hema 1 -MT113- MODULE 4 HEMATOPOIESIS (LYMPHOID AND MONOCYTIC SERIES)

Lymphocytes and plasma cells

are white blood cells that cooperate in defending the body against disease through recognition of foreign antigens and antibody production

T-lymphocytes, B-lymphocytes, and Natural killer (NK) cells

Lymphocytes are divided into 3 major groups:

NK cells

these cells are directly derived from the common lymphoid progenitor stem cell

NK cells

Part of the innate immune system by directly killing infected cells or tumor cells

resting cells

Lymphocytes are not end cells, rather they are ______________ and when stimulated, undergo mitosis to produce memory and effector cells (e.g. plasma cells).

lymphocyte recirculation

Lymphocytes move freely between the blood and lymphoid tissues, this is referred to as

age

Total blood lymphocytes vary with?

30% ; 34% (broader range: 30-40%, still normal)

At birth, blood lymphocytes represent about ___% of the total leukocytes and are the dominant leukocyte type within a few days from birth

In adults, they comprise about ____% of the total leukocytes in the blood

5%

In normal adults, approximately ___% of the total body lymphocytes is present in the circulating blood

60%-80%; 20%; 4%-29%

_______% of the blood lymphocyte pool is composed of T lymphocytes and approximately _____% is composed of B lymphocytes; around ________% are NK cells (variable depending if someone has an active infection or cancer, etc.

pluripotent, precursor cells of the yolk sac and liver

During embryonic development, lymphocytes arise from:

bone marrow

Later in fetal development and throughout the rest of the life cycle, the ___________ becomes the sole provider of hematopoietic stem cells, that later on becomes lymphocytes

Interleukin-1 (IL-1) and interleukin-6 (IL-6)

influences differentiation of the pluripotent stem cells into lymphoid stem cells.

Central/Primary Lymphatic Organs

responsible for the first few steps of lymphocyte development (bone marrow, thymus)

Peripheral/Secondary Lymphatic Organs

Where lymphocytes migrate to from the primary lymphoid organs. They either continue their development or they proliferate when stimulated.

- spleen, lymph nodes, tonsils, MALT such as Peyer's patches

Pro-B cell (progenitor B-cell), Pre-B cell (precursor B-cell), and Immature B cell

3 stages of Development of the B Lymphocytes and Plasma Cells

bone marrow

Development of the B Lymphocytes and Plasma Cells are all within the ____________

Development of B Lymphocytes and Plasma Cells

During these stages, the immature B lymphocytes have not been exposed to an antigen yet (antigen-naïve cells)

Plasma cells

____________ (most prominent effector cell) are fully differentiated B lymphocytes that are able to produce antibodies or immunoglobulins specific to the offending antigen that caused the initial stimulation (readily identified through its appearance).

CD138

Plasma cells also have specific cell surface markers, the most widely known being ?

T lymphocytes

develop in the thymus, located in the upper anterior mediastinum.

Pro-T cell, Pre-T cell, and Immature T cell

cytokines produced by the thymic cells

CD4+ T lymphocytes (T helper cells)

CD8+ T lymphocytes (T cytotoxic cells)

the two most prominent markers subdividing the antigen-naive T lymphocytes into two major categories:

Human Immunodeficiency Virus (HIV)

Targets the CD4+ T lymphocytes; as their levels get lower, the infected person becomes immunodeficient and these different diseases that constitute to AIDS affects them easily.

NC ratio

indicates the maturity of the cells as the cell matures, the size of nucleus decreases

CD4+ T lymphocytes (T helper cells)

- as soon as they are activated, they secrete substances that help B lymphocytes differentiate into memory and effector cell

CD8+ T lymphocytes (T cytotoxic cells)

- secretes substances that kill the target cell (like the action of NK cells)

cell activation.

The immature, antigen-naive T cells then migrate to secondary lymphatic organs and into blood, where, upon contact with an antigen results in ________

mature lymphocytes

Under normal conditions, only _____________ can be seen in peripheral blood at any age

Lymphoblasts,

Prolymphocytes, and

Mature Lymphocytes

the lymphoid series cells are classified as:

Lymphoblast

The first morphologically identifiable cell of the lymphocytic maturational series in the bone marrow

Lymphoblast

Size: 10-22 μm

Nucleus

▪ Shape: Round or oval, centrally or eccentrically placed

▪ N:C Ratio: 7:1 to 4:1

▪ Chromatin: Fine, lacy pattern to moderately coarse

▪ Nucleoli: 1-2 prominent (less prominent than myeloblast)

▪ Color: Reddish-purple

Lymphoblast

Cytoplasm

▪ Color: Moderate to dark blue ▪ Contents: smooth, no granules, occasional vacuoles

Peripheral smear of a patient with acute lymphoblastic leukemia

many lymphoblasts seen in peripheral blood which are not normally seen means

Prolymphocyte

May be seen in the bone marrow, thymus, and secondary lymphoid tissues

Prolymphocyte

N:C ratio ranges from 4:1 to 3:1 o Nuclear shape is usually oval or slightly indented

o Number of nucleoli varies from none, one, or two

o Chromatin pattern is highly condensed

Prolymphocyte

Cytoplasm is medium blue with a thin, darker blue rim; few azurophilic granules may be present

