Page 115 - Williams Hematology ( PDFDrive )

90 Part II: The Organization of the Lymphohematopoietic Tissues Chapter 6: The Organization and Structure of Lymphoid Tissues 91

presentation of antigens to T cells or the elaboration of immunomodu- Upon immune activation in response to antigen, the lymphocytes
latory cytokines. may remain in the spleen to sustain a primary or secondary immune
Collectively, the anatomy of the spleen allows the marginal zone response. Activation of B cells is initiated in the marginal zones that are
and red pulp to cull defective erythrocytes. As the blood passes slowly adjacent to CD4+ T cells in the PALS. Activated B cells then migrate
52
through the sinusoidal interendothelial slits and the fibroblast stroma, into germinal centers or into the red pulp. Lymphoid nodules appear
the erythrocytes must undergo alterations in shape to squeeze through and expand by recruiting lymphocytes from the blood and the periph-
the mechanical barrier generated by this filtration compartment. Nor- eral zone of the follicles, termed the mantle zone. These cells then pro-
mal red cells that are supple may pass through readily because the liferate and differentiate in the center of a lymphoid nodule, forming a
53
interendothelial slits can open to approximately 0.5 μm. However, ery- germinal center. In their path from the marginal zone to the follicles, B
throcytes containing large, rigid inclusions, such as plasmodium-con- cells pass into the PALS, where they remain in contact with T lympho-
45
taining erythrocytes, are delayed or sequestered. Antibody-coated red cytes for a few hours, allowing ample time for T- and B-cell interaction
cells, as present in autoimmune hemolytic anemia, are also recognized in response to antigens. If they are not recruited in an immune response
and removed by macrophages in the splenic red pulp. Polymorphisms to antigen, both T and B lymphocytes exit the spleen via deep efferent
of FcγRII (CD32) or FcγRIII (CD16) that affect immunoglobulin (Ig) G lymphatics, not the splenic veins.
binding in vitro can alter the efficiency of clearance of antibody-coated These efferent lymphatics are not distinguished as separate struc-
red cells in vivo. 46 tures within the PALS, being quite thin-walled and often packed with
When these filtration beds sequester imperfect red cells, the efferent lymphocytes. However, they are important in moving nonre-
blood pools inside the spleen, causing stasis and congestion. This stim- active lymphocytes out of the spleen and in producing high-hematocrit
ulates sphincter-like contraction of the distal vein, resulting in prox- pulp blood. After leaving the spleen, the efferent lymphocytes become
imal plasma transudation that produces a viscous luminal mass of the afferent lymphatics of the perisplenic mesenteric lymph nodes or
high-hematocrit blood. During episodes of enhanced red cell seques- empty into the thoracic duct. This duct empties into the left subclavian
tration, as occurs during malarial crises or hemolytic episodes in a small vein, thus returning the lymphocytes to the venous circulation.
proportion of patients with sickle cell disease, the splenic volume and
weight may increase 10- to 20-fold (Chap. 56). Although the white
47
pulp may enlarge, particularly in germinal centers, the marginal zones LYMPH NODES
and red pulp become greatly widened with pooled erythrocytes and
macrophages in this setting. The lymphoid nodes are secondary lymphoid tissues. They form part
of a network that filters antigens from the interstitial tissue fluid and
Regulation of Blood Volume lymph during its passage from the periphery to the thoracic duct. Thus,
The spleen also can play a role in modulating blood volume. Release of the lymph nodes are the primary sites of immune response to tissue
high-hematocrit blood through splenic contraction occurs in response antigens.
to activation of the baroreflex, which also may be activated during con-
ditions of decreased blood pressure and cardiac output. 48,49 On the other LYMPH NODE ANATOMY
hand, physiologic agents such as atrial natriuretic peptide, nitric oxide, The lymph nodes are round or kidney-shaped clusters of mononuclear
and adrenomedullin can induce fluid extravasation from the splenic cir- cells that normally are less than 1 cm in diameter (Fig. 6–7). A collage-
culation into lymphatic reservoirs. Excessive splenic extravasation can nous capsule surrounds a typical lymph node and has an indentation
50
contribute to the inability to maintain adequate intravascular volume called the hilus where blood vessels enter and leave.
during septic shock. There also is evidence that the splenic afferent and Lymph nodes typically are present at the branches of the lymphatic
renal sympathetic nerves play a role in maintaining renal microvascular vessels and form part of the extensive network of lymphatic channels
tone. This splenorenal reflex can influence blood pressure and, during that extends throughout the body. Several afferent lymphatic channels
50
septic shock, help promote renal sodium and water reabsorption and that drain lymph from regional tissues into the lymph node perforate
release of the vasoconstrictor angiotensin II. On the other hand, in portal the capsule of each lymph node. The lymph draining from the node
hypertension, the splenorenal reflex can promote renal sodium and leaves through one efferent lymphatic vessel at the hilus. The lymph
water retention and possibly play a role in the hemodynamic complica- from the node, in turn, empties into efferent lymphatic vessels that
tions of portal hypertension through neurohormonal modulation of the eventually drain into larger lymphatic channels leading eventually to the
mesenteric vascular bed. thoracic duct. The thoracic duct, in turn, drains into the left subclavian
vein, thus returning lymph into the systemic circulation.
Splenic Immune Function Clusters of lymph nodes are located strategically in areas that drain
The spleen and its responses to antigens are similar to those of lymph various superficial and deep regions of the body, such as the neck, axil-
nodes, the major difference being that the spleen is the major site of lae, groin, mediastinum, and abdominal cavity. The lymph nodes that
immune responses to bloodborne antigens, while lymph nodes are receive lymph that drains from the skin, termed somatic nodes, are
involved in responses to antigens in the lymph. Antigens and lympho- superficial. The lymph nodes that receive their lymph from the mucosal
42
cytes enter the spleen through the vascular sinuses, because the spleen surface of the respiratory, digestive, or genitourinary tract, termed vis-
lacks high endothelial venules. Upon entry, the lymphocytes home to ceral nodes, are usually deep within body cavities.
the white pulp. T cells, which express the chemokine receptor CCR7,
migrate to the PALS in response to CCL19 and CCL21, and B cells,
which express CXCR5, migrate to the lymphoid follicles in response to LYMPH NODE STRUCTURE
CXCL13. 37,51 Dendritic cells also express CCR7 and hence migrate to Beneath the collagenous capsule is the subcapsular sinus, into which
the same area as do naïve T cells. T and B cells migrate within these the afferent lymphatic channels drain (Fig. 6–8). This sinus is lined with
compartments for about 5 and 7 hours, respectively. In the absence of phagocytic cells. Fibrous trabeculae radiate from the medulla adjacent
an immune response, these cells migrate through a reticulum arranged to the hilus of the node to the subcapsular sinus, thus breaking the node
around the circumference of the central artery. into several follicles, called cortical follicles. These trabeculae, together

Kaushansky_chapter 06_p0085-0096.indd 91 17/09/15 5:53 pm