Lec 06 : LeukocytesStructure, Function, Production & Destruction

Assist. Prof. Dr. Mudhir S. Shekha

Learning Objectives

• Describe the general characteristics of leukocytes

• Classify leukocytes according to their lineage, their main structural features, and their primary functions

• Leukopoiesis

White blood cells

• Why leucocytes called white cells?

• WBC: mobile units of the body's protective system.

• Normal count is 4000-11,000 /µL

• Have nuclei and other organelles

• Defend the body against pathogens

• Remove toxins, wastes, and abnormal or damaged cells

• Are capable of amoeboid movement (margination) and positive chemotaxis

• Some are capable of phagocytosis

Concept of pool

• There are 3 different areas in our body where different WBCs reside

1. Marrow pool: →90% neutrophils

2. Blood pool:→ 3%

3. Tissue pool: →7%

Life span

• Granulocytes:→ 4-8 hours in circulation, 4-5 days in tissues.

• Monocytes: →10-20 hours in blood, months in tissue (tissue macrophages)

• Lymphocytes→ live for weeks or months.

• They originate in the bone marrow and circulate throughout the lymphoid tissues of the body.

White Blood Cells

Function Of WBC• 1) Scavenging: At the site of injury or infection,

neutrophils in blood and monocytes in the tissue engulf worn out cells of the body and dead microbes and thus act as scavengers.

• 2) Diapedesis: Neutrophils show amoeboid movement. They migrate towards the site of infection, squeeze through capillary walls to engulf and kill microbes.

• 3) Pus formation: At the site of infection, WBCs phagocytize invading microorganisms and dead cells. These accumulate in the infected area together with exuded plasma. The dead leucocytes along with destroyed tissue cells, dead and live microbes and exuded plasma form the pus.

• 4) Phagocytosis: On reaching site of infection, neutrophils and monocytes engulf microbes or foreign matter or the damaged cells. This is called phagocytosis. By phagocytosis, neutrophils kill microorganisms and protect the body against infections.

• 5) Inflammation or Inflammatory Reaction: Inflammation is swelling caused at the site of injury. The blood vessels at this point release more blood making it red and hot. Due to accumulation of tissue fluid, the area swells up. The neutrophils and macrophages migrate through capillary wall by diapedesis and fight against invading microbes.

• 6) Formation of Antibodies: Lymphocytes produce antibodies to kill germs and neutralise their toxins (poisons produced by bacteria).

• 7) Confer Immunity: Lymphocytes also produce antibodies to provide life long immunity against certain diseases.

Granulocytes• Granulocytes are granule-containing WBCs.

They have lobed nuclei, which typically consist of several rounded nuclear areas connected by thin strands of nuclear material. The granules in their cytoplasm stain specifically with Wright's stain. The granulocytes include the neutrophils, eosinophils and basophils.

Neutrophils

1. Cell size→ 12–15 micrometers (µm)

2. Nucleus→ central or eccentric; 2-6 lobes; deep purplish blue

3. Cytoplasm- faint pink

4. Granules- fine(pin-point); violet pink in color

• most abundant→(≈1011 /day) → 50-70% of WBC.

• Lifespan is about 5.4 days

• Neutrophils are phagocytes, capable of ingesting microorganisms or particles

Types of Granules

• Primary/ Azurophilic granules:

• Secondary /Specific/peroxidase negative granules:

• Tertiary granules:

• Secretory Granules:

Phagoytosis by neutrophils• Also called polys: first line of

defense in bacterial infections.

• Mature cells that can attack and destroy bacteria even in the circulating blood (innate immune).

• Attach to the particle and project pseudopodia around it→ an enclosed chamber that contains the phagocytized particle which breaks away → free floating phagosome.

• Can phagocytize 3-20 bacteria before it dies.

Eosinophil1. Cell size- 10-14µm

2. Nucleus- central or eccentric;

3. 2-3 lobes; purplish blue; “spectacle shaped”

4. Cytoplasm- full of granules , acidophilic; bright pink in color

5. Granules- large; coarse; crimson red

6. 1-6% of white blood cells

• Eosinophils primarily deal with parasitic infections. Eosinophils are also the predominant inflammatory cells in allergic reactions.

• The most important causes of eosinophilia include allergies such as asthma, hay fever, and hives.

Eosinophils persist in the circulation for 8–12 hours, and can survive in tissue for an additional 8–12 days in the absence of stimulation.

Basophil1. Cell size- 10-14µm 2. Nucleus- central; 2-3 lobes; purplish blue; overlaid

with granules 3. Cytoplasm- basophilic; full of granules 4. Granules- very coarse, deep purple or blue5. 0.01% to 0.3% of circulating white blood cells

• Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histaminecausing vasodilation.

