1. Types of leukocytes

2. Production (Leukopoiesis )

3. Functional characteristics of the

different leukocytes

4. Mechanisms: How do they do

what they do?

Lecture topics: characteristics and functions of WBCs*

Leukocytes

• Only formed elements that are complete cells with a nucleus and cytoplasmic organelles.

• On average, there are 4000-10000 WBC/l of blood. Average no.=7000 l of blood

• Remember they account for about 1% of total blood cells.

• Leukocytosis: An increase in no. of WBCs in circulation.

- specific WBC type: lymphocytosis, granulocytosis, neutrophilia.

• Leukopenia: A decrease in no. of circulating WBCs.

Types of leukocytes**

1. Neutrophils………62%

2. Eosinophils………2.3%

3. Basophils…………0.4%

4. Monocytes………..5.3%

5. Lymphocytes……..30%

Polymorphonuclear

Or granulocytes

Note: To remember the order of abundance leukocytes from most

abundant to least abundant: Never Let Monkeys Eat Bananas

**granulocytes and monocytes protect body by ingestion (phogocytosis) of

invading organisms( for example bacteria). They are formed in bone marrow.

** lymphocytes protects body through immune system. They are formed in

lymphogenous tissues (lymph glands, spleen, tonsils, thymus, Peyer‟s patches in

intestinal wall.

agranulocytes

Genesis of WBCs (leukopoiesis)

Pluripotential

stem cell

lymphoblast myeloblast

neutro eosino

baso mono

T

lympho B

lympho Plasma cell

Life span of WBCs*

• Granulocytes stay in blood for 4-8 hours and in the tissues 5 days. When there is serious infection their whole life span is shortened to few hours

• Monocytes stay in the blood for 10-20 hours and then they leave to different tissues where they form tissue macrophages. Tissue macrophages can live for months. If there is infection these macrophages may die earlier.

• Lymphocytes circulate between blood and lymphoid tissues through lymph and they survive for weeks and months

Neutrophils and macrophages

defend against infection

Macrophage : Monocytes in the

blood then in the tissues swell

and increase the diameter and

become

Leukocytes cross capillary wall by

Diapedesis

Diapedesis – Leukocytes able to slip out of the

capillary. They sequeeze themselves through small pore between endothelial cells that form the capillary wall.

– All leucocytes can make this movement between blood and interstitial space.

Note: diapedesis is increased in inflammation. Factors released from inflamed tissues make WBCs to stick to the capillary wall in inflamed tissue (this effect is

called margination). And this increases diapedesis.

Amoeboid motion of Leukocytes

– leukocytes move through the tissue spaces

through this motion.

– They form cytoplasmic extensions that move them along (pseudopods). These pseudopods also help WBC to phogocytize foreign particles.

Movement of WBCs by Chemotaxis towards an

area of tissue damage

• Chemical substances

(chemotactic substance, chemotaxins) found and produced in the tissues or released by other leukocytes that attract WBCs toward these chemicals.

• Chemotaxins include

1. Bacterial or viral toxins

• Degenerative products of inflamed tissues

• Reaction products of „complement complex‟

• Reaction products of plasma clotting

Chemotactic signals effective till 100m

Opsonization

• Plasma factors act on the bacteria to make them

„tasty‟ to the Phagocytes. It enhances the

phagocytic ability of WBCs

• Opsonins which coat the bacteria are IgG and

Complement proteins

• Coated bacteria bind to receptors on the

Neutrophil membrane.

bacteria

Phagocytosis

• Means ingestion of invading agents (bacteria, viruses,

foreign bodies, dead tissues). Done mostly by

macrophages and neutrophils (neutrophils can

phagocytize 3-20 bacteria and macrophages

can phagocytize up to 100 bacteria)

• 1. Selective – Natural structures is protected from

phagocytosis by smooth surface and protective proteins.

While foreign bodies have rough surfaces and no

protective proteins so they are liable to be phagocytized.

• 2. Antibodies adhere to surface of bacteria and make

them susceptible for phagocytosis (opsonization).

Phagocytosis by neutrophils and

macrophages • Phagocytized particles digested by intracellular

enzymes

• Neutrophils and Macrophages have proteolytic enzymes.

