Immunology

ORGANS OF THE
IMMUNE
SYSTEM
Group - 2

Sr. No. Name Roll No. Signature

01. Mercy Fernandes SU160 103

02. Leander Barreto SU160 108

03. Jishnu Ravindran SU160 112

04. Rezelia Rodrigues SU160 120

05. Dicema Dias SU160 141

2017-18
Table of Contents
Abstract ........................................................................................................................................................... 2
Review of Literature................................................................................................................................... 3
Introduction................................................................................................................................................... 4
Organs of Immune System ...................................................................................................................... 5
History.......................................................................................................................................................... 5
The Lymphatic System ............................................................................................................................. 6
Primary/Central Lymphoid Organs ..................................................................................................... 6
1. Bone Marrow .............................................................................................................................. 6
2. Thymus ........................................................................................................................................ 7
Secondary Lymphoid or Peripheral Organs ...................................................................................... 8
1. Lymph Nodes ............................................................................................................................. 8
2. Spleen ........................................................................................................................................... 9
3. Mucosal Associated Lymphoid Tissue (MALT) ............................................................ 9
Cutaneous Associated Lymphoid Tissue (CALT) / Tertiary Lymphoid Tissue..................... 11
Conclusion .................................................................................................................................................... 12
References .................................................................................................................................................... 13

1
Abstract
The fully functional immune system involves so many organs, molecules, cells, and pathways in such
an interconnected and sometimes circular process that it is often difficult to know where to start!
Recent advances in cell imaging, genetics, bioinformatics, as well as cell and molecular biology, have
helped us to understand many of the individual players in great molecular detail. However, a focus on
the details can make taking a step back to see the bigger picture challenging, and it is often the bigger
picture that motivates us to study immunology. Indeed, the field of immunology can be credited with
the vaccine that eradicated smallpox, the ability to transplant organs between humans, and the drugs
used today to treat asthma.

Many technical advances, especially in the areas of imaging and sequencing, which have collectively
enhanced our understanding of immune function and cellular interactions, allowing us to view the
immune response in its natural anatomical context, and in real time.

2
Review of Literature
1. Dialogue between the CNS and the Immune System in Lymphoid Organs
The CNS influences the immune system in a more general fashion by regulating the systemic
concentration of humoral substances such as cortisol and epinephrine, whereas the autonomic nervous
system communicates specifically with the immune system according to local conditions. It seems
very likely that more examples of such specific local interaction between the autonomic nervous
system and the immune system will become obvious in the future. Since macrophage-derived IL-6
polarizes naive T cells to become effector Th2 cells, the neuroendocrine regulation of IL-6 production
by antigen-presenting macrophages would be a key factor in determining the type of immune response.
Modulating the nervous system, either centrally by psychopharmacological drugs or locally, at the
synaptic level, by transmitter antagonists, agonists and uptake-blockers, might be a promising
approach for immune therapy. Thus, the local interaction of the autonomic nervous system and the
immune system in lymphoid organs and non-lymphoid tissues represents the rationale for treating
selected inflammatory diseases by neuro pharmacological or psychological intervention.
2. Bone Marrow can function as a Lymphoid Organ
In this study we sought to better understand lymphocyte trafficking patterns and the function of
secondary lymphoid organs, such as the spleen, during the generation of virus-specific T cell
precursors. Treatment of mice with the Mel-14 mAb to CD62L, the lymph node homing receptor,
limits trafficking of naive T cells into lymph nodes through high endothelial venules. Administering
Mel-14 following respiratory infection with influenza virus forced the generation of primary virus-
specific CD4+ and CD8+ T cell precursors from the mediastinal lymph nodes to the spleen. However,
splenectomy did not seriously impede virus clearance from the lung and, despite a substantial reduction
of the total lymphocyte pool, the acute T cell responses in the regional lymph nodes were largely
normal. Mel-14 treatment of splenectomised mice did not affect clonal expansion of the virus-specific
T cells in the MLN, while the response in the cervical lymph nodes was still greatly inhibited. More
surprisingly, virus-specific T cell precursors were now detected from days 5 to 6 after infection in the
bone marrow (BM) of the splenectomised, Mel-14-treated mice. This was not due to contamination
with circulating T cells or infection of BM cells because the distribution profiles of precursor T cells
for PBL and BM diverged and PCR analysis showed no evidence of virus replication in the BM. It
appears that, under these conditions of disrupted lymphocyte trafficking, the BM can supplant the
secondary lymphoid tissue either as a site of primary immune response or as a cache for excess T cell
precursors.

