Chapter 33: Resistance of the Body to Infection: I. Leukocytes, Granulocytes, the Monocyte-Macrophage System, and Inflammation

Written By: Razaullah Khattak (DPT Medical Professional)

Student Source Reference: Guyton and Hall Textbook of Medical Physiology

Chapter: 33

To read more check out Chapter 16:

https://mednotesbyrazaullah.blogspot.com/2026/08/chapter-16-microcirculation-and.html

Leukocytes (White Blood Cells)

Leukocytes, commonly known as white blood cells, act as the mobile defense system of the human body. They originate partially in the bone marrow and partially in lymph tissues, using the bloodstream as a transport network to reach areas of infection and inflammation. Once at the target site, these specialized cells seek out, ingest, and destroy foreign invaders to protect tissue integrity.

Understanding leukocyte classifications, production pathways, life spans, phagocytic mechanisms, and inflammatory responses provides a foundation for immunology and pathology. When production is disrupted, life-threatening conditions like leukopenia or leukemia occur. This detailed breakdown organizes the fundamental principles of white blood cells based on core physiological concepts.

General Characteristics of Leukocytes

• Leukocytes act as mobile units defending the body.
• Cells form in bone marrow and lymph tissue.
• Blood transports leukocytes to infected body areas.
• Cells seek out and destroy foreign biological invaders.
• Six main white blood cell types exist normally.
• Neutrophils contain granular cytoplasm and multiple nuclei.
• Eosinophils display prominent cytoplasmic granules clinical terminology.
• Basophils function as granular polymorphonuclear leukocytes.
• Monocytes represent large agranular phagocytic blood cells.
• Lymphocytes mediate specific immune system responses.
• Plasma cells produce antigen-specific circulating antibodies.
• Megakaryocyte fragments form functional blood platelets.
• Granulocytes and monocytes ingest invaders via phagocytosis.
• Lymphocytes and plasma cells drive specific immunity.
• Platelets activate primary blood clotting mechanisms.
• Concentrations of White Blood Cells
• Adults average 7000 white cells per microliter.
• Red blood cells total 5 million per microliter.
• Neutrophils comprise 62 percent of total leukocytes.
• Eosinophils account for 2.3 percent of leukocytes.
• Basophils constitute 0.4 percent of circulating leukocytes.
• Monocytes represent 5.3 percent of white cells.
• Lymphocytes account for 30 percent of leukocytes.
• Platelet concentration averages 300,000 per microliter blood.

Genesis of White Blood Cells

• Hematopoietic stem cells yield two distinct lineages.
• Myelocytic lineage produces granulocytes and monocytes.
• Lymphocytic lineage produces lymphocytes and plasma cells.
• Bone marrow produces all human granulocytes.
• Bone marrow produces all circulating blood monocytes.
• Lymph glands produce lymphocytes and plasma cells.
• Spleen produces functional mature lymphocytic cells.
• Thymus generates differentiated T lymphocyte populations.
• Tonsils harbor functional producing lymphoid tissue.
• Peyer's patches generate lymphocytes underneath gut epithelium.
• Marrow stores three times circulating leukocyte numbers.
• Stored marrow leukocytes represent six-day supply.
• Lymphocytes reside stored inside tissue lymphoid organs.
• Megakaryocytes fragment inside marrow forming platelets.

Life Span of White Blood Cells

• Granulocytes circulate 4 to 8 hours normally.
• Granulocytes persist 4 to 5 days inside tissues.
• Severe infection shortens granulocyte life to hours.
• Monocytes circulate 10 to 20 hours in blood.
• Tissue macrophages live months performing defense duties.
• Lymphocytes circulate continuously between lymph and blood.
• Lymphocytes survive for weeks, months, or years.
• Platelets replace completely every ten days overall.
• Marrow produces 30,000 platelets daily per microliter.

