Module 2: Normal Leukocytes Flashcards
Define leukopoiesis
Production of leukocytes
Where are leukocytes produced?
Bone marrow (neutrophils, monocytes, eosinophils, basophils, and a few lymphocytes) Lymphatic tissue (lymphocytes and plasma cells)
How is leukocyte production similar to erythrocyte production?
Mitosis and differentiation of a stem cell
Immature cell replicates itself and then transforms into a more mature form by undergoing physical and chemical changes induced by leukopoietins
What are leukopoietins?
Hormones and cytokinds that alone or in synergy induce growth and/or differentiation in leukocyte stem or blast cells
Name 4 leukopoietins
IL-1 to IL-19
GM-CSF
G-CSF
M-CSF
What is the major function of leukocytes?
Protection against foreign and malignant cells and molecules
How do leukocytes remove foreign bodies?
- Phagocytosis of foreign antigen that is labelled by antibodies
- Lysis of foreign and infected cells by direct killing mechanisms
What are the 6 main functions of the immune system?
- Encounters
- Recognition
- Activation
- Deployment
- Discrimination
- Regulation
What occurs in the encounter stage of the immune system?
Foreign bodies are encountered by recognition cells (lymphocytes and macrophages) by
- Lymphatic circulation bringing antigens and cells through the lymph nodes where lymphocytes and macrophages are
- Patrolling lymphocytes and macrophages in the blood, lymph, and extracellular fluid
What happens in the recognition stage of the immune system?
There are antigen specific receptors on the surface of lymphocytes that recognize the antigen and produce specific antibodies
What happens in the activation stage of the immune system?
After an antigen is recognized as foreign the lymphocytes are activated and produce antibodies or chemical mediators to direct activities of other cells
What happens in the deployment stage of the immune system?
Activated lymphocytes amplify and distribute defense products and collaborate with phagocytes and complement to destroy the antigen
What happens in the discrimination stage of the immune system?
Discrimination between self and non-self avoids autoimmune tissue damage
What happens in the regulation stage of the immune system?
Regulation of the response intensity ensures an appropriate size reaction takes place and shuts off when the antigen is eliminated
What do lymphocytes do?
Responsible for detection and recognition of foreign and abnormal self-antigens and initiating specific responses
Cytolytic killing, production of antibodies and lymphokines, and facilitating phagocytes
What are the 3 types of lymphocytes?
B lymphocyte
T lymphocyte
Null cells
What do B lymphocytes do?
Humoral immune responses by transformation into plasma cells
What do T lymphocytes do?
Cellular immune response, involved in regulation of antibody reactions by helping or suppressing B lymphocyte activation
What are the 2 types of Null cells? What does each one do?
Killer cells - antibody dependent cell-mediated lysis
Natural killer cells - direct cytotoxic activity
What are 4 things that make lymphocytes different from other leukocytes?
- Resting cells, get stimulated to undergo mitosis and produce memory and effector cells
- Circulate from blood to tissues and back
- B and T cells rearrange antigen receptor gene segments to produce a variety of antibodies and surface receptors
- T and null cells develop and mature outside the bone marrow
Where do lymphocytes mature in utero and after birth?
In the embryonic stage they develop from the pluripotent cells of the yolk sac and liver
Fetuses and adults have stem cells that differentiate to CFU-L stem cells in the bone marrow which are stimulated and then mature in the lymphatic tissue
What are primary and secondary lymphoid tissues?
Primary - bone marrow and thymus
Secondary - lymph nodes, spleen, tonsils, Peyer’s patches, etc
How do lymphocytes develop in primary tissue?
Lymphocytes are produced and differentiated without antigenic stimulation
Thymus cells become T lymphocytes, bone marrow cells become B lymphocytes
How do lymphocytes develop in secondary tissue?
Depends on antigenic stimulation
Secondary lymphoid tissue acts as a storage area for already differentiated lymphocytes
What cytokines stimulate lymphocytic differentiation from stem cells?
IL-1 and IL-6
Describe the morphology of a lymphoblast
15-20um
4:1 N/C ratio
Round/oval finely clumpped nucleus with 1-2 nucleoli
Small medium blue cytoplasm with no granules, possibly dark border
Describe the morphology of a prolymphocyte
15-18um
4:1 to 3:1 N/C ratio
Oval/slightly indented slightly clumped nucleus with 0-1 nucleoli
Small medium blue cytoplasm, possible azuorphilic granules, dark rim
Describe the morphology of a lymphocyte
6-9um (small) 17-20um (large)
4:1-3:1 N/C ratio (small) 2:1 N/C ratio (large)
Round/oval/indented dense nucleus with no nucleoli
Scant light blue cytoplasm with possible azuorphilic granules
What is the common CD marker that a lymphoblast would have?
