1. TOLERANCE PATHWAYS OF B
AND T CELLS
PRESENTED BY
ENA ATHAIDE
MSc – 2,Sem- 4
INSTITUTE OF SCIENCE, MUMBAI.

2. Immunological Tolerance
• Immunological tolerance is the failure to mount an
immune response to an antigen.
• Natural or "self" tolerance. This is the failure (a good
thing) to attack the body's own proteins and other
antigens. If the immune system should respond to "self",
an autoimmune disease may result.
• Induced tolerance. This is tolerance to external
antigens that has been created by deliberately
manipulating the immune system.

3. Mechanisms of unresponsiveness to
self antigens
• Central tolerance: Immature self-reactive lymphocytes that
recognize self antigens in generative (“central”) lymphoid organs
die by apoptosis; other fates .
• Peripheral tolerance: Mature self-reactive lymphocytes that
recognize self antigens in peripheral tissues are inactivated
(anergy), killed (deletion) or suppressed.
• “Clonal ignorance”: Mature self-reactive lymphocyte clones do not
encounter or respond to self antigens.
• In normal individuals it is not known which self antigens induce
tolerance by which mechanism.

4. Central T cell Tolerance

5. Peripheral tolerance
APC TCR
T cellCD28
Activated
T cells
APC
TCR
Functional
unresponsivenessAnergy
Apoptosis
(activation-induced
cell death)APC
Deletion
APC
Block in
activation
Suppression
Regulatory
T cell
Off signals
Activated
T cell

6. Tolerance in B lymphocytes
Central tolerance:
• Deletion of immature cells by high-affinity
antigen recognition in the bone marrow.
• Some immature cells may change their antigen
receptors when they encounter antigens in the
bone marrow (“receptor editing”)
Peripheral tolerance:
• Anergy
• Exclusion from lymphoid follicles, death because
of loss of survival signals.

7. Tolerance in B lymphocytes
• Cannot respond to most antigens unless they
receive help from T helper cells.
• B cells are formed and mature in the bone
marrow. In humans, over half of the
developing B cells produce a BCR able to bind
self components.

8. Central and peripheral
Tolerance in B cells

9. Research
Galectin-1 as a potential therapeutic target in autoimmune disorders and
cancer.
Galectin-1, a member of a family of highly conserved glycan-binding
proteins, has emerged as a regulator of immune cell tolerance and
homeostasis. This endogenous lectin widely expressed at sites of inflammation
and tumour growth, has been postulated as an attractive immunosuppressive
agent to restore immune cell tolerance and homeostasis in autoimmune and
inflammatory settings.On the other hand, galectin-1 contributes to different
steps of tumour progression including cell adhesion, migration and tumour-
immune escape, suggesting that blockade of galectin-1 might result in
therapeutic benefits in cancer. Recent findings implicating galectin-
glycoprotein lattices as selective regulators of inflammatory responses have
provided new insights into the understanding of the molecular bases of
galectin-1-induced immunoregulation.
Here the authors review the dual role of galectin-1 as a selective
immunosuppressive agent in T helper (TH)1 and TH17-mediated
inflammatory/autoimmune disorders and a potential therapeutic target in
cancer and metastasis.

10. References
• Kindt, T. J., & Kuby, J. (2007). Kuby immunology.
Macmillan,Chicago.
• Salatino, Mariana, Diego O. Croci, Germán A. Bianco, Juan
M. Ilarregui, Marta A. Toscano, and Gabriel A. Rabinovich.
"Galectin-1 as a potential therapeutic target in autoimmune
disorders and cancer." (2008): 45-57.
• Abbas, A. K., Lichtman, A. H., & Pillai, S. (2005). Cellular and
molecular immunology (Vol. 20005). Philadelphia:
Saunders,Chicago.
• Tizard, I. (1992). Veterinary immunology. An
introduction (No. ed. 4). WB Saunders Co. Chicago