Variations in the count of white blood cells

Increase in leukocyte count is known as leukocytosis. Decrease in leukocyte count is known as leukopenia. The term leukopenia is generally used for pathological conditions only.

PHYSIOLOGICAL VARIATIONS – physiological leucocytosis

1. Age: In infants, the white blood cell count is about 20,000 per cu mm and in children, it is about 10,000 to 15,000 per cu mm of blood.

2. Sex: The white blood cell count is slightly more in males. In females, the leukocytes count is increased during menstruation, pregnancy and parturition.

3. Diurnal variation: The cell count is minimum in early morning and maximum in the evening

4. Exercise: The white blood cell count is increased slightly during exercise.

5. Sleep: During sleep, the white blood cell count is minimal.

6. Emotional conditions: During emotional conditions like anxiety, the count is increased.

7. Pregnancy: During pregnancy, the leukocyte count is increased.

8. Food taking: especially after proteinic food taking that is explained by its antigenic character.

9. Ovulation: insignificant leucocytosis (neutrophyly) at simultaneous eosinophils amount lowering.

10. Fits: up to 20000 and more independently on reasons.

11. Sharp changing of environmental temperature

PATHOLOGICAL VARIATIONS

All types of leukocytes do not share equally in the increase or decrease in the total leukocyte count. In general, the neutrophils and lymphocytes vary in opposite directions.

Leukopenia

The decrease in the total white blood cell count occurs in the following pathological conditions:

1. Anaphylactic shock

2. Cirrhosis of liver, viral hepatitis in acute phase

3. Disorders of spleen

4. Pernicious anemia

5. Typhoid and paratyphoid and

6. Viral infections: measles, rubeole, influenza

7. Chemicals action (benzol)

8. After irradiation

9. Hypoplastic and aplastic processes

10.Medicines (amidopyrinum, butadionum, rheopyrinum, sulphanilamides, cytostatics)

10. Endocrine diseases (acromegaly, thyroid pathology)

11. Leucoses (cytostatics overdosage)

12. New-formations metastazing in bone marrow

Lymphocytopeny

1. Primary immune pathology (different-typed agammaglobulinemy, tymome)

2. Blood system pathology (aplastic anemias, leucosis)

3. Kushing's syndrome

4. Kidney insufficiency

5. AIDS – specific symptom

6. Irradiation

7. Corticosteroid therapy and alkylic drugs taking

8. Hard edemas

9. Systemic red lupus

10. Purulent inflammation

11. Tuberculosis

Neutropeny

1. Viral infections

2. Chronic infections

3. After cytostatics taking

4. Irradiation

5. Aplastic and vitamin B12-deficient anemias

6. Agranulocytosis

Leukocytosis

Leukocytosis occurs in the common pathological condi­tions like:

1. Infections (pneumonia, sepsis, meningitis, erysipeloid): leucocytosis absence in infectious process acute phase is considered to be unfavorable diagnostic criterium especially at combination with so-called leucocytic formule shift to the left – see below

2. Allergy

3. Common cold

4. Tuberculosis and

5. Glandular fever

6. Nausea and vomiting – with primarily neutrophils amount increasing

7. Inflammatory processes in part at their purulent character

8. Different organs (myocardium, lungs, spleen, kidney) infarction

9. Vast burnings

10. Bleedings

11. Malignant diseases

12. Blood system diseases (leucosis, polycytemy, lymphogranulomatosis)

13. Infectional mononucleosis and lymphocytosis

14. Uremia

15. Diabetic coma

16. After splenectomy (expressed leucocytosis 15…20 x 10⁹/l with neutrophyly up to 90%)

However, different leukocyte count is increased in specific diseases as given below.

Neutrophilia

The increase in neutrophil count is called neutrophilic leukocytosis. This occurs in the following conditions:

1. Metabolic disorders

2. Injection of foreign proteins

3. Injection of (foreign) vaccines

4. Poisoning by chemicals and drugs like lead, mercury, camphor, benzene derivatives, etc.

5. Poisoning by insect venom and

6. After acute hemorrhage.

Eosinophilia

The increase in eosinophil count is called eosinophilia and this occurs in:

1. Allergic conditions

2. Asthma

3. Blood parasitism (malaria, filariasis) and ascaridosis

4. Intestinal parasitism and

5. Scarlet fever

6. Tumors

7. Lymphogranulomatosis

8. Chronic myeloleucosis

9. Medicines (antibiotic, sulphanilamides in part)

Basophilia

Increase in basophil count is called basophilia and it occurs in:

1. Smallpox

2. Chicken pox and

3. Polycythemia vera

4. Allergic processes accompanied by rash

5. Before and during menstrual bleeding

6. Stress

7. Leucosis

8. Myocardial infarction

Monocytosis

Increase in monocytes count is known as monocytosis and occurs in:

1. Chronic infections (tuberculosis, syphilis, brucellosis)

2. Acute infections (rubeole, scarlet fever, infectious parotitis, mononucleosis)

3. Lymphogranulomatosis

4. Endocardites

5. Helminthes

Limphocytosis

1. Increase in lymphocyte count is called lymphocytosis and this occurs in:

2. Diphtheria

3. Infectious hepatitis

4. Mumps

5. Malnutrition

6. Rickets

7. Syphilis

8. Thyrotoxicosis and

9. Tuberculosis

Leukemia

The leukemia is the condition, which is characterized by abnormal uncontrolled increase in leukocyte count up to 1,000,000/cu mm.

LIFESPAN OF WHITE BLOOD CELLS

Lifespan of white blood cells is not constant. It depends upon the demand in the body and their function. Lifespan of these cells may be as short as half a day or it may be as long as 3-6 months.

However, the normal lifespan of white blood cells is as follows:

Neutrophils —	2-5 days
Eosinophils —	7-12 days
Basophils —	12-15 days
Monocytes —	2-5 days
Lymphocytes —	1 day

Table 4. White Blood Cells Lifespan

PROPERTIES OF WHITE BLOOD CELLS

1. Diapedesis

Diapedesis is the process by which the leukocytes squeeze through the narrow blood vessels.

2. Ameboid Movement

Neutrophils, monocytes and lymphocytes show amebic movement by protruding into the cytoplasm and changing the shape.

3. Chemotaxis

A number of chemical substances in the tissues cause the leukocytes to move towards tissues. This phenome­non is called chemotaxis.

4. Phagocytosis

Neutrophils and monocytes swallow foreign bodies by means of pseudopodia.

FUNCTIONS OF WHITE BLOOD CELLS

NEUTROPHILS - are produced in bone-marrow, live 8-10 hours, part of them are in circulation, another one – into marginal state and significant part leaves blood and dies in tissues.

Neutrophils play an important role in the defense of the body. Along with monocytes, the neutrophils provide the first line of defense against the invading microorganisms. The granules of neutrophils contain enzymes like proteases, myeloperoxidases, elastases and metalloproteinases. The granules also contain antibody like sub­stances called defensins. Defensins are antimicrobial peptides, which are active against bacteria and fungi. Neutrophils also secrete platelet activating factor (PAF) which accelerate the aggregation of platelets during injury to the blood vessel.

Mechanism of Action of Neutrophils

Neutrophils are released in large number from the blood at the time of infection by the foreign microorganisms. At the same time, new neutrophils are produced from the progenitor cells. All the neutrophils move by diapedesis and are attracted towards the site of infection by means of chemotaxis. The chemotaxis occurs due to the attraction by some chemical substances called chemo-attractants, which are released, from the infected area. After reaching the area, the neutrophils surround the area and get adhered to the infected tissues. The chemo-attractants increase the adhesive nature of neutrophils so that all the neutrophils become stickier and get attached firmly to the infected area. Now, the neutrophils start destroying the invaders. First, these cells engulf the bacteria and then destroy them by means of phagocytosis. Each neutrophil can hold about 15-20 microorganisms at a time. During the battle against the bacteria, many leukocytes are also killed by the toxins released from the bacteria. The dead cells are collected in the center of infected area. The dead cells together with plasma leaked from the blood vessel, liquefied tissue cells and red blood cells escaped from damaged blood vessel (capillaries) constitute the pus. The dead white blood cells are called the pus cells.

Functions:

• participating in phagocytosis;

• apoptosis triggering;

• interleukines-1,6,8 and 12 formation;

• interpheron formation;

• immune reactions;

• participation in mitosis;

• reparational and regenerational processes;

• hematopoietic reactions;

• blood coagulation;

• fibrinolysis (they contain plasminogen activator).

EOSINOPHILS - are produced in bone-marrow, live from 4 to 12 days. They are only several hours in blood stream, then penetrate into the tissue for destruction.