Mature Lymphocyte

Should be the only lymphoid cell that is normally seen in a blood smear

Resting lymphocytes

are usually small, their size approximates that of a normocytic red blood cell (often 7-8 μm in size)

Mature Lymphocyte

Size: 7-15 μm (nucleus is comparable in size than the normal RBC)

Nucleus

▪ Shape: Round or slightly indented, eccentric

▪ N:C Ratio: 3:1 (can be 2:1)

▪ Color: Deep purple-blue

▪ Chromatin: Coarse and clumped; heavily condensed

▪ Nucleoli: None visible

Mature Lymphocyte

Cytoplasm

▪ Color: Sky blue to deep blue

▪ Contents: scant and usually nongranular; few azurophilic granules may be seen

Variant/Reactive Lymphocyte

Present in viral diseases including infectious mononucleosis, cytomegalovirus, toxoplasmosis, hepatitis, and cat scratch fever

Variant/Reactive Lymphocyte

Represent antigenically stimulated lymphocytes that have increased DNA and RNA activity

Variant/Reactive Lymphocyte

Cell size: 10-25 μm

o Nucleus

▪ Shape: Oval, notched, indented, or elongated

▪ Nucleoli: One or more large nucleoli may be visible

o Cytoplasm is often abundant and stains pale to deep blue and darker at periphery; may be partially indented by adjacent red cells; few lavender granules and/or vacuoles

Variant/Reactive Lymphocyte

abundance of the cytoplasm, and red cells indenting the cytoplasmic borders

Plasma Cell

Fully differentiated B Lymphocyte

Plasma Cell

Not normally found in the circulating blood but are seen in the bone marrow in concentrations that do not normally exceed 2%.

Plasma Cell

Arise as the end stage of B-cell differentiation after antigenic stimulation

Plasma Cell

Responsible for producing specific immunoglobulins or antibodies directed towards the particular antigen.

o Overall size: 14 to 20 μm

Plasma Cell

Most striking feature: Nucleus is small and eccentrically-located (almost peripheral); chromatin is condensed and has a cartwheel configuration

Plasma Cell

Cytoplasm is abundant, dark blue with a visible lighter-staining area around the nucleus, called the hof, which represents the area occupied by the Golgi apparatus

distinctive dark blue cytoplasm

indicates active production and secretion of proteins, mainly antibodies

Plasma Cell

Cytoplasmic inclusions can include Russell bodies (small globules within the cytoplasm) which are acidophilic, refractile globules that represent gamma globulin (protein) secretions.

Monocyte

Differentiation into macrophages

● in areas of inflammation or infection (inflammatory macrophages)

Monocytes

are white blood cells (leukocytes) that function mainly as phagocytes in blood and in tissues, where they become macrophages.

Innate Immunity- recognition of bacterial pathogens, synthesize and secrete cytotoxic agents (nitric oxide)

Adaptive Immunity- as antigen-presenting cells (APCs), thus making them act in tandem with lymphocytes

"Housekeeping" cells- with removal of cell debris and dead cells from area of infection and tissue destruction/injury

Functions of Monocyte

2% to 11%; 1.33 x 10^9 /L

Monocytes make up between _________% of circulating leukocytes, equivalent to an absolute number of up to _________

granulocyte-monocyte progenitor (GMP)

Monocyte is derived from?

Macrophage colony-stimulating factor (M-CSF)

is the major cytokine responsible for the growth and differentiation of monocytes,

monoblasts, promonocytes, and monocytes

The morphologic stages of the monocyte development are the

myeloid series

The stem cell that eventually differentiates into the monocytic lineage is the same stem cell that differentiates into the __________

Pseudopods

are frequently seen at any stage at the monocytic development, but it is common in mature monocyte stage. It sometimes aid in phagocytosis and movement.

Monoblast

Only normally found in the bone marrow but even then, are rarely seen

o Size: 14-20 μm (large in comparison with RBCs)

o Nucleus (may be folded upon itself

● Shape: Round or oval

● N:C Ratio: 3:1 to 1:1

● Color: Light bluish-purple

● Chromatin: Fine and distinct

● Nucleoli: 1-5 o Cytoplasm

▪ Color: Blue-gray

▪ Contents: no granules (agranular)

Promonocyte

12 to 18 μm in diameter

o Nucleus is slightly indented or folded (more than monoblasts) o Chromatin pattern is delicate o Nucleolus: At least one apparent

o Cytoplasm is blue and contains scattered azure granules that are fewer and smaller than those seen in promyelocytes.

o Less prominent nucleoli (than monoblasts)

o Vacuoles are more commonly seen than in monoblast

o Granules are giving an impression of a ground-glass appearance.

Mature Monocyte

Can be considered as slightly immature cells whose ultimate goal is to enter the tissues and become macrophages

Mature Monocyte

Appear to be larger than neutrophils, because they tend to stick and spread out on glass or plastic

Mature Monocyte

Nucleus may be round, oval, or kidney-shaped but more frequently deeply indented (horseshoe-shaped) or folded on itself (irregular-shaped).

o Chromatin is loose (than other leukocytes), described as fine, 'lacelike'

Mature Monocyte

Blue-gray cytoplasm with fine azure granules or ground glass appearance

o Small cytoplasmic pseudopods or blebs and vacuolations are commonly seen (more common in mature monocytes, aids in movement and phagocytosis