1. MLAB 1415- Hematology Keri Brophy-Martinez
Chapter 20:
Nonmalignant Lymphocyte Disorders

2. Review Lymphs originate primarily from bone marrow and thymus
Secondary organs include spleen, lymph nodes, tonsils, and Peyer’s patches in GI tract

3. Review Pluripotent Stem cell Lymphocyte Stem cell B-cell T-cell
3 general populations
B- lymphs: %
T-lymphs: 60-80%
NK: < 10%

4. 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

5. Cell Characterisitcs Reactive Lymph Normal Lymph Size 9-30 µm 8-12 µm
N:C ratio
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

6. Introduction Majority of disorders affecting lymphocytes are acquired
Hallmark: reactive lymphocytosis
Reactive process
Congenital disorders
Defect is found within lymphocytic system

7. 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

8. 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”

9. 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)

10. Lab features of IM CBC Relative lymphocytosis
Peaks at 2-3 weeks of infection, remains elevated for 2-8 weeks
Leukocyte count 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)

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. Congenital Deficiencies
Decrease in lymphocytes and impairment in either cell-mediated immunity (Tcells), humoral immunity(Bcells) or both
Lymphocytes appear normal on ps

18. 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