Lymphocyte Pathophysoiology

Lymphoblast

Lymphoblast

Prolymphocyte

mature lymphocyte

small lymphocyte

large, atypical lymphocytes

Plasma cells

What CD markers are associated with all stages of B cell maturity?

Mature B cells: CD45 (all lymph stages) and CD19-24
stem cells and early precursor B cells: CD34

CD markers associated with T-lymphs

CD45 (all lymphs), CD2,3,7 (all T-lymphs), CD4 and 8 determine functional group

What is the function of B cells?

- precursors for plasma cells
- synthesize and release ONE type of Ab (M/G in secondary lymphoid, A/E in mucosa)

What is the function of T-cells

- cellular immunity/modulators of humoral immunity
- interact with macrophages
- antigen directed response

Null lymphs (percentage/function)

10% of lymph population
represent: undifferentiated stem cell, immature T/B cell, lost surface receptors

Large Granular Lymphocytes (LGL)

- antibody dependent cytotoxicity
- NK (mediate cytotoxic rxns w/o prior sensitization) and K lymphs

Lymphocytopenia values

adult: <1.0 X 10^3/uL
child: <2.0 X 10^3/uL

What are causes of non-malignant lymphocytopenia?

- radiation
- acute stress
- cortisol
- chemotherapy
- AIDS
- Primary Immunodeficiency Disorders

X-linked Agammaglobulinemia (Bruton)

defects of B cells (mostly male babies), depleted B cell zones, recurrent infections

Hypogammaglobulinemia of infancy

B cell deficiency (delayed development/dec Igs), recurrent infection, self-correcting by 2 y/o

Late onset variable primary hypogammaglobulinemia

B cell deficiency (30 y/o), defect in differentiation of B cells into plasma cells, Inc infection and autoimmune disorders

Selective Immunoglobulin deficiency

acquired dec in 1 Ig subtype, IgA most common, associated with anaphylactic reactions

Thymic Aplasia (Di George's Syndrome)

defect of thymus gland, depleted T cell zones, normal serum Ig levels

Severe Combined Immunodeficiency Syndrome

inherited, T and B lymph deficiency, complete loss of humoral and cellular immunity

Lymphocytosis values

adults: > 4.0 X 10^3/uL
children: > 7.0 X 10^3/uL
infants: > 9.0 X 10^3/uL

What are the viral causes of infectious lymphocytosis?

Coxsackievirus A and B6, Echoviruses, Adenovirus

What symptoms/presentations are associated with viral infectious lymphocytosis?

vomiting, fever, abdominal discomfort, NO atypical lymphs, eosinophilia

Pertussis (whooping cough)

- bordetella pertussis
- lymphocytosis (small mature lymphs)
- LPF from pertussis organism

Infectious Mononucleosis (IM)

- EBV
- oral contact
- B cells have cell receptors specific for EBV, later T cells
- lymphocytosis, splenomegaly, lymphadenopathy (self-limit)

What are the complications associated with IM?

rash w/ ampicillin treatment, autoimmune hemolytic anemia, mild thrombocytopenia, jaundice/hepatitis, splenomegaly

Hematologic features of IM

- leukocytosis
- neutrophilia (metas, toxic granulation, Dohle body)
- abundant reactive lymphs

Serological findings for IM

heterophile Ab (absorbed by beef RBC), EBV-specific abs, autoimmune cold agglutinins (anti-i)

Cytomegalovirus (CMV)

- symptoms same as IM
- inc risk w/ transfusions and transplants
- close contact infection
- leukocytosis involving lymphocytosis

How would you differentiate CMV from IM?

- negative for heterophile Abs
- CMV abs
- cause congenital viral infections

Toxoplasmosis

- symptoms similar to IM
- Toxoplasma gondii
- absolute lymphocytosis and reactive lymphs
- = for heterophile/EBV Abs

How is toxoplasmosis diagnosed?

toxoplasmosis Abs (common host: house cat)

What are some other causes of lymphocytosis w/ reactive lymphs?

syphilis, smallpox, PAS hypersensitivity, phenytoin/mesentoin hypersensitivity

Hypergammaglobulinemia

levels of one or more serum Igs are increased above normal levels (may have abs. lymphocytosis)

Multiple Myeloma (MM)

- evolves from MGUS
- monoclonal gammopathy
- proliferation of plasma cells in BM

Symptoms of MM

- older and more men (2X more in AA pop.)
- bone pain/fractures
- increased calcium
- major cause of death: infection/renal failure

Multiple Myeloma lab profile

N/N anemia, rouleaux, inc ESR, hypervolemia/bleeding, BM: 1-90% plasma cells

What acronym goes with multiple myeloma's lab profile?

C- hyperCalcemia R-Renal insufficiency A-anemia B-bone lesions

What proteins are associated with MM (where do they show on electrophoresis?)

Bence Jones (gamma region M spike)

Multiple Myeloma treatment

melphalan-based high dose chemo (newer: angiogenesis inhibitors)

Waldenstrom's macroglobulinemia

- lymphoplasmacytic lymphoma (LPL) and BM involvement
- proliferation of B and plasma cells
- IgM inc in serum

What population has high prevalence of WM?

older white men

Symptoms of Waldenstrom's macroglobulinemia

cell proliferation/inc blood viscosity: nuero problems, renal insufficiency, heart failure, clotting probs
NO lytic bone lesions

WM lab profile

N/N anemia, thrombo/pancytopenia, lymphocytosis w/ normal WBC count, Rouleaux and inc ESR, IgM > 1, small normal lymphs and plasma cells in BM

WM treatment

chemo w/ alkylating agents, nucleoside analogues, and Rituximab

What are heavy chain diseases?

disorders related to production and excretion of the Ig heavy chains w/o light chains

Gamma Heavy Chain Disease

- > 50 y/o
- leukopenia, thrombocytopenia, atypical lymphs, plasma cells
- serum protein spike in beta-gama region (hypogamma)

Alpha Heavy Chain Disease

- more common (younger age group)
- intestinal involvement (malabsorption, diarrhea, infiltration in intestinal mucosa), lack of BM/lymph node involve
- normal protein electrophoresis

Mu Heavy Chain Disease

similar symptoms to Gamma-HCD