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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 % 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 Cell Characterisitcs Reactive Lymph Normal Lymph 9-30 µm 8-12 µm Cytoplasm Abundant Colorless to dark blue Azurophilic granules Can scallop the RBCs Scant Colorless to light blue Nucleus Elongated, irregular Round Chromatin Coarse to moderately fine Coarse Nucleoli Absent to distinct Absent Size N:C ratio 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.e Monospot) 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