• Similar to mast cells outside capillaries in connective tissue. Both basophils and mast cells release heparininto blood, which prevent blood coagulation.

Agranulocytes• Agranulocytes lack visible cytoplasmic granules.

Their nuclei are spherical oval or kidney-shaped. The agranulocytes include lymphocytes and monocytes

Lymphocyte

• Cell size- LL:12-16µm; SL:7- 10µm

• Nucleus- eccentric; large round nucleus; deep purplish blue

• Cytoplasm- scanty; light blue color

• Differential:2 0-40% (Absolute: 1500-4000/µl of blood)

• Lymphocytes are much more common in the lymphatic system.

• B lymphocytes: Processed in bone marrow. When exposed to an Ag, they differentiate to plasma cells that produce antibodies (gamma globulins). This initiates the destruction of the antigen.

T cells: Processed in thymus. They release chemicals that destroy target cells with which they make contact such as virusinfected cells and cancer cells.

• CD4+ helper T cells: →MHC II complex on APC. →coordinate the immune response.

• CD8+ cytotoxic T cells: →MHC I complex of virus-infected or tumour cells and kill them.

• Natural killer cells are able to kill cells of the body that have lost MHC I molecule, as they have been infected by a virus or have become cancerous.

Monocyte

1. Cell size- 12-20µm 2. Nucleus- eccentric or central; round or oval; pale

bluish violet 3. Cytoplasm- abundant; pale blue; clear4. Differential: 2-10% (Absolute:500 -800/µl of blood)

• Monocytes share the "vacuum cleaner" (phagocytosis) function of neutrophils, but are much longer lived as they have an additional role.

• they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed, or so that an antibody response may be mounted.

Monocyte

• Monocytes eventually leave the bloodstream to become tissue macrophages, which remove dead cell debris as well as attacking microorganisms. Neither of these can be dealtwith effectively by the neutrophils.

• Unlike neutrophils, monocytes are able to replace their lysosomal contents and are thought to have a much longer active life.

Phagocytosis by monocytes• Immature in blood (1-2 days)

• In tissues → mature and enlarge → tissue macrophages.

• Much more powerful phagocytes than neutrophils.

• Can phagocytize as many as 100 bacteria.

• Can engulf large particles e.g. malarial parasites.

• Can survive after phagocytosis for months.

2nd Year Medicine- IBLS Module

May 2008

Genesis of the Leukocytes (leucopoiesis)

• The process of development and maturationof white blood cells(leucocytes), is called leucopoiesis.

• Aside from those cells committed to the formation of red blood cells, two major lineages of white blood cells are also formed, the myelocytic and the lymphocyticlineages. The lymphocytic lineage beginning with the lymphoblast; that produce lymphocytes, and the myelocytic lineage beginning with the myeloblast; which produce other WBCs.

• The granulocytes and monocytes are formed only in the bone marrow. Lymphocytes are produced mainly in the various lymphogenous organs, including the lymph glands, the spleen, the thymus, the tonsils, and various lymphoid rests in the bone marrow, gut, and elsewhere.

Genesis of the Leukocytes (leucopoiesis)

• Like erythrocyte production, the formation of

leukocytes and platelets is stimulated by

hormones. These colony stimulating factors

(CSFs) and interleukins not only prompt red

bone marrow to turn out leukocytes, but

enhancing the ability of mature leukocytes

to protect the body.

MYELOID SERIES

HEAMOCYTOBLAST

MYELOIDSTEM

CELL

MYELOBLAST

PROMYELOCYTE

MYELOCYTE

METAMYELOCYTE

BAND FORM

GRANULOCYTE

GRANULOPOIESIS

HEAMOCYTOBLAST

MYELOID STEMCELL

MYELOMONOBLAST

PROMONOCYTE

MONOCYTE

(BLOOD)

MACROPHAGE

(TISSUES)

FORMATION OF

MONOCYTES

MONOCYTE-

MACROPHAGESERIES

HEAMOCYTOBLAST

LYMPHOID STEMCELL

LYMPHOCYTE

PLASMACELLS

LYMPHOBLAST

LYMPHOPOIESIS

PROLYMPHOCYTE

Regulation of leucopoiesis Granulopenia or dead

granulocytes & monocytes

G-CSF

M-CSF

GM-CSF

Interleukins (monocyte)

Bone Marrow

Granulocytes

Monocytes/macrophages

Normalcounts inhibit

Stimulate

Increased formation

Releases

monocytes & T lymphocytes

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