14. Phagocytes
They are large immune cells that can engulf and digest foreign invaders
Three phagocytic cells:
Macrophages- are found in tissues throughout the body
Neutrophils- are cells that circulate in the blood but move into tissues
when they are needed
Dendiritic cells- migrate from blood to reside in tissues and are both
phagocytic and micropinocytic (ingest large amount of the surrounding
ECF)
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15. Phagocytosis
- Is a process where phagocytic cells ingest & destroy bacteria, cellular
debris, denatured proteins, and any toxins.
1. Phagocytosis by Neutrophils
- The neutrophils entering the tissues are already mature cells that can
immediately begin phagocytosis.
- A single neutrophil can usually phagocytize 3 to 20 bacteria before
the neutrophil itself becomes inactivated and dies.
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16. Phagocytosis by Macrophages
- Macrophages are the end stage product of monocytes that enter the
tissues from the blood.
- When activated by the immune system, they are much more powerful
phagocytes than neutrophils, often capable of phagocytizing as many as
100 bacteria.
- They also have the ability to engulf much larger particles, even whole
red blood cells or, occasionally, malarial parasites, whereas neutrophils
are not capable of phagocytizing particles much larger than bacteria.
- Also, after digesting particles, macrophages can extrude the residual
products and often survive and function for many more months.
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17. Mechanism of Phagocytosis
- Microbes adhere to the phagocyte
- Pseudopods engulf the particle (antigen) into a phagosome (a closed,
intracellular sac or vacuole formed by membrane invagination)
- Phagosomes fuse with a lysosome to form a phagolysosome
- Invaders in the phagolysosome are digested by proteolytic enzymes
- Indigestible and residual material is removed by exocytosis
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18. Mechanism of Phagocytosis
Macrophage- Presenting microbial antigens to lymphocytes
to initiate an adaptive immune response to the microbe.
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- Indigestible and residual material is removed by exocytosis

19. Mechanism of Phagocytosis
Macrophage- Presenting microbial antigens to lymphocytes
to initiate an adaptive immune response to the microbe.
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21. Criteria for Phagocytosis
Whether phagocytosis will occur depends especially on three selective
procedures.
1. Rough surface of pathogen
- Most natural structures in the tissues have smooth surfaces, which resist
phagocytosis.
- But if the surface is rough, the likelihood of phagocytosis is increased.
2. Having unprotected coat
- Most natural substances of the body have protective protein coats that
repel the phagocytes.
- Conversely, most dead tissues and foreign particles have no protective
coats, which makes them subject to phagocytosis.
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22. 3. Opsonization
- Is the process of coating pathogens to promote phagocytosis. The protein
which perform this function are called opsonin.
- There are two main opsonin:-
1. Complement C3b
2. Antibodies
C3b as Opsonin
- C3b is a complement protein which has ability to bind with microbial
surfaces.
- Phagocytes bear C3b receptors
- Once C3b protein coated microbes it will bind with C3b receptors in the
macrophage and trigger phagocytosis.
Antibody as Opsonin
- Antibodies specific to the pathogen are produced
- Antibodies bind to the surface of pathogen with its antigen binding site
