1
Q
Be able to describe and identify the various developmental stages of erythropoiesis that lead to the formation of mature circulating erythrocytes.
A
a
2
Q
Be able to describe the difference(s) between red marrow and yellow marrow.
A
Yellow marrow
A. General points
1. Occupies much of the diaphysis of the long bones
2. Consists primarily of fat cells with blood vessels coursing through
Red marrow A. General points 1. Located in: a. Diploe of the skull b. Ribs c. Sternum d. Bodies of vertebrae e. Areas of cancellous bone f. Long and short bones of the body g. Iliac crest 2. Site of hemopoiesis 3. Red marrow is present in the long bones of neonates and children until 5 to 7 years of age. By 18 years of age almost all marrow of the limbs is yellow.
3
Q
Be able to describe the components of bone marrow stroma.
A
Cells
a. Fibroblasts
(1) Produce collagenous fibers and a delicate network of
reticular fibers found in the medullary cavity
(2) Reticular fibers may be produced by cells referred to
as “reticular cells”; whatever, both fibroblasts and
“reticular” cells are derived from mesenchyme
b. Macrophages
(1) Function to engulf and destroy imperfect red blood
cells, pieces from developing red blood cells, and
platelets.
(2) Phagocytose particulate matter in the sinusoids by
extending cytoplasmic processes between endothelial
cells of sinusoids
c. Fat-storing cells
(1) Predominate in yellow marrow, but are also present in
red marrow
d. Osteogenic cells
(1) Have the potential to differentiate into osteoblasts
(2) May produce a substance which causes bone marrow
precursor cells to locate in the medullary cavity of bones
e. Endothelial cells
(1) Form the lining of the sinusoids
2. Fibers
a. Collagenous fibers
(1) Support larger blood vessels in medullary cavity
(2) Reinforce tissue as a whole
b. Reticular fibers
(1) A network of fibers that support the blood forming cells
4
Q
Be able to explain the concept of colony forming units (CFUs).
A
a
5
Q
In general terms be able to describe the importance of differentiation and growth regulating factors on hematopoietic events.
A
a
6
Q
Be able to describe the difference between central (primary) and peripheral (secondary) lymphatic tissues.
A
a
7
Q
Be able to differentiate between and list the major encapsulated and non-encapsulated lymphatic tissues/organs.
A
a
8
Q
Be able to distinguish diffuse lymphatic tissue, lymphatic nodules, tonsils, lymph nodes, spleen, and thymus from one another.
A
a
9
Q
Be able to identify the various histological components/architectural features of the lymph node, thymus, and spleen.
A
a
10
Q
Myeloid tissue (bone marrow)
A
- Produces most blood cell types
- Found in the medullary cavity of bones
- Blood cell formation referred to as hematopoiesis
- Subdivisions of hematopoiesis:
a. Erythropoiesis – formation of red blood cells
b. Granulopoiesis – formation of granular leukocytes
c. Lymphopoiesis – formation of lymphocytes
d. Monopoiesis – formation of monocytes
e. Thrombocytopoiesis – formation of platelets
11
Q
Lymphatic tissue
A
- Consists of thymus, lymph nodes, spleen, and non-encapsulated lymph
nodules. T-lymphocytes differentiate in the thymus, while B-lymphocytes
differentiate in bone marrow tissue and subsequently become incorporated
into lymphatic tissue. - Characterized by an abundance of lymphocytes.
- Responsible for the immune defenses of the body.
12
Q
Yolk sac
A
- First site of hemopoiesis (2nd to 3rd week of embryonic life)
- Two cell types formed:
a. Endothelial cells
(1) Line the vascular system
(2) Originate from mesenchymal cells
b. Undifferentiated pluripotential stem cell
(colony forming unit = CFU)
(1) Originate from mesenchymal cells
(2) CFU seeds liver, spleen and bone marrow
13
Q
Liver
A
- Hemopoiesis begins about 6th week of fetal life and lasts until middle of
fetal life (major site of blood formation until middle of fetal life). - Erythropoiesis dominates and occurs extravascularly.
