Resistance of The Body To Infection: Leukocytes, Granulocytes, The Monocyte-Macrophage System, and Inflammation

Resistance of the Body to Infection
Leukocytes, Granulocytes, the

Monocyte-Macrophage System, and Inflammation Dr Noor Kamil
ILOs
• Define the characteristics of Leukocytes

• Classification of Leukocytes
• Describe the functions of WBCs
• Explain resistance of the Body to Infection
• Discuss role of Leukocytes in inflammation
• Understand abnormalities of Leukocytes
Three Lines of Defense
Introduction
• Exposed continually to bacteria, viruses, fungi, and

parasites
• Through skin, the mouth, the respiratory passageways, the
intestinal tract, the lining membranes of the eyes, and even
the urinary tract
• Can cause serious abnormal physiological function or
even death
• highly infectious bacteria and viruses can cause acute
lethal diseases such as pneumonia, streptococcal
infection, and typhoid fever
Defense Mechanism
• Special system for combating the infectious and

toxic agents
• Composed of white blood cells (WBCs) and tissue
cells
• Cells work in two ways to prevent disease
• Destroying bacteria or viruses by phagocytosis
• Forming antibodies and sensitized lymphocytes that
may destroy or inactivate the invader
LEUKOCYTES (WHITE BLOOD CELLS)
• Mobile units of the body’s protective system

• Formed partially in the bone marrow
(granulocytes and monocytes and) and
partially in the lymph tissue (lymphocytes
and plasma cells)
GENERAL CHARACTERISTICS
• Types of White Blood Cells

• Six types of WBCs are normally present in the blood
• Granulocytes due to granular appearance by multiple nuclei
• Polymorphonuclear Neutrophils, Eosinophils, Basophils
• Agranulocytes
• Monocytes, Lymphocytes, and Plasma cells
• The granulocytes and monocytes protect the body by ingesting
invading agents (phagocytosis) or by antimicrobial or
inflammatory substances
• Neutrophils are mature and can defend in blood while monocytes
mature in the tissues increase size up to 60-80 micron
7000 WBCs per microliter
GENESIS OF WHITE BLOOD CELLS
• Myelocytic lineage, beginning with the myeloblast

• Lymphocytic lineage, beginning with the
lymphoblast
• Granulocytes and monocytes are formed only in the
bone marrow
• Lymphocytes and plasma cells are produced mainly in
• lymphogenous tissues
• lymph glands, spleen, thymus, tonsils, and lymphoid tissue and
Peyer’s patches underneath the epithelium in the gut wall
Genesis of white blood cells. The different cells of the myelocyte series are 1, myeloblast; 2, promyelocyte; 3,
megakaryocyte; 4, neutrophil myelocyte; 5, young neutrophil metamyelocyte; 6, “band” neutrophil metamyelocyte; 7,
polymorphonuclear neutrophil; 8, eosinophil myelocyte; 9, eosinophil metamyelocyte; 10, polymorphonuclear eosinophil; 11,
basophil myelocyte; 12, polymorphonuclear basophil; 13-16, stages of monocyte formation.
LIFE SPAN OF WHITE BLOOD CELLS
• Granulocytes
• 4 to 8 hours circulating in the blood and another 4 to 5 days in tissues
• Monocytes
• Short transit time, 10 to 20 hours in the blood
• In the tissues, swell to larger sizes to become tissue macrophages and live for months
unless destroyed while performing phagocytic functions
• Lymphocytes enter the circulatory system with lymph from the lymph nodes
and other lymphoid tissue
• After a few hours, they pass out of the blood back into the tissues by diapedesis
• Then they re-enter the lymph and return to the blood again and again
NEUTROPHILS AND MACROPHAGES DEFEND
AGAINST INFECTIONS
• Neutrophils and tissue macrophages attack and destroy invading
bacteria, viruses, and other injurious agents even in the circulating
blood
• White Blood Cells Enter the Tissue Spaces by Diapedesis. Neutrophils
and monocytes can squeeze through the pores of the blood capillaries
by diapedesis.
• White Blood Cells Move Through Tissue Spaces by Ameboid Motion.
• White Blood Cells Are Attracted to Inflamed Tissue Areas by Chemotaxis
• (1) bacterial or viral toxins, (2) degenerative products of the inflamed tissues, (3)
products of the “complement complex” (4) products caused by plasma clotting in
the inflamed area
Movement of neutrophils by
diapedesis through capillary pores
and by chemotaxis toward an area
of tissue damage
PHAGOCYTOSIS
• The most important function of the neutrophils and macrophages is

phagocytosis, which means cellular ingestion of the offending agent.
• First, smooth surfaces, which resist phagocytosis
• Second, protective protein coats that repel the phagocytes
• Third, antibodies against infectious agents such as bacteria
• The antibodies then adhere to the bacterial membranes and thereby

