White Blood Cells

1. White blood cells
Prof. Dr Saba Khalid
MBBS, M-Phil, Ph-D

2. A. Granulocytes
1. nucleus: >1 lobe
2. granules
3. life span: few days
4. neutrophils,
eosinophils, basophils

3. V. Leukocytes
B. Agranulocytes
1. nucleus: round or
horseshoe shape
2. no specific granules
3. lymphocytes &
monocytes

4. Leukocytes
Neutrophils (12.5,12.6)
1. 60-70% of
leukocytes
2. 12-15 mm diameter
3. nucleus: 2-5 lobes

5. WHITE BLOOD CELLS
• Leukocytes or WBCs are the mobile units
of the body’s immune defense system.
• Immunity is the body’s ability to resist or
eliminate potentially harmful foreign
materials or abnormal cells.
• WBC count: 5000 to 11000/ul of blood

6. • Leukocytosis:
• occurs in:
• a) Infections
• b) Allergy
• c) Common cold
• d) Tuberculosis
• e) Glandular fever

7. White Blood Cells
• Classified as Granulocytes and Agranulocytes.
• Life of granulocytes:
• 4 to 8 hours in the blood
• 4 to 5 days in tissues
• Monocytes also have a short transit time:
• 10 to 20 hours in the blood.
• In tissue they swell to much larger size to become tissue macrophages.
• Lymphocytes have a life spans of weeks or months.
• Platelets are replaced about once every 10 days, about 30,000 platelets
are formed each day/ul of blood.

8. • Granulocytes:
• All are nucleated.
• 1) Neutrophils (microphage): 60- 70%
• 2) Eosinophil: 2.3%
• 3) Basophil: 0.4%
• 4) Monocytes: 5.3%
• 5) Lymphocytes: 30%

9. Formation of Leucocytes
• In the embryo:
• WBCs develop in the mesoderm and migrate into the blood vessels.
• At the 3rd month of intrauterine life:
• Lymphopoiesis first appears in the liver and thymus.
• In last trimester:
• Bone marrow forms stem cells. Some of which migrate to the thymus where T
lymphocytes take origin.
• At birth, the thymus weighs 10 to 12 g and cell mediated immunity well developed so
that graft rejection can occur.
• In the extrauterine life the granulocytes exclusively develop in the red bone
marrow.
• Lymphocytes and monocytes, also develop from stem cells in the bone
marrow.

10. Granulopoiesis
• Haemocytoblast
• ↓
• Myeloblasts (18um), large nucleus, several nucleoli
• ↓
• Promyelocyte (have reniform nuclei, multiple nucleoli, a few granules)
• ↓
• Myelocytes (3 types: neutrophilic, eosinophilic and basophilic) depending upon the
staining characters of their granules. Cytoplasm is more extensive, and nuclei are
smaller and there are no nucleoli.
• The cells are in the bone marrow.
• ↓
• Metamyelocytes
• ↓
• Neutrophils, eosinophils and basophils
• The complete maturation process from myeloblasts to neutrophils takes about 3
days.

11. Development

13. • The signs of maturation:
• A) Cell and nucleus size becomes smaller
• B) Cytoplasm becomes less basophilic except in
plasma cell
• C) Granules appear with characteristic staining
characters.

14. Neutrophils
• Size: 10-14 µ. The neutrophils show amoeboid movements and
these cells do not divide.
• Cytoplasm contain granules. Neurophils are rich in lysosomal
enzymes.
• Neutrophils have a short stay in the circulation; after migration to the
tissue, they never return to the blood stream. Survival time is 9 days.
• Stained by acidic and basic dyes.
• Nucleus is multilobed, number of lobes varies b/w 1-5.
• Aged cells have more lobes.
• 50-70% of all leucocytes

16. Leukocytes
4. specific granules
a. alkaline
phosphatase
b. collagenase
c. lactoferrin
d. lysozyme
e. antibacterial basic
proteins

17. 5. azurophilic granules
a. lysosomes
6. life span 1-4 days in
Connective tissue.
7. function
a. defense against
bacterial infection
b. diapedesis,
phagocytosis

18. • Neutrophils are called microphages.
• Counting the number of lobes and grouping them is called Arneth
count.
• Shift to left means (increase no of young and predominant WBCs).
• Shift to right means, old cells are predominant.
• During acute infection there is shift to left.
• Recovery Phase:
• Shift to right.
• Their reaction ranges from mild allergy → anaphylactic shock.