- Phagocytes have receptor for the FC region of the antibody and
facilitate phagocytosis
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23. Blood Physiology
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24. C
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26. The Complement System
- The complement system is made up of about 25 proteins, mainly
produced by liver.
- From these complement protein the most important are:-
 C1-C9, Factor B, Factor D, properdin and mannose binding
lectin (MBL).
- Complement proteins circulate in the blood in an inactive form.
- The complement system can be activated by at least three separate
pathways.
Complement Activation Pathways
1. The Classical Pathway
2. The Alternative Pathway
3. The Mannan - Binding Lectin Pathway
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27. Complement has several functions :
1. Opsonization and phagocytosis.
- One of the products of the complement cascade, C3b protein coat
microbes and bind with C3b receptors in the macrophage and trigger
phagocytosis.
2. Lyses of cells ( e.g. bacteria and tumor cells).
- A combination of multiple complement factors designated as
C5b6789 form Membrane Attack Complex (MAC)
- This has a direct effect of rupturing the cell membranes of bacteria
or other invading organisms.
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28. 3. Chemotaxis.
- Fragment C5a initiates chemotaxis of neutrophils and macrophages,
thus causing large numbers of these phagocytes to migrate into the
tissue area adjacent to the antigenic agent.
4. Activation of mast cells and basophils
- Fragments C3a, C4a, and C5a activate mast cells and basophils,
causing them to release histamine, heparin, and several other
substances into the local fluids.
- These substances in turn cause increased local blood flow, increased
leakage of fluid and plasma protein into the tissue, and other local
tissue reactions that help inactivate or immobilize the antigenic agent.
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29. 1. The Classical Pathway
- The components of the Classic pathway are numbered from C1 to C9,
and the reaction sequence is C1- C4- C2- C3- C5- C6- C7- C8- C9.
- The classic pathway is initiated by an antigen-antibody reaction.
- When antibody bind with antigen it undergone conformational change
on the FC portion of the antibody (IgG and IgM) and this in turn
binds directly with the C1 molecule of the complement system.
NB.- IgA and IgE cannot activate complement
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30. The Classical Pathway cont’d
- C1 becomes activated when it binds to the ends of antibodies
- Once C1 is activated, it activates 2 other complement proteins, C2 and
C4 by cutting them in half (C2a and C2b, C4a and C4b)
- Both C2a and C4b bind together on the surface of the bacteria C2b
and C4a diffuse away.
- C2a and C4b bind together on the surface to form a C3 activation
complex.
- The function of the C3 activation complex is to activate C3 proteins.
This is done by cleaving C3 into C3a and C3b
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31. C3 Activation complex
- Many C3b molecules are produced by the C3 activation complex.
- The C3b bind to and coat the surface of the bacteria.
C3b is an opsonin
Opsonins are molecules that bind both to bacteria and phagocytes
Opsonization increases phagocytosis by 1,000 fold.
 C3a increases the inflammatory response by binding to mast cells
and causing them to release histamine
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32. Blood Physiology
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C2b and C4a diffuse away.