make the bacteria especially susceptible to phagocytosis
• This process by which a pathogen is selected for phagocytosis and
destruction is called opsonization
• Neutrophils can engulf 3-20 while Macrophages up to 100 bacteria
Opsonization and phagocytosis
• Once Phagocytized, Most Particles Are Digested
by Intracellular Enzymes
• Proteolytic enzymes (lysosomes of macrophages
(but not of neutrophils) also contain large amounts
of lipases)
• Neutrophils and Macrophages Can Kill Bacteria
via bactericidal agents like superoxide (O2−),
hydrogen peroxide (H2O2), and hydroxyl ions (OH −)
• MONOCYTE-MACROPHAGE CELL SYSTEM
(RETICULOENDOTHELIAL SYSTEM)
• The total combination of monocytes, mobile macrophages, fixed
tissue macrophages, and a few specialized endothelial cells in the
bone marrow, spleen, and lymph nodes is called the
reticuloendothelial system
• Tissue Macrophages in the Skin and Subcutaneous Tissues
(Histiocytes)
• Macrophages in the Lymph Nodes
• Alveolar Macrophages in the Lungs often form a “giant cell”
• Macrophages (Kupffer Cells) in the Liver Sinusoids
• Macrophages of the Spleen and Bone Marrow
INFLAMMATION: ROLE OF NEUTROPHILS AND
MACROPHAGES
• INFLAMMATION
• When tissue injury occurs, by bacteria, trauma, chemicals, heat,
or any other phenomenon, multiple substances are released and
cause secondary changes in the surrounding uninjured tissues. This
complex of tissue changes is called inflammation.
• Vasodilation
• Increased permeability
• Clotting of the fluid
• Migration of granulocytes and monocytes
• Swelling of the tissue cells
“Walling-Off” Effect of Inflammation
• “Walling-Off” Effect of Inflammation

• “wall off” the area of injury from the remaining
tissues
• Tissue spaces and the lymphatics in the inflamed area
are blocked by fibrinogen clots
• Delays the spread of bacteria or toxic products
• Tissue Macrophages Provide a First Line of
Defense Against Infection
• Neutrophil Invasion of the Inflamed Area Is a Second
Line of Defense
• first hour after inflammation large numbers of neutrophils
begin to invade
• by inflammatory cytokines (e.g., tumor necrosis factor and
interleukin-1)
• cause increased expression of adhesion molecules, such as
selectins and intercellular adhesion molecule–1 (ICAM-1)
on the surface of endothelial cells in the capillaries and
venules
• reacting with complementary integrin molecules on the
neutrophils, cause the neutrophils to stick to the capillary
and venule walls in the inflamed area. This is called
margination
Migration of neutrophils from the blood into
inflamed tissue
Formation of Pus
• When neutrophils and macrophages engulf large numbers of

bacteria and necrotic tissue, a cavity is often excavated in the
inflamed tissues.
• This cavity contains varying portions of
• Necrotic tissue
• Dead neutrophils
• Dead macrophages
• Tissue fluid
• This mixture is commonly known as pus.
Philia and Penia
Absolute Neutrophil Count (ANC) Normal 4000–11,000 cells/mm3

• Neutrophilia 4000 to 5000 to 15,000 to 25,000
• Acute inflammation, so will be raised after a heart attack, other infarct or burns, malignancy
• Leukopenia <3700
• Aplastic anemia, hypersplenism, or overactive spleen, myelodysplastic syndromes,
myeloproliferative syndrome, myelofibrosis
• Neutropenia <1,500
• Chemotherapy, Hepatitis A,B,C, HIV/AIDS, Lyme disease, Malaria
• Eosinophilia >500
• parasitic infection, an allergic reaction or cancer
LEUKEMIAS
• Uncontrolled production of WBCs can be caused by

cancerous mutation of a myelogenous or lymphogenous
cell.
• This process causes leukemia, which is usually

characterized by greatly increased numbers of abnormal
WBCs in the circulating blood.

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Resistance of the Body to Infection

Leukocytes, Granulocytes, the

• Define the characteristics of Leukocytes

• Exposed continually to bacteria, viruses, fungi, and

• Special system for combating the infectious and

• Mobile units of the body’s protective system

• Types of White Blood Cells

• Myelocytic lineage, beginning with the myeloblast

• The most important function of the neutrophils and macrophages is

• The antibodies then adhere to the bacterial membranes and thereby

• “Walling-Off” Effect of Inflammation

• When neutrophils and macrophages engulf large numbers of

Absolute Neutrophil Count (ANC) Normal 4000–11,000 cells/mm3

• Uncontrolled production of WBCs can be caused by

• This process causes leukemia, which is usually

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