Functions:

• phagocytosis;

• antitoxic function;

• kallikrein-kinin system components activation.

Eosinophils are specifically meant for acting against the parasites. The eosinophil count increases during parasitic infestations and allergic conditions. Rose sundown of speedy recovery after infectious pathology - eosinophyly – is a very favorable and long-awaited diagnostic criterium. Eosinopeny – their amount decreasing - is observed at hard infectional diseases – unfavourable diagnostic sign.

Mechanism of Action of Eosinophils

The eosinophils are neither markedly motile nor phagocytic like the neutrophils. But their granules contain mar, substances, which become cytotoxic when released during the invading organisms. Following are the lethal substan­ces present in the granules of eosinophils and release; at the time of exposure to parasites or foreign proteins

1. Eosinophil peroxidase: This enzyme is capable destroying helminthes (worms), bacteria and turned cells.

2. Major basic protein (MBP): This is very active against helminthes. It can damage the parasites by distension (ballooning) and detachment of the teg­mental sheath (skin like covering) of these organism

3. Eosinophil cationic protein (ECP): This substances the major destroyer of helminthes. It destroys the parasite by means of complete disintegration. It is also acts as neurotoxin.

4. Eosinophil derived neurotoxin: it destroys the nerve fibers particularly the myelinated nerve fibers.

BASOPHILS - are formed in bone-marrow, live up to 12 hours. Their relatives - fat cells (mast cells, mastocytes) live for years.

The basophils play an important role in healing process after inflammation and in acute hypersensitivity reactions (allergy). The number of basophils is increased during healing process and right before menstruation (especially in sexual organs vessels).

Mechanism of Action of Basophils

The functions of basophils are executed by the releasing of some important substances from their granules.

1. Histamine: It produces the acute hypersensitivity reactions by causing vascular changes and by increasing the capillary permeability.

2. Heparin: Heparin is essential to prevent the intravascular blood clotting.

3. Hyaluronic acid: This is necessary for deposition of ground substances in the basement membrane. It participates in membrane permeability increasing.

4. Proteases and myeloperoxidase: These enzymes may exaggerate the inflammation responses.

5. Platelets activation factor synthesis.

6. Thromboxanes production – see next lection.

7. Leucotryens – participate in multiple organism reactions.

8. Prostaglandines – the same + next lecture.

The basophils also have IgE receptors, which het; them to produce hypersensitivity responses.

It is necessary to mention that eosinophils can reduce allergy reactions because they contain histaminase – histamine-decomposing enzyme. There is so-called eosinophylic-basophylic association – parallel increase of basophils and eosinophils. It can be observed at allergy latest stages. And if it is so – it is considered as a favorable prognostic criterium for the patient.

Mast Cell

Mast cell is a large tissue cell resembling the basophil is present in bone marrow and around the cutaneal blood vessels but does not enter the circulation.

The mast cell plays an important role in producing hypersensitivity reactions like allergy and anaphylaxy. It secretes heparin, histamine, serotonin, and hydrolytic enzymes.

MONOCYTES – are formed in different hemopoietic organs:

• bone marrow,

• lymphatic nodes;

• connective tissue.

Life duration – 36-104 hours. They leave tissues and form macrophagal family there.

Role:

• strong phagocytosis;

• contain monokines influencing on lymphocytes;

• antiinfectional action;

• antitumorogenic activity;

• blood coagulation;

• fibrinolysis;

• complement system components synthesis.

Monocytes play an important role in defense of the body. Along with neutrophils, these leukocytes constitute the first line of defense. Like neutrophils, the monocytes are also motile and phagocytic. The monocytes are the free cells in the body and wander freely through the tissue. Like neutrophils, practically no part of the body is spared by monocytes.

Monocytes secrete interleukin-1 (IL-1), colony stimu­lating factors (CSF) and platelet activating factor (PAF).

Monocytes are the precursors of the tissue macropha­ges. The matured monocytes stay in the blood only for few hours. Afterwards these cells enter the tissues from the blood and become tissue macrophages. Examples of tissue macrophages are Kupffer cells in liver, alveolar macrophages in lungs and macrophages in spleen.

