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LYMPHOCYTES

• Lymphocyte precursors develop from the pluripotential hematopoietic stem cell in the bone marrow.
• They differentiate into several functionally different types of lymphocytes (T, B, NK cells), all of which are involved in an immune response.
• Lymphocyte Size: Large 11-16 μm, small 7-10 μm
• Count: Newborn: 25-35% (2-11 x 10^9μ/l) Children: 50-65% (2-8 x 10^9μ/l) Adult 25-35% (2-4 x 10^9μ/l)

LYMPHOCYTOSIS

• Clinical condition in which the absolute lymphocyte count exceeds more than 4.0×10^9/μl in adults and 9.0×10^9/μ in children is known as lymphocytosis or lymphoproliferative disorders.
• Lymphocytosis is usually a self-limiting, reactive process that occurs in response to an infection or inflammatory condition.
• Both T and B lymphocytes are commonly affected, but their function remains normal.
• Occasionally, viral infections can cause functional impairment of the lymphocytes, yielding both a qualitative disorder and quantitative changes.
• T lymphocytes normally compose about 60–80% of peripheral blood lymphocytes.
• Absolute lymphocytosis is not usually accompanied by leukocytosis except in infectious mononucleosis, Bordetella pertussis infection, cytomegalovirus infection, and lymphocytic leukemia.
• A relative lymphocytosis is secondary to neutropenia that occurs in a variety of viral infections is more commonly found.

CAUSES OF LYMPHOCYTOSIS

  1. Infectious mononucleosis
    • It is a self-limiting lymphoproliferative disease caused by Epstein-Barr virus (EBV).
    • It usually affects young adults; the peak age for infection is 14–24 years.
    • EBV attaches to a receptor on the B lymphocyte membrane (CD21) which is the receptor for the C3d complement component.
    • The infection first occurs in the oropharynx and then spreads to the blood, where it infects B lymphocytes and epithelial cells of the pharynx, resulting in the prominent sore throat.
    • A complex, multifaceted cellular immune response controls acute EBV infection.
    • In the first week of illness, an increase polyclonal immunoglobulins occurs.
    • During the second week, however, the number of immunoglobulin-secreting B lymphocytes decreases because of the action of CD8+ T lymphocytes and NK cells.
    • The majority of the reactive lymphocytes seen in the peripheral blood are these CD8+ cytotoxic T lymphocytes.

Infectious mononucleosis lab findings:
• Early symptoms include lethargy, headache, fever, chills, sore throat, nausea, and anoxia.
• The classic triad presentation of symptoms are fever, pharyngitis, and lymphadenopathy
• The cervical, axillary, and inguinal lymph nodes are commonly enlarged.
• Splenomegaly occurs in 50–75% of these patients, and hepatomegaly occurs in about 25% cases.
• Occasionally, jaundice, autoimmune hemolytic anemia, thrombocytopenia, agranulocytosis, and aplastic anemia rarely developed.
• The disease is usually self-limiting, resolving within a few weeks.

• Peripheral blood film reveals leukocytosis(12- 25×10^9/μl) due to absolute lymphocytosis.
• Lymphocytes usually constitute >50% of the leukocytes >20% reactive lymphocytes.
• The platelet count is often mildly decreased; concentrations of <100 x 10^9/μl are rare.
• Immunoblasts are usually present early in the disease. Plasmacytoid lymphocytes and an occasional plasma cell also can be found.
• Bone marrow aspiration shows hyper cellular marrow of all cells except neutrophils.
• Solid phase immunoassay tests is positive for heterophil antibodies.
• VCA-IgM &IgG,EBV nuclear antigens (EBNA) immunoassay also performed for diagnosis
• Confirmatory diagnosis is done EBV by PCR method.