CD34
TdT
What are common CD markers that B lymphocytes would have?
CD10 - precursors CD19 - precursor and mature CD20 - activation CD22 - activation (cytoplasmic) CD38 & CD138 - plasma cells
What are common CD markers that T lymphocytes would have?
CD2 - early CD3 - Pan-T cell CD4 - T cell subset CD5 CD7 - early CD8 CD56 - T cell subset
What percentage of lymphocytes are found in the peripheral blood?
20-40% in adults (60-80% T, 20-35% B)
Higher in children up to age 4
How can small and large lymphocytes be distinguished morphologically?
Small - darker and denser nucleus usually no nucleoli, scant to moderate usually darker cytoplasm rarely have granules
Large - lighter less clumped nucleus may be stretched and contain nucleoli, more abundant lighter cytoplasm may contain azurophilic granules
What is a variant lymphocyte?
A stimulated lymphocyte, increased DNA and RNA activity
Normal, immune system function
What do variant lymphocytes look like?
Larger
Possible folded/indented/lobulated nucleus with varying chromatin clumping, often 1-3 nucleoli
Cytoplasm may be gray to deep blue, foamy/vacuolated, usually abundant with uneven staining, may have granules
How many variant lymphocytes in the peripheral blood are normal?
5-6% of lymphocytes
Increased in viral disorders (mono, etc)
How many neutrophils are usually present in the blood?
50-70%
Most numerous in blood and bone marrow
How long does a neutrophil live in different areas of the body?
Blast > Promyelocte > Myleocyte - 1 day
Metamyelocyte > Band > Neutrophil - 6-10 days
In the blood - 10 hours
In the tissue - 3-5 days
Describe the morphology of a myeloblast
15-20um
7:1-5:1 N/C ratio
Round/oval, central/eccentric fine nucleus, 1-3 nucleoli
Scant basophilic cytoplasm, no granules
Describe the morphology of a promyelocyte
12-24um
5:1-3:1 N/C ratio
Round/oval, central/eccentric slightly clumped nucleus, 1-2 nucleoli
Basophilic cytoplasm, azurophilic and non-specific granules
Describe the morphology of a myelocyte
10-18um
2:1-1:1 N/C ratio
Oval/round/slightly indented eccentric slightly more clumped nucleus, 0-2 nucleoli
Bluish-pink moderate cytoplasm, azurophilic and specific granules
Describe the morphology of a metamyelocyte
10-18um
1:1 N/C ratio
Indented kidney shaped central/eccentric clumped nucleus, 0 nucleoli
Clear pink moderate cytoplasm, specific granules
Describe the morphology of a band
10-16um
1:1-1:2 N/C ratio
Elongated horseshoe central/eccentric clumped nucleus, 0 nucleoli
Pink abundant cytoplasm, fine violet-pink granules
Describe the morphology of a neutrophil
10-16um
1:3 N/C ratio
2-5 clumped lobes, 0 nucleoli
Pink abundant cytoplasm, violet-pink granules
What is present in primary and secondary granules?
Primary - lysozyme, myleoperoxidase, acid phosphatase, elastase
Secondary - lysozyme, NADPH oxidase, cytochrome b, lactoferrin
What are tertiary granules (seen through electron microscopy)
Plasminogen activator, alkaline phosphatase, and gelatinase
What receptors do neutrophils have on their membranes?
Fc portion of IgG
C3b and C5a complement components
Insulin and histamine (not important in immune system)
What is present on the outside of a neutrophil and what does it do?
Glycoprotein coating to allow adherance
Actin, myosin, and tubulin to allow migration and phagocytosis
What is the function of a neutrophil?
Locate and destroy foreign antigens through phagocytosis
What is the neutrophil migration sequence?
How neutrophils migrate from the blood to the site of an infection
Includes: margination, adherence, anchoring, diapedesis and migration
What is margination?
50% of neutrophils roll along the inside of blood vessels instead of circulating
What is adherence?
Neutrophils flatten against the endothelium of the vessel
Endothelial cells become more adherent near inflammation due to chemical mediators
What is anchoring?
Permanent adherence of neutrophils to the endothelial cells due to large amounts of chemical mediators
What is diapedesis?
Neutrophils moving through junctions between endothelial cells to reach the infection
Aided by vasodilators from the infected site and proteases secreted by the neutrophil to digest the basement membrane