3
Introduction

4
Organs of Immune System
The lymphoid organs are organized tissues containing large numbers of lymphocytes in a framework
of non-lymphoid cells. In these organs, the interactions lymphocytes make with non-lymphoid cells
are important either to lymphocyte development, to the initiation of adaptive immune responses, or to
the sustenance of lymphocytes. (Schmidt, Lang, & Heckmann, 2014)

History
Hippocrates, in the 5th century BC, was one of the first people to mention the lymphatic system. In his
work On Joints, he briefly mentioned the lymph nodes in one sentence. Rufus of Ephesus, a Roman
physician, identified the axillary, inguinal and mesenteric lymph nodes as well as the thymus during
the 1st to 2nd century AD. (Ambrose, 2006). The first mention of lymphatic vessels was in the 3rd
century BC by Herophilos, a Greek anatomist living in Alexandria, who incorrectly concluded that the
"Absorptive Veins of the Lymphatics," by which he meant the lacteals (Lymph Vessels of the
Intestines), drained into the hepatic portal veins, and thus into the liver. The findings of Ruphus and
Herophilos were further propagated by the Greek physician Galen, who described the lacteals and
mesenteric lymph nodes which he observed in his dissection of apes and pigs in the 2nd century AD.
(Ambrose, 2006) (Fanous, Phillips, & Windsor, 2007).
The next breakthrough came when in 1622 a physician, Gaspare Aselli, identified lymphatic vessels
of the intestines in dogs and termed them venae alba et lacteae, which is now known as simply the
lacteals. The lacteals were termed the fourth kind of vessels (the other three being the artery, vein and
nerve, which was then believed to be a type of vessel), and disproved Galen's assertion that chyle was
carried by the veins. But, he still believed that the lacteals carried the chyle to the liver (as taught by
Galen). (Ambrose, 2006). In 1652, Olaus Rudbeck (1630–1702), a Swede, discovered certain
transparent vessels in the liver that contained clear fluid (and not white), and thus named
them hepatico-aqueous vessels. (Flourens, 1859).

Galen's ideas prevailed in medicine until the 17th century. ‘It was thought that blood was produced by
the liver from chyle contaminated with ailments by the intestine and stomach, to which various spirits
were added by other organs, and that this blood was consumed by all the organs of the body’.

Alexander Monro, of the University of Edinburgh Medical School, was the first to describe the
function of the lymphatic system in detail. (Ambrose, 2006).

5
The Lymphatic System
The lymphatic system is part of the circulatory system and an important part of the immune system,
comprising a network of lymphatic vessels that carry a clear fluid called lymph directionally towards
the heart. Unlike the circulatory system, the lymphatic system is not a closed system. One of the main
functions of the lymph system is to provide an
accessory return route to the blood for the surplus three
litres. The other main function is that of defence in the
immune system. (Goldsby, Kindt, Osborne, & Kuby,
2003)
Lymph is very similar to blood plasma: it
contains lymphocytes. It also contains waste products
and cellular debris together with bacteria and proteins.

Associated organs composed of lymphoid tissue are

the sites of lymphocyte production. Lymphocytes are
concentrated in the lymph nodes. The system also
includes all the structures dedicated to the circulation
and production of lymphocytes (the primary cellular
component of lymph), which also includes the bone
marrow, and the lymphoid tissue associated with the
Fig: 1 - The lymphatic system
digestive system. (Tak W. & Saunders, 2008) Source: http://www.healthfavo.com/lymphatic_system.