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Opsonins
C3a
C3b
C3b is an opsonin
Opsonins are molecules that bind both to bacteria and
phagocytes
Opsonization increases phagocytosis by 1,000 fold.
 C3a increases the inflammatory response
by binding to mast cells and causing them
to release histamine

34. Building the C5 activation complex
- When C3b binds to C2b and C4b it forms a new complex referred to
as the C5 activation complex
- The C5 activation complex (C2a, C4b, C3b) activates C5 proteins by
cleaving them into C5a and C5b
C5a disperses away from the bacteria.
- Binds to mast cells and increases inflammation.
- Most powerful chemotactic factor known for leukocytes
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35. Building the Membrane Attack complex
- C5b on the surface of bacteria binds to C6
- The binding of C6 to C5b activates C6 so that it can bind to C7
- C7 binds to C8 which in turn binds to many C9’s
- Together these proteins form a circular complex called the membrane
attack complex (MAC)
The Membrane Attack complex causes Cytolysis.
- The circular membrane attack complex acts as a channel in which
cytoplasm can rush out of and water rushes in.
The cells inner integrity is compromised and it dies
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36. Blood Physiology
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Membrane Attack complex
C5a

37. Overview
Membrane
Attack complex

38. Blood Physiology
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39. Lymphocytes
- Lymphocytes are a type of white blood cell derived originally in the
embryo from pluripotent hematopoietic stem cells in the bone
marrow.
- Defend the body against cancerous cells, pathogens, and foreign
matter.
- Lymphocytes fall into three classes: B lymphocytes, T lymphocytes
and natural killer (NK) cells.
- In circulating blood, about 80% of the lymphocytes are T cells, 15%
B cells, and 5% NK and stem cells.
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40. B- Lymphocytes (B cells)
- B cells develop from multipotent hematopoietic stem cell in the bone
marrow in adults.
- The immature B-cells remain in the bone marrow to complete
maturation.
- Once they are fully developed, B cells are released into the blood
where they travel to lymphatic organs.
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41. T - Lymphocytes (T cells)
- During fetal development, the bone marrow releases undifferentiated
stem cells into the blood. Some of these colonize the thymus and
become T cells.
- Migrated T-cells to thymus are further differentiated or
“preprocessed”.
- Here, T-cells proliferate and diversify and learn to recognize their self
antigens, so that they do not destroy their own tissues
- In the thymus, dangerous T-cells that attack self tissues are
destroyed & phagocytized (thymic selection).
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43. Types of T- lymphocytic cells
- There are three major classes of T cells that play specific roles in the
destruction of antigens.
1. Killer (Cytotoxic) T-cells:
- T cells attack viruses, fungi, transplanted cells and cancer cells
- are responsible for transfusion reactions and the rejection of
transplanted organs.
- Kill pathogens directly by binding to them and lysing or causing them to
burst open.
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44. 2. Helper T- cells:
- Are the most numerous than others.
- Immature T helper cells (TH0), differentiate into TH1 and TH2 cells.
- TH1 cells promote the activation of cytotoxic T cells while TH2 cells
are required for B-cell activation.
Interaction TH1 – macrophages
Interaction TH2 - B lymphocytes
- The AIDS virus selectively invades helper T cells, destroying or
incapacitating the cells that normally orchestrate much of the
immune response. A rapid decline in the number of CD4+ T cells.
- They produce lymphokines that produce different chemicals called
interleukins (interleukin 2- to - 6).
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45. 3. Suppresser T cell
- As the pathogen is defeated and disappears from the tissues,
suppressor T cells release interleukins that inhibit T and B cell
activity.
- This slows down the immune reaction and keeps it from running out
of control.
- Suppressor T cells may help to prevent autoimmune diseases.
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46. T helper cell activation
1. Step 1:- An antigen presenting cell (APC) dendritic cells or
macrophages), internalizes and processes an antigen to display on its
surface using an MHC class II molecules.
2. Step 2:- the APC presents the processed antigen with MHC class II to a
Naive T helper cell (TH) cells.
- Processed antigen bind to TCR of helper T cell and MHC-II bind to
CD4 glycoprotein on the surface of T-helper cells(signal-1).
- Apart from the TCR signaling a strong match, the T cell-expressed
protein CD28 signals to recognize the CD80 (B7) on the APC
(signal-2). This will activate TH cells.
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47. 3. Step 3:- upon dual recognition (first signal MHCII: CD4 ; antigen with
TCR) and (second signal ;CD80 with CD28) the naïve TH cell is
activated.
- In addition to dual recognition the APC provides co-stimulation to TH
cells via CD40, which becomes activated on TH cells via CD40 ligand
(CD40L) expressed on TH cells.
- This enable the APC to release interleukins-1 for further TH cell
stimulation.
4. Step 4:- The T- helper cell in turn release interleukin-2 (IL-2) to the
surface, again IL2 bind to TH and causes TH cell to undergoes
differentiation into a memory cells or into effector cells.
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49. T helper cell activation
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50. T helper cell activation
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Cytotoxic T cells
B cells
TH1 cell release IL-2, IL-12, IFN-γ and
(TNF-a) to stimulate cytotoxic T cells
TH2 cells secret IL-2 ,IL-4 and IL-5 for B cell differentiation

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- The TH1 cells tend to form when
- there is lots of strong
stimulation by the
phagocytized antigen
- The phagocytized antigen
secret IL-12 to stimulate the
helper cell into TH1 cell
- The sources of infection is
viral
- Secret (IL-2, IL-12, IFN-γ
and TNF-alpha to activate
cytotoxic T cells
- The TH2 cells tend to form
when
- There is weaker, more
prolonged stimulation by the
phagocytized antigen .
- The phagocytized antigen
secret IL-4 to stimulate the
helper cell
- The sources of infection is
bacterial
- secret IL-2 ,IL-4 and IL-5 for
B cell proliferation and
differentiation