• Macrophages (but not neutrophils) have

lipases which can digest lipid membrane surrounding some bacteria (Tuberculosis bacilli)

• Macrophages are more powerful phagocytes than neutrophils. They can engulf large particles and digest them and extrude the residual products of digestion so they survive after so many phogocytosis process.

Phagocytosis process • The WBC sends pseudopods around foreign particle and making a

enclosed chamber that contains the particle forming phagocytic vesicle (called phagosome).

• Lysosomes containing digestive enzymes fuse with phagosome which is called now digestive vesicle. The particle is digested and residual products are thrown outside WBC.

Phagocytosis (cont.)

• Neutrophils and Macrophages produce

Oxidizing agents which are bactericidal (killing

bacteria) e.g. Super oxide(O2-), Hydrogen

peroxide(H2O2), hydroxyl ions

• Myeloperoxidase is lysosomal enzyme which

can convert chloride to form hypochlorite which

is very strong bactericidal agent.

Note: O2- and H2O2 are Oxidants and Bactericidal

Reticuloendothelial system RES:

Monocytes, Mobile macrophage,

fixed macrophage, spleen, lymph

nodes and specialized endothelial

cells in the bone marrow (all

originated from monocytic stem

cells)

RES is used in medical terms than

monocyte macrophages system as

they are synonymous

Special macrophages are present

in :

1. Skin, subcutaneous tissues

2. Lymph nodes

3. Alveolar macrophages in the

lungs

4. Macrophages (Kupffer cells) in

the liver

5. Macrophages in the spleen and

bone marrow

Eosinophils

• About 2% of all leukocytes

• Ineffective protection against usual types of infection.

• Contain large granules that stain red.

• About the same size as neutrophils but weaker phagocytes

• nucleus has 2 lobes

Eosinophils (cont.) • Eosinophils no. is increased in

people with parasite infection (like worms)

– Release the enzymes (hydrolytic enzymes, highly reactive form of oxygen, major basic protein) from their cytoplasmic granules onto the parasite‟s surface, killing the parasites .

• Eosinophils are attracted by chemotactic factor released by basophils and mast cells toward allergic tissues.

• They detoxify the substances that released during allergic reaction. Also they engulf antibodies-antigens complexes so they help in reducing spread of allergic reaction

Basophils

• Large histamine-containing granules

– Affinity for basic dyes so they stain purplish black (baso = basic).

• Similar in function to mast cells. Mast cells are found in the tissues.

• Both mast cells and basophils liberate histamin and heparin, small quantities of bradykinins and serotonin.

Basophils

• Basophils and mast cells play important role in allergic

reactions.

• IgE attached to surface of basophils and when antigen bind

with IgE on the surface, degranulation follows this binding

and release of histamine, bradykinin, serotonin, Slow

Reactive Substance of Anaphylaxis, heparin and other

lysosomal enzymes

antigen

Agranulocytes

• Lack visible cytoplasmic granules

• Include lymphocytes and monocytes

B lymphoctes

– Attack bacteria, viruses and toxins and converted into

a. Plasma cells that produce antibodies (Ig = immunoglobulin)

b. Memory cells

• Keep a “record” of pathogens

monocyte

T Lymphocytes

• T cells

– Acting directly against

virus-infected cells and

tumor cells

1. CD 4

• T helper cells

2. CD 8

• T cytotoxic cells

3. suppressor T cells

1. T Helper cells : (AIDS) The most

numerous type of T cells. They help in

the function of immune system ,

forming protein mediators called

lymphokinase

which cause:

a. Stimulation of growth and

proliferation of cytotoxic and

suppressor T cells

b. Stimulation of B cells growth and

form plasma cells and antibodies.

c. Activation of macrophage

system.

d. Feedback stimulatory effect

on the T helper cells (positive

feedback effect

2. Cytotoxic cells : Killer cells,

direct attack

3. Suppressor cells: Limiting the

ability of immune system to

attack a person‟s own body

tissues (Immune tolerance)

Monocytes

• They have abundant pale-blue cytoplasm and a darkly staining purple nucleus, which is distinctively U or kidney shaped

• Migrate from blood into tissues where they enlarge and become macrophages (which are phagocytic).