The lymphatic system consists of lymphatic organs, a conducting network of lymphatic vessels, and
the circulating lymph. Lymphoid organs can be divided broadly into central or primary lymphoid
organs, where lymphocytes are generated, and peripheral or secondary lymphoid organs, where
adaptive immune responses are initiated and where lymphocytes are maintained. (Smith, Cunningham,
Lafferty, & Morris, 1969)

Primary/Central Lymphoid Organs

1. Bone Marrow
The bone marrow is a soft, flexible connective tissue found within the cavities of the bone. There are
two categories of bone marrow; the red bone marrow and the yellow bone marrow. The bone marrow
contains two main types of stem cells, the hematopoietic stem cells and mesenchymal stem cells
(multipotent stromal cells). The red marrow that is found in these bones consists of a sponge like
reticular framework located between long trabeculae. The spaces in this framework are filled with fat
6
cells, stromal fibroblasts and precursors of blood cells. These precursors mature and exit through the
dense network of vascular sinuses to enter the vascular circulation. In adult, much of the red marrow
is replaced by fatty tissue and becomes
yellow marrow.

B- Cell Maturation in Bone Marrow:

Arising from lymphoid progenitors,
immature B cells proliferate and
differentiate within the bone marrow,
and stromal cells within the bone
marrow interact directly with the B cells Fig: 2: Parts of a Long Bone and the Bone Marrow
Source: https://owlcation.com/stem/Bone-Marrow-Facts-Functions
and secrete various cytokines that are
required for development. Like thymic selection during T cell maturation, a selection process within
the bone marrow eliminates B cells with self-reactive antibody receptors. In humans, B cells are
functionally mature when they exit the bone marrow and enter circulation. Maturation of the B cells
involves a genetic rearrangement to bring the separate genes that make up the immunoglobulin heavy
and light chains together. (Goldsby, Kindt, Osborne, & Kuby, 2003)

2. Thymus
The thymus is the site of maturation of T cells. The thymus is a bilobed organ situated in the anterior
mediastinum. The thymus develops from the
third pharyngeal pouch. The parathyroid and
major vessels in the upper thorax also develop
from these pouches, so a defect in embryonic
development can result is greater or lesser
involvement of the parathyroid and major
vessels. The thymus has two distinct lobes
each of which consists of multiple lobules. The
lobules have a cortex that is densely packed
Fig: 3: Histology of Thymus Gland.
Source: https://www.researchgate.net/Thymus-Structure- Histology with rapidly dividing lymphocytes and a less
dense medulla in which most of the cells are resting, mature T cells. (Schmidt, Lang, & Heckmann,
2014)
The thymus is at its largest relative to body weight around the time of birth, but continues to grow in
size until puberty. Thereafter it involutes, and the lymphoid elements are progressively replaced with
fatty tissue, a process which continues throughout adulthood. (Schmidt, Lang, & Heckmann, 2014).

7
PreT cells enter the thymus through the post-capillary venules located at the juncture of the cortex and
medulla. The lymphocytes in the thymus called as thymocytes. (Goldsby, Kindt, Osborne, & Kuby,
2003)

They migrate out into the cortex under the influence of some unknown chemotactic factor(s) then back
through the cortex and into the medulla. During this time, they divide approximately every 12 hours.
Under the influence of several thymic hormones, the best known of which are thympoeitin and
thymosin, they gradually acquire the membrane and functional characteristics of mature T cells. The
mature T cells then leave the thymus through the post-capillary venules and enter circulation. (Smith,
Cunningham, Lafferty, & Morris, 1969)

