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CHAPTER 6 THYMIC ANATOMY
The thymus is located in the superior mediastinum, overlying, in order,
THE ORGANIZATION AND the left brachiocephalic (or innominate) vein, the innominate artery,
the left common carotid artery, and the trachea. It overlaps the upper
STRUCTURE OF LYMPHOID limit of the pericardial sac below and extends into the neck beneath the
upper anterior ribs. It receives its blood supply from the internal tho-
TISSUES racic arteries. Venous blood from the thymus drains into the brachioce-
phalic and internal thoracic veins, which communicate above with the
inferior thyroid veins.
Arising from the third and fourth branchial pouches as an epithe-
Aharon G. Freud and Michael A. Caligiuri* lial organ populated by lymphoid cells and endoderm-derived thymic
epithelial cells, the thymus develops at about the eighth week of ges-
tation. The thymus increases in size through fetal and postnatal life
2
and remains ample into puberty, when it weighs approximately 40 g.
3
SUMMARY Thereafter, the size progressively decreases with aging as a consequence
of thymic involution. The cause of thymic involution is likely in part a
4
5
The lymphoid tissues can be divided into primary and secondary lymphoid result of the influence of glucocorticoid hormones. Nonetheless, there
organs. Primary lymphoid tissues are sites where lymphocytes develop from is evidence that T lymphocytes continue to develop throughout life,
6
progenitor cells into functional and mature lymphocytes. The major primary potentially including in some extrathymic sites.
The volume of the thymus can be estimated by sonography. In one
lymphoid tissue is the marrow, the site where all lymphocyte progenitor cells study of 149 healthy term infants within 1 week of birth, there was a
reside and initially differentiate. This organ is discussed in Chap. 5. The other significant correlation between the estimated thymic volume and the
primary lymphoid tissue is the thymus, the site where progenitor cells derived weight of the infant. However, no correlation was apparent between
3,7
from the marrow differentiate into mature thymus-derived (T) cells. Second- the estimated thymic volume and the infant’s sex, length, or gestational
ary lymphoid tissues are sites where lymphocytes undergo additional matura- age. Also, there was no apparent correlation between estimated vol-
tion and also interact with each other and with nonlymphoid cells to generate ume and the proportions of CD4+ T cells or CD8+ T cells found in the
immune responses to antigens. These tissues include the spleen, lymph nodes, blood. The estimated thymic volume of healthy infants increases from
3
and mucosa-associated lymphoid tissues such as tonsils. The structure of these birth to 4 and 8 months of age and then decreases. Most of the indi-
tissues provides insight into how the immune system discriminates between vidual variation at 4 and 10 months of age appears to correlate with
self-antigens and foreign antigens and develops the capacity to orchestrate a breastfeeding status, body size, and, to a lesser extent, illness. Breastfed
variety of specific and nonspecific defenses against invading pathogens. infants at 4 months of age have significantly larger estimated thymic
volumes than do age-matched formula-fed infants with similar thymic
volumes at birth. 8

THYMIC ARCHITECTURE
THE THYMUS A longitudinal fissure divides the thymus into two asymmetrical lobes, a
larger right and a smaller left, that are derived from the right and left bran-
The thymus is the site for development of thymic-derived lymphocytes, chial pouches, respectively. These two developmentally separate parts of
or T cells. In this organ, developing T cells, called thymocytes, differ- the thymus are easily separated from each other by blunt dissection.
entiate from lymphoid stem cells derived from the marrow into func- Each lobe of the thymus is divided into multiple lobules by fibrous
1
tional, mature T cells. It is here that T cells acquire their repertoire of septa that extend inward from an outer capsule. Each lobule consists
specific antigen receptors to cope with the antigenic challenges received of an outer cortex and an inner medulla (Fig. 6–1). The cortex con-
throughout one’s life span. Once they have completed their maturation, tains dense collections of thymocytes (developing immature T cells)
the T cells leave the thymus and circulate in the blood and through sec- that cytologically appear as lymphocytes of slightly variable size with
ondary lymphoid tissues. scattered, rare mitoses. The lighter-staining medulla is loosely arranged
and more sparsely populated by mature thymocytes and characteristic
tightly packed whorls of squamous-appearing epithelial cells, called
thymic or Hassall corpuscles (Fig. 6–2). These appear to be remnants of
degenerating cells and are rich in high-molecular-weight cytokeratins.
Hassall’s corpuscles are thought to serve a critical role in the develop-
Acronyms and Abbreviations: AIRE, autoimmune regulatory gene; APECED, autoim- 9
mune polyendocrinopathy-candidiasis-ectodermal dystrophy; CT, computed tomog- ment of regulatory T cells.
raphy; GALT, gastrointestinal-associated lymphoid tissue; Ig, immunoglobulin; IL, The thymus contains several important cell types that serve a
interleukin; ILC, innate lymphoid cell; MALT, mucosa-associated lymphoid tissue; variety of functions including supporting the maturation of thymo-
MHC, major histocompatibility complex; NK, natural killer; PALS, periarteriolar lym- cytes into mature T cells. There are several types of specialized epi-
10
phoid sheath; PGA syndrome, polyglandular autoimmune syndrome; r, correlation thelial cells within the thymus. The three main categories of thymic
coefficient; T, thymus-derived; TCR, T-cell receptor. epithelial cells are the medullary epithelial cells, which are organized
into clusters; the cortical epithelial cells, which form an epithelial net-
work; and the epithelial cells of the outer cortex. The epithelial cells in
the cortex and medulla often have a stellate shape, display desmoso-
* This chapter was prepared by Thomas J. Kipps in the 8th edition and much of mal intercellular connections, and likely function as support cells to
the text has been retained. developing thymocytes by providing important growth factors such

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