19. • Neutrophilia:
• Increase in Neutrophil count.
• Occurs in:
• 1) Acute bacterial infections maintains increased neutrophil production in
the bone marrow.
• 2) metabolic disorders
• 3) injections of foreign proteins
• 4) poisoning by chemicals and drugs like lead,
• mercury
• 5) poisoning by insect venom
• 6) after acute hemorrhage
• 7) ACTH of the anterior pituitary glands and cortisol of the adrenal cortex
• 8) adrenaline and exercise

21. Development
• Originate from pleuripotent stem cells and become Comitted stem
cells (for ganulocyte & monocyte) CFUGM
• ↓
• Myeloblast (large cell with nucleus)
• ↓
• Promyelocyte
• ↓
• Myelocyte (megamyelocyte)
• ↓
• Metamyelocyte
• ↓
• juvenile or band stage
• ↓
• Mature

23. Properties of Neutrophils
• 1) Amoeboid movement:
• Remain in circulation for 4-8hrs & then passed
to the tissues, they show amoeboid movement.
• 2) Margination and diapedesis:
• They show margination & diapedesis, lined up
along capillary wall (margination).
• 3) Squeeze through pores b/w adjacent
endothelial cells.

24. • 4) They show chemotaxis (move towards the source of chemotactic
factors).
• Chemotactic factors include bacterial toxins & degenerative products
from inflammed tissues.
• C5a is very important chemotatic factor.
• They reach at the site of infection & phagocytose the organisms.
• It can phagocytoze 3 to 20 bacteria.
• After that they die and called pus cells.
Granules contain myeloperoxidase, defensin, elastases.
• Pyrogens: are released by neutrophils and cause fever.

25. Causes of Phagocytosis
• Abnormal rough surface.
• Abnormal charge on the surface of organism.
• Opsonization:
• When microorganism enter the body, immune system produce antibodies
called opsonins like IgG. It coats the surface of bacteria, so that they
become tasty to be engulfed.
• Before ingestion, certain bactericidal substances are produced by
neutrophils i.e; myeloperoxidase and these first kill bacteria to make their
ingestion easy i.e; superoxide, hydro-oxyl ions, hydrogen peroxide &
hydrochlorate (HOCL3).
• Respiratory burst is by enzyme- NADPH oxide, Superoxide Dismutase,
Catalase.

26. Eosinophils
• Normal Size:10-14 µ size
• Constitute about 2%.
• Nucleus is bi-lobed giving appearance of spectacle.
• In cytoplasm:
• Acidophilic granules are present.
• Are weak phagocytes.

27. Eosinophils
1. 2-4% of leukocytes
2. 12-15 mm diameter
3. bilobed nucleus
4. ~200 eosinophilic
granules

28. • They have high peroxidase content which
accounts for their parasiticidal action.
• Collects around site of allergic reactions and are
increased in infestation of the body by parasites
and in skin diseases.
• They release Major basic protein (MBP) which
have bactericidal action.

29. Eosinophils
• They help to detoxify the products of allergic reaction by
removing histamine, bradykinin & serotonin.
• They release hydrolytic enzymes from their granules,
which are modified lysosomes.
• They release highly reactive form of oxygen that are
lethal to paracites.
• They kill by releasing larvacidal polypeptide called major
basic protein.

30. Eosinophils
4. ~200 eosinophilic
granules (12.5,12.8)
5. antiparasitic &
modulate inflammation
Note: staining of rbc’s
indicates acid stain color,
which may vary considerably.
Giemsa stain.

31. • Engulf antigen-Antibody (Ab) complexes, when they have initiated
the immune response.
• Migrate to the areas of inflammation during resolution and remove
tissue debris. So help in tissue resolution.
• Contain Pro-fibrinolysin activated to fibrinolysin, which dissolute the
blood clots.
• Eosinophils migrate into blood clots & help dissolving them.
• Eosinopenia is produced by cortisol and ACTH as happens under
stressful conditions.