Most powerful phagocyte

They can phagocytize whole

RBC, malarial parasites and

dead neutrophils

They are very important in

starting immune responses

They can be called different

names when they stay in

different tissues.

•Skin…..histiocytes

•Lungs...alveolar macrophage

•Liver….Kupffer cells

Plasma cell

A type of immune cell that

makes large amounts of a

specific antibody. They are

develop in the bone marrow

from B cells that have been

activated.They are transported

by plasma and lymphatic

system

Mast cell: Originate from bone marrow

(Monocyte or lymphocytes??),

very similar to basophil.

Found widely in the body

particularly in connective tissues.

They produce histamine, Heparin,

serotonin,

Dopamine and also involve in the

immunological, allergic and

inflammatory conditions.

Leukocytosis: An increase in no. of WBCs in circulation.

- specific WBC type: lymphocytosis, granulocytosis, neutrophilia.

Leukopenia: A decrease in no. of circulating WBCs. Irradiation, Xray or gamma rays. Drugs, chloramphenicol, thiouracil , borbiturate hypnotics

Leukemia :

Uncontrolled production of WBC

1.Lymphocytic (Lymph nodes)

2. Myelogenous (Bone marrow)

Effects of leukemia:

Infection, Sever anemia,

Bleeding tendency, Excessive

use of metabolic substrate by

cancerous cells cause deblitate

of other tissues.

Role of macrophage and

neutrophils in inflammation

• When bacteria get access to certain tissue, the first line of defense is macrophages which are already in that tissue.

• Within hour or so, the no. of neutrophils starts to increase in the area. Neutrophils form the second line of defense.. These neutrophils come from blood due to liberation of chemotactic substances.

Role of macrophage and

neutrophils in inflammation (cont.)

• In severe infection the no. of neutrophils

(neutrophilia) in the blood increases

dramatically 3rd. Products of inflammation

stimulate bone marrow to release the

stored neutrophils there in bone marrow

4th.

( remember that bone marrow stores of

WBCs is more that no. of WBCs in the

blood).

Role of macrophage and

neutrophils in inflammation (cont.)

• Monocytes from blood enter the site of

inflammation and become active

macrophages in few days.

• Factors (Substances) released from

activated macrophages stimulate bone

marrow to produce new monocytes and

neutrophils.

Role of macrophage and

neutrophils in inflammation (cont.) • Monocytes from blood

enter the site of inflammation and become active macrophages in few days.

• Factors (Substances) released from activated macrophages stimulate bone marrow to produce new monocytes and neutrophils.

Activated

macrophage

Releasing

1.TNF (tumor necrosis factor

2. GM-CSF (granulocyte monocyte colony stimulating

factor

3. M-CSF (monocyte colony stimulating factor

4. G-CSF (granulocyte colony stimulating factor

Granulocytes, monocytes

Role of macrophages in activation of

lymphocytes

• When macrophage phagocytize invading microorganisms and digest them, the antigenic products liberated into macrophage cytoplasm. Macrophages pass these antigens directly to lymphocytes leading to activation of specific lymphocytes that can make proper immune reaction against invading microorganism.

• Also macrophages produce substance (interleukin-1) that stimulates growth and reproduction of specific lymphocytes.

macrophage lymphocyte

bacteria

Character of inflammation

•Vasodilatation, permeability, interst fluid

clotting, increase no of granulocyte and

monocyte, swelling of the tissue.

•Tissue product: Histamine, bradykinin,

serotonin, prostaglandin.

•(Walling off) effect of inflamation.

Feedback control of neutro and

macro

TNF, Interleukin 1(IL-1), GM-CSF, M-CSF,

G-CSF

These factors are formed by activated

macrophages in the inflamed tissues

Formation of pus

Neut and Macro engulf bacteria

and necrotic tissues then Neut

and macro die and cavity

formed in the inflamed tissue.

This cavity contains necrotic

tissue, dead Neut, dead Macro

and tissue fluid. This mixture

known as pus