- Most red blood cells are nucleated at 7 weeks, but non-nucleated by
11 weeks.
14
Q
Spleen
A
- Hemopoiesis begins about 3rd month of fetal life.
- Erythropoiesis and granulopoiesis is greatest at 3rd-5th months, and lasts until 7th and 8th months of fetal life.
- Lymphopoiesis lasts throughout life.
15
Q
Bone
A
- Hemopoiesis beings in the 5th month of fetal life.
2. Clavicle first bone to develop a medullary cavity for myeloid tissue.
16
Q
Thymus
A
- Only lymphopoiesis occurs.
a. Form the T-lymphocytes - Lymphopoiesis beings in the 5th month of fetal life.
17
Q
Erythropoietin
A
- produced in kidney and other sites
- hypoxia stimulates formation of erythropoietin
- increases the number of hemoglobin-forming cells
(erythroblasts) by stimulating the stem cells (CFU-E)
to multiply and differentiate into hemoglobin-synthesizing
cells (proerythroblasts and basophilic erythroblasts)
18
Q
Proerythroblast (blast)
A
Nucleus: Round One or more nucleoli Cytoplasm: Basophilic due to ribosomes & polyribosomes Mitotic cell
19
Q
Basophilic erythroblast
A
Nucleus: Round
Chromatin in condensed (checker-board pattern)
No visible nucleoli
Cytoplasm:
Basophilic (more so than blast cell)-ribosomes essential for synthesizing more cell substance;
polysomes required for hemoglobin synthesis.
Mitotic cell
20
Q
Polychromatophilic erythroblast
A
Nucleus: Round and smaller More clumped No nucleoli Cytoplasm: Blue to pink ( decreased ribosomes, increased hemoglobin) Mitotic cell
21
Q
Orthochromatophilic erythroblast
A
Nucleus: Pyknotic (heterochromatic) Karyorrhexis occurs (extrusion of the nucleus occurs) Cytoplasm: Eosinophilic due to hemoglobin Not Mitotic
22
Q
Reticulocyte or Orthochromatophilic erythrocyte
A
Identified with cresyl violet
(see RNA reticular pattern)
Less than 1% in peripheral blood
23
Q
Myeloblast
A
Nucleus: Round or oval Chromatin finely granular One or more nucleoli Cytoplasm: Basophilic due to ribosomes & polyribosomes No granules present Mitotic cell 0.3 to 5% of marrow cells
24
Q
Promyelocyte
A
Nucleus: Round or oval Chromatin slightly courser Nucleoli present Cytoplasm: Granules present Azurophilic – appear first Specific Mitotic cell 4% of marrow cells
25
Myelocyte
```
Nucleus: Round
Chromatin more clumped
Nucleoli absent
Cytoplasm:
Granules present (specific increasing in
number while azurophilic decreasing
in number)
Mitotic cell
12% of marrow cells
```
26
Metamyelocyte
```
Nucleus: Not round
Chromatin condensing
Cytoplasm:
Granules present (specific numerous)
Not a mitotic cell
22% of marrow cells
```
27
Band
```
Nucleus: Not round (horseshoe shaped)
Chromatin condensed
Cytoplasm:
Granules present
Not a mitotic cell
```
28
Schema for identification of developmental stages of erythropoiesis and
granulocytopoiesis
A. Numerous azurophilic or specific granules present – if so, determine a-d and
proceed.
a. Nucleus – round or oval
1. Round, has nucleoli, basophilic cytoplasm, azure granules only =
Promyelocyte
2. Oval, no nucleoli, few to nearly filled with specific granules (may or
may not have azure) = Myelocyte
* b. Nucleus – indented = Metamyelocyte
c. Nucleus – "horseshoe" = Band
d. Nucleus – Segmented = Neutrophil
* Stages between myelocyte and mature forms for eosinophils and basophils
difficult to designate.