2. Toxoplasmosis:
• Toxoplasmosis is the result of infection with the intracellular protozoan Toxoplasma gondii.
• This obligate intracellular parasite can multiply in all body cells except erythrocytes.
• Infections are often asymptomatic but carriage a significant risk to the fetus of a pregnant woman.
• Transplacental infection can cause abortion, jaundice, hepatosplenomegaly, chorioretinitis, hydrocephalus, microcephaly, cerebral calcification, and mental retardation.
• Peripheral blood film shows leukocytosis with a relative lymphocytosis or (more rarely) an absolute lymphocytosis with reactive lymphocytes morphologically similar to lymphoblasts or lymphoma cells.
• The heterophile antibody test is negative.
• Biopsy of lymph nodes shows a reactive follicular hyperplasia and can play an important role in diagnosis.
• Diagnosis of an active infection is confirmed by seroconversion and arising titer of antibodies to T. gondii.

3. Cytomegalovirus (CMV):
• It can cause congenital or acquired infections in neonates when CMV infected pregnant woman crosses the placenta and infects the fetus.
• The newborn present with jaundice, microcephaly, and hepatosplenomegaly.
• Only about 10% of infected infants exhibit clinical evidence of the disease.
• The most common hematologic findings in neonates are thrombocytopenia and hemolytic anemia.

• It can cause congenital or acquired infections in neonates when CMV infected pregnant woman crosses the placenta and infects the fetus.
• The newborn present with jaundice, microcephaly, and hepatosplenomegaly.
• Only about 10% of infected infants exhibit clinical evidence of the disease.
• The most common hematologic findings in neonates are thrombocytopenia and hemolytic anemia.

• Acquired infection is spread by close contact, blood transfusions, and sexual contact.
• It is common in immunosuppressed individuals, patient with malignancy due to massive blood transfusions
• It is the most common viral infection complicating tissue transplants.
• Infected adults present with symptoms similar to those of infectious mononucleosis except that pharyngitis is absent.

• Laboratory findings include a leukocytosis with an absolute lymphocytosis with reactive lymphocytes and heterophile antibody test is negative.
• Hepatic enzymes are usually abnormal.
• Diagnosis is confirmed by demonstrating the virus in the urine or blood using a viral DNA (molecular) assay or by a rise in the cytomegalovirus antibody titer

4. Bordetella pertussis:
• Bordetella pertussis causing whooping cough.
• Blood picture is very similar to that of reactive viral lymphocytosis.
• Total leukocyte count increased up to 15- 50×10^9/μl with absolute lymphocytosis of T, B, and natural killer (NK).
• lymphocytes along with increases in neutrophils, monocytes and granulocytes shows toxic changes.
• Virus culture, serology and PCR diagnostic tests

5. Persistent Polyclonal B-Cell Lymphocytosis:
• It is a rare disorder found primarily in the female adult smoker and consist of polyclonal expression of lymphocytes.
• Mostly it is HLA-DR7 haplotype, partial insertion of chromosome 3, i(3q), and multiple IgH/Bcl-2 rearrangements that suggest PPBL could lead to a malignant process.
• Clinically it is asymptomatic and some time it present with symptoms such as fever, fatigue, weight loss, recurrent chest infections or generalized lymphadenopathy.
• Laboratory findings shows lymphocytosis and the presence of binucleated lymphocytes.
• There is a polyclonal increase in serum IgM but low IgG and IgA levels.
• Bone marrow examination reveals lymphocytic infiltrates.

LYMPHOCYTOPENIA

• Clinical condition in which the absolute lymphocyte count is less than 1.0 x 10^9/μl.
• Lymphocytopenia results from decreased production or increased destruction, changes in lymphocyte circulation patterns and other unknown causes.
• Corticosteroid therapy causes a sharp drop in circulating lymphocytes within 4 hours.
• The decrease is caused by sequestration of lymphocytes in the bone marrow

• Malnutrition
• Disseminated neoplasms
• Connective tissue disease (e.g., systemic lupus erythematosus)
• Hodgkin’s disease
• Chemotherapy
• Radiotherapy
• Corticosteroids
• Acute inflammatory conditions
• Chronic infection (e.g., tuberculosis)
• Congenital immune deficiency diseases
• Acquired immune deficiency diseases
• Acute and chronic renal disease
• Stress

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