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MLAB 1415- Hematology Keri Brophy-Martinez. Chapter 20: Nonmalignant Lymphocyte Disorders. Review. Lymphs originate primarily from bone marrow and thymus Secondary organs include spleen, lymph nodes, tonsils, and Peyer’s patches in GI tract. Review. 3 general populations B- lymphs: 10-20 %
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MLAB 1415- HematologyKeri Brophy-Martinez Chapter 20: Nonmalignant Lymphocyte Disorders
Review • Lymphs originate primarily from bone marrow and thymus • Secondary organs include spleen, lymph nodes, tonsils, and Peyer’s patches in GI tract
Review • 3 general populations • B- lymphs: 10-20 % • T-lymphs: 60-80% • NK: < 10% Pluripotent Stem cell Lymphocyte Stem cell B-cell T-cell
Characteristic Cell • Reactive lymphocyte - transformed or benign lymph • Familiar terms are immunocytes, transformed lymph, immunoblast, plasmacytoid, Downey cell • Why causes them? • Virus attaches to the B- lymphocyte and infects it • This binding “activates” the lymphocyte causing it to express an activation marker (CD23) • CD23 is the receptor for the B-lymph growth factor • Once the virus is inside the cell, it incorporates itself into the B-cell genome to make more viral proteins, and keep passing itself on to future B-lymphs
Introduction • Majority of disorders affecting lymphocytes are acquired • Hallmark: reactive lymphocytosis • Reactive process • Congenital disorders • Defect is found within lymphocytic system
Introduction • Important to differenciate benign conditions associated with lymphocytosis from malignant lymphoproliferative disorders • How? • Presence of reactive lymphs • Positive serological test for antibodies against infectious organisms • Absence of anemia and thrombocytopenia • All of above favor a benign diagnosis
Lymphocytosis • Excess of lymphocytes in the blood. • Absolute lymphocyte count (ALC) > 4.8 x 109 /L in adults • Relative count > 35-45% • Self-limited • Reactive process is due to infection or inflammatory conditions • B and T cells involved • Lymphocytes develop in response to antigenic stimulation. They become “activated”
Causes of Reactive Lymphocytosis • Infectious mononucleosis (IM) • Caused by the Epstein-Barr Virus (EBV) which enters the body via saliva (“kissing disease”) • Clinical symptoms • Classic triad: fever, pharyngitis and lymphadenpathy • Dysphagia • General malaise • Fatigue • Spleen is enlarged and nodes are firm but not tender or warm • Generally seen in children and young adults (17-25 yrs old)
Lab features of IM • CBC • Relative lymphocytosis • Peaks at 2-3 weeks of infection, remains elevated for 2-8 weeks • Leukocyte count 12-25 x 109/L • Peripheral smear • Typical lymphocyte is historically referred to as a Downey cell with irregular cytoplasmic border, increased cytoplasm and dark blue edge around the periphery of the cytoplasm. • >20% reactive lymphs • Serologic test • Heterophil antibody test (i.eMonospot)
Causes of Reactive Lymphocytosis • Toxoplasmosis • Infection with intracellular protozoan Toxoplasma gondii • Acquired infections in children and adults due to ingestion of oocysts from cat feces or undercooked meat • Can be transmitted via placenta
Causes of Reactive Lymphocytosis • Cytomegalovirus (CMV) Infection • Belongs to herpes family • Endemic worldwide • Acquired through transfusions, sexual contact and close contact • Can be transmitted across placenta • Poor prognosis for immunocompromised individuals who contract virus
Causes of Reactive Lymphocytosis • Infectious lymphocytosis • Affects children • Viruses include adenovirus, coxsackie A and Bordetella pertussis • Leukocytosis and lymphocytosis occur in first week of illness then return to normal
Lymphocytopenia • Absolute lymphocyte count< 1.0 x 109/L • Causes • Decreased production or increased destruction of lymphocytes • Changes in lymphocyte circulation patterns • Other unknown causes • Refer to page 411, table 20-4
Immune Deficiency Disorders • Impaired function of one or more of the components of the immune system: T, B, or NK lymphocytes • Body unable to mount an adaptive immune response • Can be acquired or congenital
Acquired Deficiencies • Acquired immune deficiency syndrome (AIDS) • Infection with a retrovirus, human immunodeficiency virus type-1 (HIV-1) • Transmission through sexual contact or contact with blood and/or blood products
Congenital Deficiencies • Decrease in lymphocytes and impairment in either cell-mediated immunity (Tcells), humoral immunity(Bcells) or both • Lymphocytes appear normal on ps
Congenital Deficiencies • Severe Combined immunodeficiency Syndrome • Major qualitative immune defects involving both humoral and cellular immune functions • Wiskott-Aldrich Syndrome • Patients have recurrent infections due to immunodeficiency, thrombocytopenia and eczema