ORGANS OF THE IMMUNE SYSTEM
Organs of the Immune System:
- The immune system is made up of many different organs
and tissues dispersed throughout the body.
- PRIMARY lymphoid organs are the sites of lymphocyte birth &/ or maturation, in an
Ag independent fashion.
- SECONDARY lymphoid organs are the sites of mature lymphocyte selection and expansion in
an Ag dependent fashion.
Primary Lymphoid Tissues:
- generate and/or mature and educate cells of the immune
- maturation and central selection
- diversity created in an Ag independent fashion
Bone Marrow------------------ B cells
Thymus------------------------- T cells
Secondary Lymphoid Tissues:
- site where mature, immunocompetent lymphocytes are exposed
- Ag is collected and brought to tissue and lymphocytes
are exposed to Ag.
- lymph nodes-- Ag from intracellular tissue fluids
- spleen-------- blood-borne Ag
- MALT------- Ag from mucosal surfaces. Includes Peyer's
patches, tonsils, and adenoids
PRIMARY LYMPHOID ORGANS:
Organization is simple as they are sites of growth and
maturation and not sites where cells and Ag need to mix.
T cell progenitor cells enter the Thymus from Bone Marrow
to mature and to be "educated". The thymus is a flat, bilobed
organ situated over the heart. Lobes are covered by a CAPSULE and are divided into LOBULES by connective tissue
strands called TRABECULAE . The lobules are divided into 2 regions;
- outer compartment
- high thymocyte concentration
- site of progenitor T cell growth
- Nurse cells in outer area of cortex nourish thymocytes
- THYMIC EPITHELIAL CELLS
in the outer cortex, act to hold cells in place and to secrete factors
for differentiation and maturation including
- alpha 1-thymosin
- beta 4-thymosin
- Progenitor T-cells are DOUBLE NEGATIVE (CD 8-, CD 4-)
- start to develop TCR
- as they mature and move through the cortex they become
DOUBLE POSITIVE (CD4+, CD8+)
- cell density much less
- cells are mature and are SINGLE POSITIVE either CD 4+8- or CD 4-8+
Both the cortex and medulla are composed of a mesh of cells
forming the STROMA or framework of the tissue. These cells include epithelial cells,
Interdigitating cells, and macrophage. These cells make contact with thymocytes
to stimulate growth, carry out +ve and -ve selection, and remove dead cells
(90-95% of cells die). Chapters 9 and 10 will deal with the details of thymic
The Bursa of Fabricius is the site of B cell development
in birds. The bone marrow and possibly other sites (Peyer's patches in sheep
and cattle) play this role in mammals, but the lack of information on the
organ and how it works limits our knowledge of B cell development. Details
of B cell development and selection will be discussed later (chapter 11).
SECONDARY LYMPHOID ORGANS:
- site of stimulation of mature lymphocytes
- create sites for Ag-lymphocyte interaction
- Lymph, produced by the leakage
of fluid into tissue spaces (interstitial fluids) is returned to the blood
via lymphatic vessels of increasing size via the thoracic duct that empties
into the left subclavian vein.
- foreign Ag collects in lymph and is moved by the lymphatic
system along with lymphocytes to the lymphoid tissues to induce an immune
- lymphoid tissues can include simple lymphoid follicles
or more organized collections of follicles (Peyer's patches, tonsils, appendix)
or complex organizations of B and T cell rich organs (lymph nodes, spleen).
network of follicular dendritic cells and small resting B cells not yet
stimulated by Ag.
Ag stimulated ring of B cells around a Germinal
Center of proliferating B cells, B memory cells,
and plasma cells, mixed with macrophage and follicular dendritic cells.
Architecture provides microenvironment for lymphocytes
to effectively encounter and respond to Ag.
- Encapsulated bean shaped organ where reticular network
holds lymphocytes, macrophage, and dendritic cells
- Lymph enters the node via Afferent Lymphatic Vessels and lymph
born Ags entering node are trapped by phagocytic cells and reticular dendritic
- In the Paracortex (T-cell rich area) Ag is displayed
by APC to Th cells
- Th cells and Ag activated B cells
move to a primary follicle in the cortex and give rise to a secondary follicle
- Plasma cells produced in the secondary follicles move
to the medulla and secrete Ab which is collected in the lymph and leaves
through the Efferent Lymph Vessels
- During infections the lymph node may swell due to the
increased growth of lymphocytes with most lymphocytes entering the lymph
node via postcapillary venules.
- Large ovoid secondary lymphoid organ
- Covered by a capsule it too is divided into compartments
- Gains Ag from blood not lymph
- Tissue is divided into 2 types red pulp and white pulp,
which are separated by a diffuse marginal zone.
- Red pulp is an are of sinusoids populated by mf and RBCs.
This area is involved in the removal of old erythrocytes
- White pulp surrounds
the arteries forming the PERIARTERIOLAR
LYMPHOID SHEATH (PALS) populated by T cells
- The marginal zone, peripheral to the PALS, is rich in
B cells and contains primary follicles which can be Ag stimulated
- Ag and lymphocytes enter by the Splenic Artery, emptying
into the marginal zone. Ag is trapped by interdigitating dendritic cells
and moved to the PALS. Lymphocytes follow the same path.
MUCOSAL-ASSOCIATED LYMPHOID TISSUE (MALT)
- Mucosal membranes of the digestive, respiratory, and
urogenital systems are the major sites of Ag entry into the body
- MALT ranges from loose clusters of lymphoid cells in
the intestinal lamina propria, to more complex organizations as in the
Peyer's Patches, tonsils, and appendix.
- Very active areas of the immune system. The numbers of
plasma cells in the MALT >> then the number of plasma cells in the
spleen + lymph node + bone marrow.
- 3 locations, lingual, palatine, and nasopharyngeal (adenoids).
- defense against Ag entering from nasal or oral route
- 30-40 lymphoid nodules on the outer wall of the intestine
- Composed of follicles from which germinal centers develop
on Ag stimulation
- M cells specialized
cells at the mucosal surface sample and take Ag across the mucosal surface
forming inductive sites.
- Activated B cells leave follicles and migrate to diffuse
mucosal sites (MALT), differentiate into plasma cells, and secrete Ab (IgA).