Secondary Lymphoid or Peripheral Organs

An immune response is initiated only when an antigen comes into contact with lymphocytes that can
recognize and respond to it. To maximize contact between antigens and lymphocytes, lymphoid tissue
is organized such that tissue fluids (lymph) and blood are constantly filtered through beds of
lymphocytes. These beds are concentrated in areas that drain the most likely areas of access by
pathogens; i.e., the extremities and the mucosal surfaces. The spleen is the lymphoid tissue which
screens blood for pathogens that have escaped from the tissues whereas lymph node is the lymphoid
tissue which screens lymph for pathogens.
1. Lymph Nodes
Lymph nodes are small nodular aggregates of
lymphocyte rich tissue situated along lymphatic
channels throughout the body. Lymph node consists of
an outermost cortex and an inner medulla. The cortex
is composed of an outer cortex of B cells organized into
lymphoid follicles, and deep, or Para cortical, areas
made up mainly of T cells and dendritic cells.
When an immune response is underway, some of the Fig: 4: Histology of Lymph Nodes
Source: https://www.medicinenet.com/healthy _lymph
follicles contain central areas of intense B-cell nodes/article.html

proliferation called germinal centres and are known as secondary lymphoid follicles. These reactions
are very dramatic, but eventually die out as senescent germinal centres. Lymph draining from the
extracellular spaces of the body carries antigens in phagocytic dendritic cells and macrophages from
the tissues to the lymph node via the afferent lymphatic ducts.

8
Naive lymphocytes enter the node from the bloodstream through specialized post capillary venules
and leave with the lymph through the efferent lymphatic. Afferent lymphatic vessels drain fluid from
the tissues and also carry antigen-bearing cells and antigens from infected tissues to the lymph nodes,
where they are trapped. In the lymph nodes, B lymphocytes are localized in follicles, with T cells more
diffusely distributed in surrounding Para cortical areas, also referred to as T-cell zones. Some of the
B-cell follicles include germinal centres, where B cells are undergoing intense proliferation after
encountering their specific antigen and their cooperating T cells.

2. Spleen
The spleen consists of red pulp, which is a site of red blood cell destruction, interspersed with lymphoid
white pulp. An enlargement of a small section of the spleen shows the arrangement of discrete areas
of white pulp around central arterioles. Lymphocytes and antigen- loaded dendritic cells come together
in the Periarteriolar Lymphoid Sheath (PALS).
In each area of white pulp, blood carrying lymphocytes and antigen flows from a trabecular artery into
a central arteriole. Cells and antigen then pass
into a marginal sinus and drain into a trabecular
vein. The marginal sinus is surrounded by a
marginal zone of lymphocytes. Within the
marginal sinus and surrounding the central
arteriole is the periarteriolar lymphoid sheath,
made up of T cells.

Fig: 5: Anterior View and Histology of Spleen The follicles consist mainly of B cells; in
Source: http://www.flspinalcord.us/spleen-function-in-immune-
system secondary follicles a germinal center is
surrounded by a B-cell corona. Although the organization of the spleen is similar to that of a lymph
node, antigen enters the spleen from the blood rather than from the lymph.

3. Mucosal Associated Lymphoid Tissue (MALT)

The mucous membranes lining the digestive, respiratory, and urogenital systems have a combined
surface area of about 400 m2 and are the major sites of entry for most pathogens. These vulnerable
membrane surfaces are defended by a group of organized lymphoid tissues mentioned earlier and
known collectively as mucosal-associated lymphoid tissue (MALT).

Structurally, these tissues range from loose, barely organized clusters of lymphoid cells in the lamina
propria of intestinal villi to well-organized structures such as the familiar tonsils and appendix, as well
as Peyer’s patches, which are found within the submucosal layer of the intestinal lining.

9
The functional importance of MALT in the body’s defence is attested to by its large population of
antibody-producing plasma cells, whose number far exceeds that of plasma cells in the spleen, lymph
nodes, and bone marrow combined. It is classified under both secondary and tertiary lymphoid organs
because it act as both point of antigen encounter and entry respectively.

a. Tonsils:
The tonsils are found in three locations:
a. Lingual at the base of the tongue;
b. Palatine at the sides of the back of the
mouth;
c. Pharyngeal (adenoids) in the roof of the
nasopharynx.
All three tonsil groups are nodular structures
consisting of a meshwork of reticular cells and
fibers interspersed with lymphocytes, Fig: 6: Tonsillar Lymph Nodes
Source: http://www.keywordlister.com/tonsillar-lymph-nodes-
macrophages, granulocytes, and mast cells. The B 2004

cells are organized into follicles and germinal centres; the latter are surrounded by regions showing T-
cell activity. The tonsils defend against antigens entering through the nasal and oral epithelial routes.