52. N.B.
- Helper T cells develop/ differentiate into TH1 and TH2 cells depending on
the cytokine environment in which they are activated and the sources of
infection.
- The TH1 cells tend to form when
- there is lots of strong stimulation by the phagocytized antigen and lots
of activation of the innate immune system.
- the phagocytized antigen secret IL-12 to stimulate the helper cell
- The sources of infection is viral
- Secret (IL-2, IL-12, interferon-gamma (IFN-γ) and tumor-necrosis
factor-alpha (TNF-a) to activate cytotoxic T cells and NK cells
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53. N.B.
- The TH2, by contrast, tend to form with weaker, more prolonged
stimulation with less activation of innate mechanisms.
- the phagocytized antigen secret IL-4 to stimulate the helper cell
- The sources of infection is bacterial
- TH2 cells secret IL-2 ,IL-4 and IL-5 for B cell proliferation and
differentiation.
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54. B Cell Activation
- Inactivated B cells circulate in the blood until they come in contact
with an antigen and become activated.
- On the surface of a B-cell there is a B cell receptor (BCR) protein.
- The BCR enables B cells to capture and bind to exogenous antigens
antigen such as Bactria or parasite.
- Once bound, the antigen is internalized and digested by the B cell and
certain molecules from the antigen are attached to another protein
called a class II MHC protein.
- This antigen-class II MHC protein complex is then presented on the
surface of the B cell.
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55. - Helper T(TH2) cell comes in contact with the antigen-class II MHC protein
complex in the B cell's surface.
- Processed antigen bind to TCR of helper T cell and MHC-II bind to CD4
glycoprotein on the surface of TH2 cells. (signal-1).
- In addition, the TH2 cell uses its CD28 to recognize the CD80 (B7) on the B
cells (signal-2). This will activate TH2 cells.
- upon dual recognition (first signal MHC: CD4 ; antigen with TCR) and
(second signal ;CD80 with CD28) the naïve TH2 cell is activated.
- In addition to dual recognition the B cell provides co-stimulation to TH2
cells via CD40, which becomes activated on TH2 cells via CD40 ligand
(CD40L) expressed on TH2 cells.
- This enable the APC to release interleukins-1 for further TH cell
stimulation.
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56. - Once APC/B-cell deliver antigen to the TH2-cell successfully it release
interleukins-1 for further stimulation.
- The TH2 in turn release interleukin-2 (IL-2) to the surface, again IL2
bind to TH2 and causes TH2 cell to release b lymphocyte growth factor
called IL- 4, IL- 5, and IL- 6.
- These factor causes mitotic differentiation of b cells into memory cells
and plasma cells.
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57. C
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58. Blood Physiology
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ActivatedTH2 cell
IL1
- The TH2 in turn release
interleukin-2 (IL-2) to the
surface, again IL2 bind to
TH2 and causes TH2 cell to
release b lymphocyte growth
factor called IL- 4, IL- 5, and
IL- 6.
- These factor causes mitotic
differentiation of b cells into
memory cells and plasma
cells

