White Blood Cell Functions and Hematopoiesis

Alterations in White Blood Cells

• White blood cells (WBCs) are crucial for defending against disease, primarily operating outside the bloodstream.
• WBCs exhibit key functions including margination, rolling, adhesion, transmigration (diapedesis), and chemotaxis.

Hematopoiesis

• Hematopoiesis is the process of blood cell formation.
• The process begins with a pluripotent stem cell, which differentiates into myeloid and lymphoid stem cells.
• Myeloid stem cells generate granulocytes, megakaryocytes, and erythrocytes.
• Lymphoid stem cells generate B cells and T cells which mature into plasma cells and various T-cells.
• Common Fate Unit (CFU) cells are intermediates in the development process

Functions of WBCs

• WBCs primarily function to protect against disease.
• They actively work outside the bloodstream.
• WBCs participate in key processes like margination, rolling, and adhesion, and transmigration.
• WBCs use chemotaxis to navigate toward infection sites.
• Phagocytosis involves recognition, engulfment, killing, and digestion of pathogens by neutrophils and monocytes (active phagocytes)

Lysosomal Constituents

• Lysosomes contain enzymes for breaking down foreign particles.
• Primary lysosomes (azurophilic, non-specific) contain myeloperoxidase, lysozyme (bacteria targeted), and acid hydrolases.
• Secondary lysosomes (specific) contain lactoferrin, lysozyme (again bacteria), alkaline phosphatase, and collagenase.

Benign Disorders of White Blood Cells

• Benign white blood cell disorders can be categorized as either qualitative (morphological or functional changes) or quantitative (changes in number).

Quantitative Disorders of White Blood Cells

• Leukocytosis involves an increased number of white blood cells.
• The normal range of leukocytes in peripheral blood is 4000 to 11,000/μL.
• Leukopenia describes a reduced number of white blood cells.
• Specific types of leukopenia include neutropenia (low neutrophils) and lymphopenia (low lymphocytes).
• Related terms include leukocytosis, neutrophilia, eosinophilia, basophilia, lymphocytosis, monocytosis and their respective decreased counterparts.

Neutropenia

• Neutropenia is specifically a reduced neutrophil count (less than 1500 cells/μL).
• Agranulocytosis denotes severe neutropenia (neutrophil count less than 200 cells/μL).
• Neutropenia has congenital (e.g., Kostmann's syndrome) and acquired causes (e.g., accelerated removal, increased destruction, drug-induced granulocytopenia, irradiation, autoimmune disorders, splenomegaly).
• Acquired neutropenia includes various conditions like Felty's syndrome, neoplasms, alcoholism, and nutritional deficiencies (folate, vitamin B12, iron, copper).
• Aplastic anemia and idiopathic neutropenia are also included.

Neutrophilia

• Physiological causes include newborns, pregnancy, labor, postpartum, and post-exercise.
• Drug-induced neutrophilia can be caused by corticosteroids.
• Other causes include acute poisoning with heavy metals (Hg) and some venoms.
• Reactive neutrophilia results from increased neutrophil release from bone marrow to accommodate high tissue affinity, often accompanied by leukocyte formula deviation ("leukemoid reaction").
• Metabolic and endocrine diseases (diabetic ketoacidosis, acute renal failure, acute gout) and some malignant hematologic diseases (CGL, PV, CMML) are also potential causes

Eosinophilia

• Eosinophilia is an increased blood eosinophil count.
• Potential causes include allergic diseases (asthma, allergic rhinitis, eczema, atopic dermatitis), parasitic infections, fungal and other infections, tuberculosis, and hematologic and non-hematologic malignancies.

Lymphocytosis

• Lymphocytosis is an elevated lymphocyte count.
• Absolute lymphocytosis has causes like acute viral infections (infectious mononucleosis, hepatitis, cytomegalovirus), other acute infections (pertussis), protozoal infections (toxoplasmosis), and chronic intracellular bacterial infections (tuberculosis, brucellosis), and chronic lymphocytic leukemia.
• Relative lymphocytosis causes include age less than two years, acute viral infections, connective tissue diseases, splenomegaly with splenic sequestration of granulocytes, exercise, and stress.
• Infectious mononucleosis, caused by Epstein-Barr virus, is characterized by virus infection of epithelial and B cells; saliva from infected persons is the chief mode of transmission. The condition often does not cause illness in children below age 10 and confers lifelong immunity afterward.

Monocytosis

• Monocytosis is an elevated level of monocytes.
• Chronic inflammation, infections (tuberculosis, brucellosis), autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis), malignancies (Hodgkin's disease, certain leukemias), and recovery from neutropenia or acute infections are frequent causes.

Monocytopenia

• Monocytopenia is characterized by low monocyte levels.
• Potential causes include acute infections, stress, aplastic anemia, hairy cell leukemia, acute myeloid leukemia, treatment with myelotoxic drugs, and treatment with glucocorticoids.

Basophilia

• Basophilia, an increased basophil count, could result from a surgery complication (e.g., splenectomy), infectious disorders (Influenza, Chickenpox), infected organ sites (abscesses), inflammatory disorders, and neoplastic disorders (acute myeloid leukemia, Hodgkin's disease).
• Further causes of basophilia include allergic/collagen autoimmune disorders, congenital/developmental disorders, hereditary/familial/genetic disorders (e.g., spherocytosis), vegetative/autonomic/endocrine disorders (e.g., hypothyroidism), a leukemoid reaction, drug reactions, and foreign protein injection.

Qualitative Disorders of White Blood Cells

• Qualitative disorders involve changes in the form or function of white blood cells.
• Pelger-Huet anomaly is an inherited genetic mutation (sometimes acquired) causing abnormal neutrophil shapes (bilobed, peanut, or dumbbell).
• Chediak-Higashi syndrome (genetic disorder) presents with abnormal large irregular granules, impaired lysosomal digestion of bacteria, and association with pigment disorders and blood disorders.
• These abnormalities are usually associated with an increased risk of infection.

Chronic Granulomatous Disease (CGD)

• In Chronic granulomatous disease (CGD), abnormal neutrophils phagocytose microorganisms but cannot kill them due to a lack of respiratory burst and peroxidase production.

Leukocyte Adhesion Deficiency (LAD)

• Leukocyte adhesion deficiency (LAD) is an autosomal recessive disorder impacting leukocyte cell-surface adhesion proteins (integrins), specifically the CD11/CD18 complex.
• Defective adhesion to endothelial cells, chemotaxis, C3bi-mediated phagocytosis, particle-triggered respiratory burst activation, and degranulation are characteristic of this condition.
• Common clinical features include frequent bacterial and fungal infections, lack of pus formation, and delayed umbilical cord separation, along with persistent leukocytosis. Diagnosis involves flow cytometry analysis of neutrophil CD11/CD18 levels.