Neutrophils and Macrophages Defense Capabilities

• Neutrophils and macrophages attack invading tissue bacteria.
• Blood neutrophils represent mature fully functional cells.
• Blood monocytes represent immature low-capability cells.
• Monocytes swell fivefold becoming active tissue macrophages.
• Macrophages reach sizes up to 80 micrometers.
• Cells enter tissues through narrow capillary pores.
• Squeezing process through capillary pores represents diapedesis.
• Cells move through tissues using ameboid motion.
• Ameboid velocities reach 40 micrometers per minute.
• Chemical signals attract leukocytes via positive chemotaxis.
• Inflamed tissues release chemical chemotactic products.
• Bacterial and viral toxins induce chemical chemotaxis.
• Degenerative tissue products trigger white cell migration.
• Complement complex products attract circulating phagocytic cells.
• Plasma clotting products generate chemotactic gradient signals.
• Chemotaxis operates effectively up to 100 micrometers.

Mechanisms of Phagocytosis

• Phagocytosis means cellular ingestion of foreign material.
• Phagocytes select targets avoiding normal body structures.
• Smooth cellular surfaces resist natural phagocytic ingestion.
• Protective protein coats repel active tissue phagocytes.
• Dead tissue lacks protective protein surface coats.
• Antibodies adhere directly to target bacterial membranes.
• Antibodies combine with C3 complement reaction products.
• Complement C3 attaches phagocyte surface membrane receptors.
• Opsonization describes target selection and phagocytosis initiation.
• Neutrophils project surrounding pseudopodia around foreign targets.
• Fused pseudopodia isolate chamber forming intracellular phagosome.
• Single neutrophils ingest 3 to 20 bacteria.
• Activated macrophages phagocytize up to 100 bacteria.
• Macrophages engulf large structures including whole RBCs.
• Macrophages extrude digest residual products surviving months.

Intracellular Digestion and Bacterial Killing

• Lysosomes fuse directly with internal phagocytic vesicles.
• Digestive enzymes enter newly formed phagocytic vesicles.
• Proteolytic enzymes fill neutrophil and macrophage lysosomes.
• Macrophage lysosomes contain specialized lipid-digesting lipases.
• Peroxisomes form powerful biological cellular oxidizing agents.
• Superoxide ions kill ingested live bacterial organisms.
• Hydrogen peroxide acts as powerful bactericidal agent.
• Hydroxyl ions destroy target biological cell structures.
• Myeloperoxidase catalyzes hypochlorite production from peroxide.
• Tuberculosis bacilli possess enzyme-resistant protective coats.

Monocyte-Macrophage System (Reticuloendothelial System)

• Fixed macrophages attach tissues surviving months or years.
• Stimulated fixed macrophages detach becoming mobile again.
• Monocyte-macrophage system spans all body tissues.
• Reticuloendothelial system includes monocytes and tissue macrophages.
• Subcutaneous histiocytes divide locally attacking skin infections.
• Lymph nodes trap entering foreign particulate matter.
• Afferent lymphatics deliver lymph into nodal sinuses.
• Sinus macrophages phagocytize entering foreign lymph particles.
• Efferent lymphatics carry cleared lymph toward veins.
• Alveolar macrophages line pulmonary alveolar internal walls.
• Alveolar macrophages digest or encase non-digestible particles.
• Macrophages form giant cell capsules around tuberculosis.
• Gastrointestinal bacteria enter portal circulation continuously.
• Kupffer cells line hepatic tissue blood sinusoids.
• Kupffer cells engulf single bacteria within milliseconds.
• Splenic red pulp trabeculae contain dense macrophages.
• Splenic macrophages clean blood and remove aged red cells.