LYMPHOCYTES

The lymphocytes play an important role in immunity. Functionally, the lymphocytes are classified into two categories namely, T lymphocytes and B lymphocytes. T lymphocytes are responsible for the development of cellular immunity and B lymphocytes are responsible for the development of humoral immunity. T-lymphocytes are thymus-dependent. Their processing in thymus occurs mostly during the period between just before birth and few months after birth. Thymosin is a hormone secreted by thymus and released into circulation. Thymosin also plays an important role in immunity. It accelerates the proliferation and activation of lymphocytes in thymus. It also increases the activity of lymphocytes in lymphoid tissues.

There one of their population comes to thymus where their differentiation in T-lymphocytes takes place. Other part – to bursa of Fabricius analogue (in birds) in small intestine cellular formations, tonsills, appendix, bone marrow and are differentiated in lymphocytes (bursa-dependent). The bursa of Fabricius is a lymphoid organs situated near the cloaca of birds. The bursa is absent in mammals, and the processing of B lymphocytes takes place in bone marrow and liver. This lymphocytic part is not differentiated in immune organs and such lymphocytes are called zero-lymphocytes (neither T-, nor B-).

T-lymphocytes have several types:

• helpers or inducers;

• cytotoxic or killers;

• suppressors;

• memory.

In a whole, they are responsible for cellular immunity. Their amount is 40-70 per cent of all lymphocytes amount.

Storage of T Lymphocytes

After the transformation, the various types of T lympho­cytes leave the thymus, migrate and stay in the lymphoid tissues present in lymph nodes, spleen, bone marrow and the gastrointestinal tract.

B-lymphocytes also have several types:

• plasma cells;

• memory cells.

According to another classification – subsets like T-lymphocytes.

They provide immunoglobulins formation (B-lymphocytes are transformed into plasmocytes – producers of these molecules) and thus delt with cellular and especially with humoral immunity. Their amount is 20-30 per cent of all lymphocytes.

Storage of В Lymphocyte

After the transformation, В lymphocytes migrate and stay in the lymphoid tissues present in lymph nodes, spleen, bone marrow and the gastrointestinal tract.

Zero-lymphocytes secrete proteins (perphorines) possessing the ability to make the foramen in side cells membrane and while protheolytic enzymes (cytolysines) pouring in them destroy them. That’s why they are often named as natural killers. Their amount is 10-20 per cent of all lymphocytes.

Leucocytic formula:

• basophils – 0-1,0 %;

• eosinophils – 1,0-4,0 %;

• neutrophils - 50,0-70,0 % - among them:

• juveniles – up to 1,0%,

• rod or stab neutrophils (rods or stabs) – 1,0-4,0 %,

• segs or segment-nuclear neutrophils – 50,0-65,0 %;

• lymphocytes – 25,0-40,0 %;

• monocytes – 2,0-10,0%.

Movement (shift) to the left - is called regenerative movement (blood renewal, sign of so-called young blood); is characterized by juveniles and rod (stab) neutrophils increasing in blood. Reasons:

• infectional diseases;

• leucoses;

• inflammational processes.

Movement (shift) to the right - is called degenerative movement (sign of old blood): is characterized by juveniles and rod (stab) neutrophils amount decreasing and segment- nuclear leucocytes number increasing. It may be observed at:

• aplastic anemias;

• leucoses.

LEUCOPOIESIS REGULATION

Like erythropoiesis regulation it can be performed both specific and non-specific ways. Specific way – is leucopoietins action (they are produced into liver, spleen, thymus, kidneys). Their action mechanism is in involving into bone marrow cells differentiation process. Non-specific way – is:

1. vitamin’s action (especially of groups “B₁₂” and “C”);

2. hormones:

• ACTH;

• thyroid;

• sexual;

3. microelements;

4. leucocytes, tissues, toxin’s, microbes metabolic products have special importance for leucopoiesis regulation. The more leucocytes are destroyed, the more new forms are formed.

67. 

FIGURE 7: Leucopoiesis

The committed pluripotent stem cell gives rise to colony forming unit and lymphoid stem cell.

COLONY FORMING UNIT

Different colony forming units are:

1. Colony forming unit—Erythrocytes (CFU-E)

2. Colony forming unit—Granulocytes and Monocytes (CFU-GM)

3. Colony forming unit—Megakaryocytes (CFU-M)

DEFINITION AND TYPES OF IMMUNITY

Resistance of the body against the pathogenic agents is known as immunity. It is the ability of the body to resist different types of foreign bodies like bacteria, virus, toxic substances, etc. which enter the body. Immunity is of two types namely, innate immunity and acquired immunity.