B. No granules present – if none determine a or b and proceed.
a. Hemoglobin not evident, cytoplasm entirely basophilic.
1. Nucleus, coarse, clumped chromatin, no nucleoli present –
cytoplasm intensely basophilic = Basophilic erythroblast
b. Hemoglobin evident in cytoplasm
1. Nuclear chromatin condensed – cytoplasm mixed basophilia and
acidophilia = Polychromatophilic erythroblast
2. Nucleus dense to pyknotic – near full complement of hemoglobin,
no basophilia in cytoplasm = Orthochromatophilic erythroblast
or normoblast
29
Lymphopoiesis (B-lymphocytes)
1. B-lymphocytes develop in the bone marrow.
T-lymphocytes develop in the thymus. Both B- and
T-lymphocytes populate other lymphatic organs.
2. In the bone marrow:
CFU-L --> lymphoblast --> prolymphocyte --> B-lymphocytes
3. B-lymphocytes seed lymphatic tissue, other than the thymus, and
there may differentiate further in response to antigens.
4. Lymphocytes, monocytes, reticular cells, plasma cells, and
megakaryocytes constitute 10-20% of the marrow cells.
30
Monopoiesis
1. The monocyte and its precursors comprise only 1 to 2% of the
bone marrow cells.
2. In the bone marrow: CFU-M --> monoblast --> promonocyte --> monocyte
3. Monocytes serve as precursors of macrophages.
31
Thrombocytopoiesis
1. General points
a. Involves the giant nucleated cell called the megakaryocyte
b. Cell undergoes endomitoses without cytokinesis or karyokinesis,
resulting in a polyploid cell with 16-64nDNA and multilobed nucleus
c. CFU-Meg --> megakaryoblast --> promegakaryocyte --> megakaryocyte
2. Forms platelets
a. Involves compartmentalization of the cell
(1) Membranes subdivide cytoplasm
(2) Compartments separate and form platelets
b. Thrombopoietin stimulates platelet formation
c. Platelet life is about 10 days
32
lymphoid tissue location
1. Central (primary) – where lymphocytes originate
a. Bone marrow – source of B-cells
b. Thymus – source of T-cells
2. Peripheral (secondary) – where lymphocytes respond to antigens
a. Mucosa-associated lymphatic tissue or nodular non-encapsulated
lymphatic tissue (lymphatic nodules, tonsils, Peyer's patches,
appendix, respiratory system)
b. Lymph nodes
c. Spleen
33
Characteristics of lymphatic tissue
1. Populated with lymphocytes (review from peripheral blood section)
a. Small lymphocytes
(1) B-lymphocytes
(2) T-lymphocytes
(3) Null cells
i. lack the surface characteristics of T- or B-cells
ii. constitute 5-10% of the peripheral blood cells
b. Large lymphocytes
(1) About 3 times the volume of small lymphocytes
34
Role of lymphocytes in immune responses
a. Recirculate continuously between the blood and lymph
b. Serve as immunocompetent cells, capable of responding to antigen
(1) B-lymphocytes differentiate into plasma cells which produce
humoral antibodies, or are retained in tissue as memory cells
(2) T-lymphocytes are involved in the cell-mediated immune
response (killer cells or cytotoxic T-lymphocytes, regulatory
cells, amplifier cells, etc.) or are retained in tissue as memory
cells. T-cells respond to an antigen usually when presented on
the surface of an accessory cell.
35
Follicular dendritic cells (FDCs)
(1) bind antibody-antigen complexes on surface of processes
| (2) do not endocytose and process antigen; thus these cells are not APCs
36
Diffuse lymphatic tissue
1. Seen in the GI tract, respiratory tract and any other sites when
lymphatic tissue accumulates
2. Loose
3. Dense
37
Nodular lymphatic tissue
1. Seen scattered throughout the digestive, respiratory and urinary
systems in the loose connective tissue beneath wet epithelial membranes.