Inflammatory Process and Tissue Response

• Injured tissues release secondary signal reaction products.
• Local blood vessels dilate increasing regional flow.
• Capillary permeability increases leaking protein rich fluid.
• Interstitial fibrinogen leaks forming local tissue clots.
• Large numbers of leukocytes migrate into inflamed tissues.
• Inflamed local tissue cells swell significantly overall.
• Histamine and bradykinin in initiate local inflammatory vascular changes.
• Serotonin and prostaglandins trigger regional inflammatory responses.
• Activated macrophages begin devouring destroyed local tissues.
• Fibrinogen clots wall off injured local tissue spaces.
• Walling-off delays systemic spread of toxic bacterial products.
• Staphylococci trigger intense rapid local walling-off reactions.
• Streptococci trigger slow walling-off allowing systemic spread.

Lines of Defense During Inflammation

• Tissue macrophages represent immediate first line defense.
• Sessile macrophages enlarge and break loose immediately.
• Neutrophils invade inflamed areas as second defense line.
• Inflammatory cytokines in TNF and IL-1 activate endothelium.
• Selectins and ICAM-1 increase on capillary walls.
• Neutrophils stick to activated endothelium via margination.
• Intercellular endothelial attachments loosen permitting diapedesis.
• Neutrophils migrate directly toward damaged tissue spaces.
• Inflammatory products mobilize stored marrow neutrophils.
• Neutrophilia increases blood neutrophils four to fivefold.
• Blood monocytes enter tissue as third line defense.
• Monocytes require 8 hours swelling into macrophages.
• Macrophages dominate inflamed tissue after several days.
• Marrow increases leukocyte production as fourth defense line.
• Marrow increases cell production 20 to 50 fold.

Feedback Control and Pus Formation

• Activated macrophages release five dominant growth factors.
• TNF and IL-1 drive local inflammatory feedback.
• GM-CSF stimulates marrow granulocyte and monocyte production.
• G-CSF specifically stimulates bone marrow granulocyte production.
• M-CSF selectively stimulates marrow monocyte cell line.
• Dying neutrophils and macrophages form internal cavities.
• Mixture of dead cells and fluid forms pus.
• Suppressed infection allows cell autolysis and absorption.

Eosinophils and Basophils Physiology

• Eosinophils constitute 2 percent of total leukocytes.
• Eosinophils exhibit weak phagocytosis against common infections.
• Eosinophils attack large human parasitic tissue infections.
• Cells attach parasites releasing hydrolytic lysosomal enzymes.
• Eosinophils release lethal reactive forms of oxygen.
• Major basic protein acts as powerful larvacidal polypeptide.
• Eosinophils migrate toward allergic tissues via chemotaxis.
• Mast cells release eosinophil chemotactic factor during allergies.
• Eosinophils detoxify allergy substances and allergen-antibody complexes.
• Basophils and mast cells liberate anticoagulant heparin.
• Mast cells release histamine, bradykinin, and serotonin.
• IgE antibodies bind basophil and mast cell membranes.
• Antigen-antibody binding ruptures cells releasing allergic mediators.

Leukopenia and Leukemia Pathology

• Leukopenia means marrow produces very few leukocytes.
• Loss of leukocytes allows immediate local bacterial invasion.
• Mouth and colon ulcers appear within two days.
• Untreated total leukopenia causes death within one week.
• Radiation and benzene nuclear drugs cause bone marrow aplasia.
• Chloramphenicol and barbiturates rarely induce severe leukopenia.
• Transfusions and antibiotics support marrow stem cell regeneration.
• Leukemia means uncontrolled cancerous white cell production.
• Lymphocytic leukemias begin inside tissue lymph nodes.
• Myelogenous leukemias begin within bone marrow stem cells.
• Undifferentiated leukemic cells cause acute rapid death.
• Differentiated leukemic cells cause chronic long-term disease.
• Leukemic cell metastasis invades bones causing pain.
• Leukemia causes infection, severe anemia, and thrombocytopenia.
• Cancerous cells consume excessive metabolic amino acids and energy.
• Rapid protein depletion causes eventual lethal patient starvation.

Disclaimer: This content is for educational purposes only and not a substitute for professional medical advice.