59. B CELL activation
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60. B CELL activation
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61. Plasma B cells
- Plasma B cells create antibodies that are specific to a specific
antigen.
- The antibodies circulate in bodily fluids and blood serum until they
bind to an antigen.
- Antibodies debilitate/weaken antigens until other immune cells can
destroy them.
- It can take up to two weeks before plasma cells can generate enough
antibodies to counteract a specific antigen.
- Once the infection is under control, antibody production decreases.
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62. Memory cells B-cell
- Some activated B cells form memory cells.
- Memory B cells enable the immune system to recognize antigens
that the body has previously encountered.
- If the same type of antigen enters the body again, memory B cells
direct a secondary immune response in which antibodies are
produced more quickly and for a longer period of time.
- Memory cells are stored in the lymph nodes and spleen and can
remain in the body for the life of an individual.
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63. Structure of antibodies
- There are 2-heavy and 2-light chains, which have constant and
variable portions (see figure).
Constant portion = provides an attachment surface on tissues
Variable = is a place where antigens attach to antibodies specifically
- Antibodies produced by plasma cells join gamma globulins through
the blood, thus, their name immunoglobulin (Ig).
- There are 5-types of immunoglobulin : IgA, IgD, IgE, IgM, IgG
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64. Structure of antibody
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65. Mechanism of action of antibodies
1. Neutralization: The antibodies cover the active sites of the invader
and inactivate the toxic sites of the antigens that it uses to infect
its host cell.
2. Oposinization:- Coating of bacteria with antibody to enhance
phagocytosis.
3. Precipitation:- In precipitation, the cross-linking of soluble
antigen molecules - molecules dissolved in body fluids.
- The insoluble antigen-antibody complex forms immobile
precipitates and are disposed of by phagocytosis.
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66. Mechanism of action of antibodies cont’d
4. Agglutination: involves the clumping or binding of bacterial
antigens to each other, so that they become dysfunctional.
- Agglutination is possible because each antibody molecule has at
least two antigen-binding sites.
- IgM can link together five or more viruses or bacteria.
- These large complexes are readily phagocytosed by macrophages.
5. Complement activation :- Antibody bonding triggers classical
pathway
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67. C
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69. Cytotoxic T cell activation
- When a foreign particle, such as a virus, infects the body, it is taken
up by macrophages (or dendritic cells) via phagocytosis.
- Within the macrophage, the partially digested virus particles provide
foreign antigens that are moved to the surface of the cell membrane.
- At the membrane, these foreign antigens form a complex with the
MHC-II molecules.
- This combination of MHC-II molecules and foreign antigens is
required for interaction with the receptors on the surface of helper T
cells (TH1).
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70. Cytotoxic T cell activation cont’d
- Processed antigen bind to TCR of helper T cell (TH1) and MHC-II
bind to CD4 glycoprotein on the surface of TH2 cells.
- Once APC deliver antigen to the TH1-cell successfully, the
macrophage is stimulated to secrete the cytokine known as
interleukin-1.
- Interleukin-1 activate TH1 cells. The activated TH1 cells, in turn,
secrete interleukin-2(IL-2), IL-12, (IFN-γ) and TNF-a.
- These factor causes the TH1 cells to undergo proliferation into
- T memory cells- which will be distributed to immune tissues for
future protection
- Killer cytotoxic T cells that will interact with infected cells to
destroy them
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71. Cytotoxic T cell activation cont’d
- The infected cell will present pieces of the antigen on its surface using a
MHC- I molecule, acting as an APC.
- Processed antigen bind to TCR of cytotoxic T cell and class I MHC
molecules interact with the cytotoxic T cell’s CD8 co-receptor.
- When a TC cell recognizes a complex of antigen and MHC-I protein on
a diseased or foreign cell, it releases cytotoxic chemicals that will
destroy it.
NB:-
- Because cytotoxic T cells do not bind to MHC self-antigens in the
absence of foreign antigens, normal body cells are protected from lethal
immune attack.
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72. Among these cytotoxic T cell chemicals are:-
(1) Perforin, which creates holes in its plasma membrane and destroys the
cell in the same manner as the perforin released by natural killer cells
(2) Lymphotoxin, which destroys the target cell’s DNA; and
(3) Tumor necrosis factor (TNF), which kills cancer cells by unknown
mechanisms.
(4) Interferone - TC cells also secrete interferon, which inhibits the
replication of viruses, and
(5) Interleukins - attract neutrophils and natural killer cells; attract
macrophages, stimulate their phagocytic activity, and inhibit them from
leaving the area
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interleukin-2(IL-2), IL-
12, (IFN-γ) and TNF-a
THC1

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To kill the infected cells cytotoxic T cell secret
chemicals such as:-
Perforin to creates holes in its plasma membrane
Lymphotoxin to destroys the target cell’s DNA
Interferone - to inhibits the replication of viruses
Interleukins – to attract neutrophils and natural
killer cells
Tumor necrosis factor (TNF) to kills cancer cells

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76. Natural killer (NK) cells
- Comprise 5-10% of the peripheral lymphocytes
- Lack BCRs and TCRs (Null cells)
- Lack immunological specificity and memory
- They destroy virus-infected host cells and cancer cells.
- Receptors on the surface of the natural killer cell interact with
proteins on the captured cell.
- If a cell triggers more of the NK cell's activator receptors, the killing
mechanism will be turned on.
- If the cell triggers more inhibitor receptors, the NK cell will identify
it as normal and leave the cell alone.
Blood Physiology
Don. Siyum A. 92
WBC

77. - When NK cell recognizes an abnormal cell, it secretes proteins called
perforins, which bind to the enemy cell surface and make holes in its
membrane. This ultimately causes the target cell to burst.
- Natural killer cells recognize and destroyed host cells with no MHC
class I surface molecules
Blood Physiology
Don. Siyum A. 93
WBC
NK cell
Enemy
cell
Perforins
Rupture of plasma membrane

78. Blood Physiology
Don. Siyum A. 94
WBC
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