2. Represent local immune responses to antigens.
3. Characterized by solitary lymphatic nodules (follicles).
38
Secondary lymphatic nodules
General features
a. Do not appear until after birth
b. Disappear in absence of antigen and reappear with re-exposure to antigen
c. Thymus required for development
d. Numerous during childhood, but decline in number with age
2. Cells of germinal center
a. Large and medium sized lymphocytes (primarily B-cells)
(1) Mitotic cells
(2) Known as lymphoblasts (activated lymphocytes)
b. Small lymphocytes (both B- and T-cells)
(1) More numerous: seldom seen dividing
(2) Enlarge and divide when stimulated by antigen
Macrophages (APCs)
(1) Morphological features of macrophages, which seems to be variable
(2) Frequently contain remains of digested lymphocytes and other
digested material
(3) Process antigens for presentation to lymphocytes
d. Follicular dendritic cells (FDCs)
(1) Lightly eosinophilic cytoplasm and large, euchromatic nucleus
(2) Bind antigen-antibody complexes to their surface via Fc receptors
e. Developing plasma cells found especially at periphery of germinal center
C. Lymphatic nodules (follicles) are present in lymph nodes and spleen, but are not
present in the thymus. If present in the thymus, suggests a pathological condition
39
Functions of non-encapsulated lymphatic tissue
A. Traps antigen
B. Produces lymphocytes in response to antigens
1. Antigens stimulate lymphocyte proliferation
2. Differentiation of B cells occurs
C. Destroys antigen
40
Cortex
a. Lymphoid tissue supported by a reticular fiber meshwork
b. Numerous lymphocytes and lymphatic nodules with germinal centers
(1) Lymphatic nodules are transitory and have a tail which
extends into the medulla as the medullary cords
c. Stromal cells
1. Superficial cortex
a. Located between capsule and outer limits of germinal center
b. Contain a majority of B-lymphocytes
2. Mid-cortex
a. Area containing primarily the germinal centers
b. Contain a majority of B-lymphocytes, together with other
cells of the germinal center
3. Deep cortex (paracortex)
a. Area between germinal centers and medullary cords
b. Contain a majority of T-lymphocytes, which extend into the
area between the nodules of the superficial and mid-cortex,
and also into the medulla
41
Medulla
a. Lymphoid tissue supported by a reticular fiber meshwork and
stromal cells
b. Contains the medullary cords
c. Contains numerous small lymphocytes, differentiating and mature
plasma cells, and macrophages
42
Sinuses
1. Lined by endothelial cells with large intercellular gaps
2. Macrophages, lymphocytes and reticular cells found in all sinuses.
Lymphocytes enter lymphatic sinuses, and leave lymph node through
efferent lymphatics, becoming part of the re-circulating lymphocytes.
Macrophages enter the lymph fluid and blood, but become trapped in
the lung where they are disposed of by entering the lung parenchyma.
43
Lymph flow through lymph node:
1. Afferent lymphatic vessels
2. Subcapsular (marginal) sinus
3. Trabecular (peritrabecular) sinus
4. Paracortical (subcortical) sinus
5. Medullary sinus
6. Efferent lymphatic vessel
44
Blood flow through lymph node:
1. Arterial vessels (hilum)
2. Trabecular vessels
3. Arterioles and capillaries
4. Post-capillary venules
a. Outer cortex (superficial and mid)
45
Deep cortex (paracortex)
Lined by simple cuboidal endothelium: (HEV's = high endothelial
venules)
(2) Site of passage of T-lymphocytes from the blood vessels
(venules) into the lymphatic tissue for recirculation via
the efferent lymphatics back to the blood vascular system
(3) Thymectomy at birth results in:
i. Depletion of lymphocytes from the deep and mid-cortex
ii. A change in venule endothelium from cuboidal to squamous
46
Circulating lymphocytes – enter from
1. Post-capillary venules
a. More than 95% of lymphocytes in the efferent lymphatic vessels
are derived from lymphocytes which migrated through the post-
capillary venules
b. Lymphocytes enter the deep cortex and internodular cortex
c. Path of recirculating T-lymphocytes
(1) Afferent arterioles
(2) Pre-capillary arterioles
(3) Capillaries
(4) Post-capillary venules (HEV's)
(5) Lymphatic tissue
(6) Lymphatic sinuses
(7) Efferent lymphatic vessels
2. Afferent lymphatics
47
Functions of lymph nodes
A. Lymph filter
1. Macrophages remove about 99% of bacteria entering through
afferent lymphatic vessels.