32. • Eosinophilia: means increase in eosinophil
count.
• This occurs in:
• 1) allergic conditions
• 2) Asthma
• 3) Blood parasitism (malaria, filaria)
• 4) Intestinal parasitism
• 5) Scarlet fever

33. Basophils
• Are the smallest of the WBCs.
• Percentage in blood is (0.4-1.1%).
• Normal Size: 10 µ.
• Large nucleus present.
• Darkely stained granules in cytoplasm, which are so darkely stained that
they even masked nucleus (basophilic stain).
• Granules contain histamine, bradykinin, Heparin (natural anticoagulant),
serotonin.
• In the tissues, large cells are present called mast cells, which are
functionally related to basophils.

34. Basophils
• On the membranes of basophils and mast cells, receptor
for IgE antibodies are present.
• When the antigen to which person is sensitive enters the
body Ag-Ab reaction happens on the surface of Mast
cells and Basophils and cause rupture of these cells.
• Histamine and other substances are released and
allergic reaction is produced.
•
• Heparin is released.

35. Basophils
1. < 1% of leukocytes
2. 12-15 mm diam.
3. 0.5 mm
diam.basophilic granules

36. • Mast Cells:
Mast cell is a large tissue cell resembling the basophil.
• It is present in bone marrow and around the cutaneous
blood vessels but does not enter the blood circulation.
• The mast cell plays an important role in producing the
hypersensitivity reactions like allergy and anaphylaxis.
• It secretes histamine, serotonin and hydrolytic enzymes.

37. • Basophilia occurs in:
• 1) Small pox
• 2) Chicken pox
• 3) polycythemia vera

38. • Leucopenia:
• The decrease in the total white blood cell count occurs in
the following pathological conditions:
• 1. Anaphylactic shock
• 2. Cirrhosis of liver
• 3. Disorders of spleen
• 4. Pernicious anemia
• 5. Typhoid and paratyphoid fever
• 6. Viral infections

39. • Leucocytosis:
• Occurs in the common pathological conditions
like:
• 1. infections
• 2. Allergy
• 3. Common cold
• 4. Tuberculosis
• 5. Glandular fever

41. Monocyte
• Largest WBCs, size: 16-18 µm.
• Have single kidney shaped indented nucleus at
periphery.
• Cytoplasm is without visible granules.
• Remain in circulation for 72 hrs, then migrate into tissue,
where enlarge to form tissue macrophages.
• Life span: 72 hrs in circulation, 3 months in tissues.
• Macrophages can be mobile or fixed.

42. Monocytes
1. 12-20 mm diameter
2. nucleus: oval,
horseshoe/kidney
shaped, eccentric
3. become wandering
macrophages after
diapedesis

43. Monocytes
• Fixed phagocytic cells:
• Present in the different parts of reticuloendothelial cells
i.e; Kuffer cells in liver, in alveoli→ alveolar
macrophages.
• In Bone marrow & lymph nodes & in pulp of spleen and
in skin histiocytes.
• All of these are derived from monocytes.
• Osteoclasts also develop from monocyte series and
causes bone resorption.

44. • Formation of monocytes:
• monocytes are also developed from bone
marrow.
• The stem cell is colony forming unit-
Granulocyte-Monocytes (CFU-GM) that
develops into myeloblast.
• The myeloblast is converted into monoblast,
which develops into monocyte.

45. • Monocytosis occurs in:
• 1) Tuberculosis
• 2) Syphilis
• 3) Malaria
• 4) Kala azar
• 5) Glandular fever

46. Functions
• Phagocytic activity is shown in tissues only but not much
in blood.
• Macrophage can phagocytize upto 100 bacteria, also
engulf dead neutrophil. Macrophage can ingest old
RBCs and large organisms.
• Monocytes show margination, diapedesis and
chemotaxis.
• When these engulf bacteria, it is broken, antigen is
isolated, processed and then presented to immune
system to initiate the immune reaction.

