The thymus and bone marrow are the primary lymphoid organs where lymphocytes mature and develop. The thymus is where T cells mature and undergo positive and negative selection to screen for self-reactivity before exiting as mature, functional T cells. The bone marrow is the site of B cell development in humans and mice. B cells proliferate and differentiate within the bone marrow, undergoing selection to eliminate self-reactive cells. While other species use different primary lymphoid organs like the bursa of Fabricius in birds, mammals primarily rely on the thymus and bone marrow.

1. ORGANS OF IMMUNE
SYSTEM

2. Organs of the Immune System
A number of morphologically and
functionally diverse organs and tissues
have various functions in the
development of immune responses.
These can be distinguished by function
as the primary and secondary
lymphoid organs.

4. Primary Lymphoid Organs
Immature lymphocytes generated in
hematopoiesis mature and become
committed to a particular antigenic
specificity within the primary
lymphoid organs.
Only after a lymphocyte has matured
within a primary lymphoid organ is
the cell immunocompetent (capable
of mounting an immune response).

6. THYMUS
The thymus is the site of T-cell
development and maturation.
It is a flat, blobbed organ situated
above the heart.
Each lobe is surrounded by a
capsule and is divided into lobules,
which are separated from each
other by strands of connective
tissue called trabeculae.

7. THYMUS

8. The outer compartment, or
cortex, is Each lobule is
organized into two
compartments:
densely packed with immature
T cells, called thymocytes.
The inner compartment, or
medulla, is sparsely populated
with thymocytes.

10. Many of these stromal cells interact
physically with the developing thymocytes.
Some thymic epithelial cells in the outer
cortex, called nurse cells, have long
membrane extensions that surround as
many as 50 thymocytes, forming large
multicellular complexes.

11. Other cortical epithelial cells
have long interconnecting
cytoplasmic extensions that
form a network and have
been shown to interact with
numerous thymocytes as
they traverse the cortex.

12. The function of the thymus is
to generate and select a
repertoire of T cells that will
protect the body from
infection.

13. As thymocytes develop, an
enormous diversity of T-cell
receptors is generated by a
random process that produces
some T cells with receptors
capable of recognizing antigen-
MHC complexes.

14. However, most of the T-cell
receptors produced by this
random process are incapable
of recognizing antigen-MHC
complexes and a small portion
react with combinations of self
antigen-MHC complexes
Function of the thymus

15. The thymus induces the death of
those T cells that cannot recognize
antigen- MHC complexes and those
that react with self-antigen– MHC
and pose a danger of causing
autoimmune disease.
More than 95% of all thymocytes
die by apoptosis in the thymus
without ever reaching maturity.

16. Freshman
•Double positive (DP) thymocytes as they
express both CD4 and CD8 molecules in
addition to TCRs.
1st Exam (Positive selection)
•Thymocytes must recognise MHC class I
(CD8) and MHC class II (CD4) will pass
their first exam and are promoted.
•Those that fail will die (Apoptosis)
•Survivor will be promoted to either CD4+ or
CD8+ single positive cells.
•These cells will move into the medulla of
thymus for 2nd Exam.
2nd Exam (Negative selection)
•SP will encounter antigen presenting
cells to see interaction with MHC or
peptide-MHC molecules.
•Those who show strong interaction with
pMHC are fated to die by programmed cell
death (apoptosis).
Graduation
•Those few cells that survive these two
exams are destined to "graduate" from
the thymus as T cells

17. THE THYMUS AND IMMUNE FUNCTION
The role of the thymus in immune function can
be studied in mice by examining the effects of
neonatal thymectomy, a procedure in which
the thymus is surgically removed from newborn
mice.
These thymectomized mice show a dramatic
decrease in circulating lymphocytes of the T-
cell lineage and an absence of cell-mediated
immunity.

18. Other evidence of the importance of the
thymus comes from studies of a
congenital birth defect in humans
(DiGeorge’s syndrome) and in certain
mice (nude mice) in which the thymus
fails to develop.
In both cases, there is an absence of
circulating T cells and of cell-mediated
immunity and an increase in infectious
disease.

19. Digeorge’s syn.
A Mutation on the 22nd Chromosome
Congenital birth defect in humans
Nude mice
Nude mouse is unable to produce T-cells,
and is, therefore, immunodeficient & increase
in infections
Absence of thymus and so T- cell deficiency
Nude mice
Thymus fails to develop Mutation in the gene
encoding a transcription factor

20. Aging and thymic function
Thymus diminishes in size with age
Thymus attains maximum size at puberty
Then degenerates with decrease in both
cortical & medullary cells
An increase in total fat content
 Ininfants the average wt. of thymus is 70g
In elders the average wt. is 3g
The age dependent involutions leaves an organ the reduced wt.
Evidence for the effect of age on the immune function
Thymus from 1day old mouse and 33 month was
removed and grafted to thymectomized adult.
Thymus form 1day –old- mouse showed large improvement in
immune function than mice receiving the 33 month old thymus

21. BONE MARROW
In humans and mice, bone marrow is the
site of B-cell origin and development.
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 and secrete
various cytokines that are required for
development

24. Like thymic selection during Tcell
maturation, a selection process
within the bone marrow
eliminates B cells with self-
reactive antibody receptors.
Bone marrow is not the site of B-
cell development in all species. In
birds, a lymphoid organ called the
bursa of Fabricius, a lymphoid
tissue associated with the gut, is
the primary site of B- cell
maturation.

25. In mammals such as primates and
rodents, there is no bursa and no single
counterpart to it as a primary lymphoid
organ.
In cattle and sheep, the primary
lymphoid tissue hosting the
maturation, proliferation, and
diversification of B cells early in
gestation is the fetal spleen.

26. Later in gestation, this function is
assumed by a patch of tissue
embedded in the wall of the intestine
called the ileal Peyer’s patch, which
contains a large number (>1010) B cells.
The rabbit, too, uses gut-associated
tissues such as the appendix as
primary lymphoid tissue for important
steps in the proliferation and
diversification of B cells.