B. Produces lymphocytes which are added to the vascular system, and
Which may go to some other body site.
C. Produce antibodies. Antibodies are produced by plasma cells.
Plasma cells rarely enter lymphatic sinuses or are found in the
peripheral blood.
48
Cortex of thymus
Reticular cells
a. Form a loose cellular network which supports the developing
T-lymphocytes
b. Derived from endoderm
c. Characterized by a large nucleus with a prominent nucleolus,
and voluminous eosinophilic cytoplasm
d. Invaded during embryonic development by T-lymphocyte stem
cells which proliferate in the peripheral cortex and enter the
circulation at the corticomedullary junction
e. Produces thymic hormones (thymosin, thymopoietins, serum
thymic factor, thymic humoral factor) – function to:
(1) Promote differentiation of stem cells into T-lymphocytes
(2) Induce formation of T-lymphocyte surface markers
f. Help form the blood-thymus barrier, which prevents antigens
from entering the thymic cortex
2. Macrophages
a. Phagocytic cells
b. Function to destroy dying or abnormal cells during process
of T-lymphocyte formation
Lymphocytes – three regions distinguished
a. Outer region
(1) Stem cells enter from vascular system, give rise to
lymphoblasts, and undergo mitosis
(2) Contain largest lymphocytes in the cortex
(3) Maturing cells move toward medulla
b. Middle region
(1) Consists of differentiating or maturing cells derived
from outer region
(2) Cell proliferation continues
c. Inner region
(1) Contain the smallest lymphocytes of the cortex
(2) Cell division not evident
(3) Mature T-lymphocytes in this region enter blood vessels
at the corticomedullary junction, from which they go to
thymic dependent zones of the lymphatic organs
49
Medulla of thymus
1. Consists primarily of epithelial reticular cells, and some
lymphocytes and other connective tissue cells and fibers
2. Characteristic feature is the thymic (Hassall's) corpuscles
50
Medulla
a
51
white pulp of spleen
a. Periarterial lymphatic sheaths
(1) Surround the white pulp artery or central artery
(2) Contain primarily T-cells
b. Splenic (lymphatic) nodules
(1) Scattered throughout the splenic pulp
(2) Contain primarily B-cells except in area associated
with white pulp or central artery
52
red pulp of spleen
a. Splenic sinuses (sinusoids)
(1) Vascular passageways
(2) Lined by specialized endothelial cells
b. Splenic cords (Billroth cords)
(1) Located between the sinuses
(2) Contain red blood cells, granulocytes, lymphocytes,
macrophages, platelets, plasma cells, and reticular cells
and fibers
53
marginal zone of spleen
(1) A transition zone between the red and white pulp where small
blood vessels empty their blood
(2) Recirculating lymphocytes return to enter either the periarterial
lymphoid sheath or the splenic nodule
54
Functions of spleen
A. Forms antibodies in response to blood-borne antigens. The spleen is
the body's main source of circulating antibody.
B. Removal and destruction of defective blood cells, platelets, debris, and
suspended particulate matter is accomplished by macrophages.
C. Concentrates and stores blood cells and platelets.
D. In prenatal life forms red blood cells, granulocytes, lymphocytes and platelets.
Operation Unthinkable (1)
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