Leucocyte(WBC)

Introduction Crucial in the body’s defense against

pathogens

These are complete cells, with a nucleus and organelles

They lack Hb so they are colorless

They are formed partially in the bone marrow and partially in the lymph tissue

Types of Leucocytes Granulocytes

Granules in their cytoplasm which can be stained

Biologically active substances involved in inflammatory and allergic reactions.

Neutrophils, Eosinophil, and Basophils

Agranulocytes

Lack visible cytoplasmic granules

Lymphocytes and Monocytes

Leucocytes

Granulocytes

Eosinophil1-6 %

Basophil0-1%

Neutrophil40-75%

Agranulocytes

Monocytes2-10%

Lymphocytes 20-40%

Polymorphonuclear WBC

How to remember WBC ranking? Never Let Monkeys Eat Bananas

Types of LeucocytesGranulocytes

Agranulocytes

Neutrophil Eosinophil Basophil

Monocyte Lymphocyte

Leukocyte Levels In The Blood Normal levels =4,000 to 11,000 cells/mm3

Abnormal leukocyte levels Leucocytosis

Above 11,000 leukocytes/mm3

Generally indicates an infection

Leucopenia Abnormally low leukocyte level < 4000/mm3

Commonly caused by certain drugs

Leukemia Abnormally high (~>80,000) and immature

leucocytes.

Leucocytosis VSLeukemoid reaction VS

Leukemia

Leukopoiesis

Genesis of WBC.

The granulocytes and monocytes are formed only in the bone marrow.

Lymphocytes and plasma cells are produced mainly in the various lymphogenous tissues—especially the lymph glands, spleen, thymus,

Myeloblast

Lymphoblast

Myeloblast

promyelocyte

Young neutrophil metamyelocyte

Neutrophil myelocyte

Band neutrophil metamyelocyte

neutrophil

Basophil myelocyte

Eosinophilmyelocyte

Eosinophilmetamyelocyte

eosinophil basophil

monoblast

promonocyte

monocyte

Lymphoblast

prolymphocyte

lymphocyte

NeutrophilSize:10-14 µm in diam.Nucleus:

1. Multilobed (1-6 lobes) therefore called polymorphnuclear leucocytes.

2. Young cell have single horse shoe shaped nucleus.

average half-life in the circulation is 6 hours

Neutrophil4 types of granules are present1. Primary/ Azurophilic granules:

Contains :

myeloperoxidase, (produces HOCl for killing

bacteria).

acid hydrolases, which can digest bacteria,

elastase, proteinase, α-1 antitrypsin

Antimicrobial proteins like cathepsin-G,

Defensins- α, β

2. Secondary /peroxidase negative granules:more numerous. Contain

Lactoferrin-antibacterial

Gelatinase, lysozyme- microbicidal, Vit B12

binding protein &

Components of enzyme system that produce free radicals like H2O2, which kills the microbes.

Substances that facilitates chemotaxis.

3. Tertiary granules: Gelatinase, alkaline phosphatase and cytochrome-b

4. Secretory Granules: secretory vesicles contain CD3, phospholipase and tyrosine kinase

Functions of Neutrophil Functions:1. Phagocytosis:2. Reaction of inflammation: release

leukotrienes, prostaglandins, thromboxanes

3. Febrile Response: They contain fever producing substance, endogenous pyrogen which is an important mediator of febrile response to bacterial pyrogens

Steps of phagocytosisSteps of Phagocytosis: 1. Margination2. Diapedesis3. Chemotaxis4. Recognition and

attachment(Opsonization)5. Engulfment and creation of phagosome6. Fusion of phagosome with lysosome7. Destruction and digestion8. Residual body Exocytosis

Margination: Cytokines cause increased level of selectins

and intercellular adhesion molecule-1 (ICAM-1) on the surface of endothelial cells.

These adhesion molecules bind to complementary molecules/receptors on the neutrophil, causing it to adhere to the wall of the capil.lary or venule

Diapedesis Cytokines cause the intercellular

attachments between the endothelial cells of the capillaries and small venulesto loosen,

Neutrophils crawl through these openings directly from the blood into the tissue spaces.

A single neutrophil can usually phagocytize 3 to 20 bacteria before the neutrophil becomes inactivated and dies.

Neutrophillic Killing of Bacteria

the killing effect results from powerful oxidizing agents formed in peroxisome of neutrophils.

These oxidizing agents include large quantities of superoxide (O2−), hydrogen peroxide (H2O2), and hydroxyl ions (OH−), which are lethal to most bacteria, even in small quantities

Variation In Neutrophil Count:

A. Physiological1)After Exercise,2)After injection of epinephrine, 3)Pregnancy, menstruation,

parturition & lactation,4)Newborn,

B. Pathological1)Acute pyogenic (pus

forming) bacterial infections,

2) Acute Rheumatic feverGout

3)Following tissue destruction,

i) Burns ii) After hemorrhage, iii) poisoning by lead,

mercury,

Neutrophilia: ↑ in neutrophils>8000/mm3

Neutropenia: ↓ In Neutrophils < 1500/mm3 Typhoid fever Viral infection Malaria Aplasia of bone marrow

Eosinophils The eosinophils normally constitute about 2

percent of all the blood leukocytes.

Size:10-14 µm in diam. (2%)Nucleus:

1. Usually (85%) cells ‘bilobed’.

2. Lobes are connected with one another by chromatin threads thus producing spectacle appearance.

3. Remaining 15% cells have trilobed nucleus.

Granules1. Coarse, stain bright brick red with

acidic (eosin) dye.