48. Lymphocytes (Agranulocytes)
• Depending upon size, they are large or small.
• Percentage in blood: 25-40%.
• There are two types according to function.
• 1) T lymphocytes: Thymus dependent
• 2) B lymphocytes: bursa dependent.

49. Formation of Lymphocytes
• The formation of lymphocytes are in the bone
marrow.
• The PSC gives origin to colony forming units
(CFU) and lymphoid stem cells (LSC).
• The lymphoid stem cells give origin to
lymphoblasts, which develop into lymphocytes.
• These lymphocytes are released from the bone
marrow into the circulation.

50. • Some of the lymphocytes enter the thymus.
• In thymus, these lymphocytes are processed
and come out of thymus as T lymphocytes.
• The remaining cells enter liver and bone marrow
and are processed as B lymphocytes.

51. • In human beings, bone marrow or liver correspond to
bursa of fabricus.
• During fetal life, T and B lymphocytes originate from
common stem cells.
• T lymphocytes:
T cells migrate from bone marrow to thymus where it
proliferate to form T lymphocyte
• Processing occur in fetal life and some period after birth.

52. • Lymphocytosis occurs in:
• 1) Infectious hepatitis
• 2) Mumps
• 3) Malnutrition
• 4) Rickets
• 5) Syphilis
• 6) Thyrotoxicosis
• 7) Tuberculosis

53. • Leukemia:
• It is associated with abnormal and uncontrolled increase
in total white blood cell count It is a cancer of blood. The
abnormal of leucocytes is reduced on X-rays exposure
and treatment with antileukaemic drugs.
• Agranulocytosis:
• There is marked reduction in the number of granulocytes
and these persons are highly susceptible to bacterial
infections.

54. B Lymphocytes
• Other cells migrate to fetal bone marrow or fetal liver, processed and form B
lymphocytes.
• Then migrate to lymphoid tissue and proliferate to form more and more B
lymphocytes.
• T lymphocytes:
• Are involved in cell mediated immunity and tissue graft reaction.
• B lymphocytes:
• Are involved in humoral immunity.
• Types of T lymphocytes:
• 1) Cytotoxic or killer
• 2) Helper
• 3) Suppressor or regulatory
• 4) Memory T cells

55. Helper cells
• Produce lymphokines or cytokines CD4, which
regulate many aspects of immune system.
• 1) helps macrophage in antigen processing.
• 2) regulate function of B-lymphocytes
• 3) regulate killer cells
• 4) regulate suppressor cells
• All the above functions are performed with the help of
cytokines.
• They are damaged by AIDS virus results in AIDS.

56. Cytotoxic and Suppressor cells
• Cytotoxic cells:
• kill bacteria or organism by CD8.
• By producing a protein perforin, it
produces perforation in bacterial cells.
• Suppressor cells:
• Regulate the function of helper and killer T
cells. These help in immune tolerance for
bodies own cells.

57. B Lymphocytes
• Are involved in humoral immunity.
• When antigen activates the B lymphocytes, there is formation of
Plasma blast→ Plasma cells, which have got highly developed
endoplasmic reticulum.
• Five types of Immunoglobulins:
• IgA, IgE, IgM, IgD, IgG (IgM is formed first on the exposure of
antigen and than IgG are formed)
• 75% is IgG.
• Antibodies act on antigens directly or indirectly.

58. • Direct action:
• A) Include precipitation
• B) Agglutination
• C) Neutrilization
• D) Lysis

59. • Indirect action:
• Is through activation of complement system
• Inactive proteins present in body fluid, activated
in a cascade manner.
• C4a, 3a, 5a activate mast cells and basophils.
• C3b causes opsonization.
• C5a is powerful chemotatic agent.

60. • C5b6789 cause lyses of cells.
• Antibodies are immunoglobulin (Ig), molecular wt. is variable.
• Each Immunoglobulin (Ig) has a polypeptide chain (2 heavy + 2 light
chains).
• They have constant and variable portion.
• Constant is same in all Igs, but variable is different and specific for
different antibodies and have sites for antigen binding.
• When B Lymphocytes are exposed to antigens, memory B cells are
formed.