b. Peyer’s Patches:
The lamina propria, which lies under the epithelial layer, contains large numbers of B cells, plasma
cells, activated TH cells, and macrophages in loose
clusters. Histologic sections have revealed more than
15,000 lymphoid follicles within the intestinal lamina
propria of a healthy child. The submucosal layer beneath
the lamina propria contains Peyer’s patches, nodules of
30–40 lymphoid follicles.

Like lymphoid follicles in other sites, those that compose

Peyer’s patches can develop into secondary follicles with
Fig: 7: Payer’s Patches in Intestinal Lumen
Source: http://www.flspinalcord.us/what-is-peyers-
germinal centres. The epithelial cells of mucous
patche membranes play an important role in promoting the
immune response by delivering small samples of foreign antigen from the lumina of the respiratory,
digestive, and urogenital tracts to the underlying mucosal-associated lymphoid tissue.

10
Cutaneous Associated Lymphoid Tissue (CALT) / Tertiary Lymphoid
Tissue
The skin is an important anatomic barrier to the external environment, and its large surface area makes
this tissue important in nonspecific (innate) defences. Many foreign antigens gain entry into the body
through the skin, so that it is called as tertiary lymphoid organ. The epidermal (outer) layer of the skin
is composed largely of specialized epithelial cells called keratinocytes. These cells secrete a number
of cytokines that may function to induce a local inflammatory reaction.

In addition, keratinocytes can be induced to express class II MHC molecules and may function as
antigen-presenting cells. Scattered among the epithelial-cell matrix of the epidermis are Langerhans
cells, a type of dendritic cell, which internalize antigen by phagocytosis or endocytosis.

These are similar to the intraepithelial lymphocytes of MALT in that most of them are CD 8 T cells,
many of which express T-cell receptors, which have limited diversity for antigen. These intraepidermal
T cells are well situated to encounter antigens that enter through the skin and some immunologists
believe that they may play a role in combating antigens that enter through the skin. The underlying
dermal layer of the skin contains scattered CD4 and CD8 T cells and macrophages. Most of these
dermal T cells were either previously activated cells or are memory cells.

11
Conclusion

12
References
Ambrose, C. (2006). Immunology's First Priority Dispute—An Account of the 17th-century Rudbeck–Bartholin
Feud. Cellular Immunology., 242(1): 1-8.

Fanous, M. Y., Phillips, A. J., & Windsor, J. A. (2007). Mesenteric Lymph: The Bridge to Future Management of
Critical Illness. Journal of the Pancreas., 8 (4): 374–399.

Flourens, P. (1859). A History of the Discovery of the Circulation of the Blood. In P. Flourens, A History of the
Discovery of the Circulation of the Blood (pp. 67–99. ). London.: Rickey, Mallory & Company.

Goldsby, R., Kindt, T., Osborne, B., & Kuby, J. (2003). Cells and Organs of the Immune System (Chapter 2). In R.
Goldsby, T. Kindt, B. Osborne, & J. Kuby, Cells and Organs of the Immune System (pp. 24-56). New
York: W. H. Freeman and Company.

Schmidt, R., Lang, F., & Heckmann, M. (2014, January 14). What are the Organs of the Immune System?
Retrieved from PubMed Health: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072579/

Smith, J., Cunningham, A., Lafferty, K. J., & Morris, B. (1969). The Role of the Lymphatic System and Lymphoid
Cells in the Establishment of Immunologcal Memmory. From the Department of Experimental
Pathology, John Cnrtin School of Medical Research, Australian National University, Canberra., 57-70.

Tak W., M., & Saunders, M. E. (2008). Primer to the Immune Response. In M. E. Saunders, Primer to the
Immune Response (pp. 28-32). San Diego, California.: Academic Press Publications.

13