2. Granules do not cover the nucleus.

3. The granules contain: histaminase, lysozymes & Major Basic Protein (MBP)

Eosinophil Function1. Mild Phagocytosis: less motile than

neutrophils

2. Parasitic infestations: Major Basic Protein- Larvicidal Eosinophil Cationic Protein- bactericidal &

major destroyer of helminths. Eosinophil Peroxidase – destruction of

helminths, bacteria & tumour cells

3. Allergic reaction: bronchial asthma & hay fever The mast cells and basophils release an

eosinophil chemotactic factor that causes eosinophil to migrate toward the inflamed allergic tissue.

Removing inflammation inducing substance like bradykinin, histamine

inhibit mast cell degranulation phagocytose & destroy Ag-Ab complexes

Specially abundant in the mucosa of respiratory tracts, GIT, urinary tract, where they provide mucosal

immunity

Variation In Eosinophil Count

Eosinophilia: ↑ in eosinophilsCauses are:-1)Allergic conditions e.g.

bronchial asthma, hay fever, filariasis

2) Parasitic infestation, trichinosis & schistosomiasise.g. worms (hookworm, roundworm & tapeworm),

3) Skin disease like utricaria.

Eosinopenia: ↓ in eosinophilsCauses are:-1) ACTH & steroid therapy2) Stressful conditions, & 3) Acute pyogenic infections

Basophils Size:10-14 µm in diam. Nucleus:

irregular bilobed shaped & its boundary is not clear because of overcrowding with coarse granules.

Granules: coarse, stain deep purple/blue Plenty, completely fill the cell &

overload the nucleus Contain:

heparin, histamine & 5HT.

Basophils function1. Mild phagocytosis2. Role in allergic reaction: Basophils release histamine, bradykinin, slow

reacting substance of anaphylaxis (SRS-A) & serotonin (5HT).

These substances cause local vascular & tissue reactions that cause many allergic manifestations.

3. Liberates heparin which Acts as anticoagulant & keeps blood in fluid

state. Activates the enzyme lipoprotein lipase which

removes fat particles from the blood after fatty meal

Variation in basophil count

Basophilia: ↑ in basophil count >100/mm3Causes are:- Viral infections, e.g. influenza,

small pox & chicken pox Allergic diseases Chronic myeloid leukemia.

Basopenia: ↓ in basophil countCauses are:-► Corticosteroid therapy, ► Drug induced reactions & ► Acute pyogenic infections

Monocytes

Size: Largest WBC 18-20 µm.Nucleus:

Is large single, eccentric in position (present on one side of the cell).

It is kidney shaped

Granules:Sometimes may contain fine purple dust like granules called Azur granules

Function of monocyte1. Role in phagocytosis:

These are powerful phagocytes & capable of phagocytosis as many as 100 bacteria. They also have ability to engulf large particles such as RBCs & malarial parasites.

2. Role in tumor immunity: kill tumor cells after sensitization by lymphocytes, play a key role in the lymphocyte – mediated immunity.

2. Synthesis of Biological Substances: Interleukin1 TNF-α, lysosomes, Proteases and Acid hydrolases

Leucopenia Condition where bone marrow produces very few

WBCs, This condition leaves the body unprotected

against many bacteria and other agents that might invade the tissues.

Cause: Irradiation of the body by x-rays or gamma

rays, or exposure to drugs and chemicals that contain

benzene or anthracene nuclei,

Effect of Leucopenia The human body lives in symbiosis with many

bacteria. Any decrease in the number of WBCs immediately

allows invasion of adjacent tissues by bacteria that are already present.

Within 2 days after the bone marrow stops producing WBCs, ulcers may appear in the mouth and colon, or some form of severe respiratory infection might develop.

Without treatment death often occur in less than a week

Leukemias

Uncontrolled production of WBCs caused by cancerous mutation of a myelogenous or lymphogenous cell is called leukemia.

Characterized by greatly increased numbers of abnormal or undifferentiated WBCs.

Classification of Leukemia The lymphocytic leukemias are caused by

cancerous production of lymphoid cells.

Myelogenous leukemia, begins by cancerous production of young myelogenous cells in the bone marrow and then spreads throughout the body.

Depending on the onset of disease it is also classified as Acute Leukemia or Chronic Leukemia

Cell Type

Lymphocyticleukemia

Myelogenousleukemia

("nonlymphocytic")

Acute

Acute lymphoblastic

leukemia(ALL)

Acute Myelogenous

leukemia(AML)

Chronic

Chronic lymphocytic

leukemia(CLL)

Chronic myelogenous

leukemia(CML)

Lymphocytic Leukemia

Myelogenous Leukemia

the more undifferentiated the cell, the more severe is the leukemia, often leading to death within a few months if untreated.

Leukemic cells, especially the very undifferentiated cells, are usually nonfunctional for providing normal protection against infection.

Effects of Leukemia on the Body

Metastatic growth of leukemic cells in abnormal areas of the body.

spread to the spleen, lymph nodes, liver, and other vascular regions

Leukemic cells from the bone marrow may reproduce so greatly that they invade the surrounding bone, causing pain and, eventually, a tendency for bones to fracture easily.

Thrombocytopenia and Anemia – displacement of the normal bone marrow cells by the non-functional leukemic cells.

Frequent infection as leukemic cells are immature to carry out immune functions.

The leukemic tissues reproduce new cells so rapidly that tremendous demands are made on the body reserves .

Tis metabolic starvation if continued long enough, alone is sufficient to cause death.