An undergraduate lecture on immunologic tolerance, it's various types and how a breakdown of tolerance contributes to the pathogenesis of autoimmune diseases. Additionally a small quiz at the end to gauge the students' learning.

1. Dr Muhammad Omair Riaz
MBBS, FCPS (Immunology)
Consultant Immunologist

3. Should be able to:
 Define tolerance
 Enumerate types of tolerance
 Give an overview of their mechanisms
 List important autoimmune diseases
 List important drugs in treatment of autoimmunity

4.  Review of Medical Microbiology &
Immunology
 http://immense-immunology-
insight.blogspot.com

5. Definition:
 Tolerance is specific immunologic
unresponsiveness
 i.e., an immune response to a certain antigen
[or epitope] does not occur, although the
immune system is otherwise functioning
normally

6.  “Deletion of self-reactive T-cell precursors
in the thymus”
 In general, antigens that are present during
embryonic life are considered “self ” and do
not stimulate an immunologic response (i.e.,
we are tolerant to those antigens)

7.  T CellTolerance
 B CellTolerance

8.  Types:
 Central tolerance: Thymus
 Mechanism:
▪ Clonal deletion
 Peripheral tolerance: Outside thymus
 Mechanism
▪ Clonal anergy

12.  Peripheral tolerance is necessary because
some antigens are not expressed in the
thymus and therefore some self reactive T
cells are not killed in the thymus.
 There are several mechanisms involved in
peripheral tolerance

14. NormalT Cell Activation In case of clonal anergy

15.  Types:
 Central tolerance: Bone marrow
 Mechanism:
▪ Clonal deletion and receptor editing
 Peripheral tolerance: Outside bone marrow
 Mechanism
▪ Clonal anergy

16.  To avoid clonal deletion , B cells undergo
receptor editing
 Upto 50% of all B cells undergo receptor
editing

17.  Age
 Lower age enhances tolerance
 Structure & dose of antigens
 Lower doses induce tolerance
 Administration of immunosuppressive drugs
 Induces tolerance
 Type of cells involved
 T cells become tolerant more readily
 Administration of a cross-reacting antigen
 Terminates tolerance.

20. Definition
 Loss of tolerance to self antigens

21.  The most important step in the production of
autoimmune disease is the activation of self-
reactive helper (CD4)T cells.
 These self-reactive cells can induce either
cell-mediated or antibody-mediated
autoimmune reactions, respectively

22. These can be:
 Genetic
 Endogenous/ Hormonal
 Environmental

24. 1. Molecular mimicry
 Immune response against a substance can induce
immune response against it’s molecular
analogues
2. Alteration of Normal Proteins
3. Release of SequesteredAntigens
 Due to disease etc
4. Epitope Spreading
5. Failure of regulatoryT cells

25.  SLE
 RA
 PemphigusVulgaris
 IDDM
 Grave’s disease
 Coeliac disease

28. Time for The
mandatory Quiz!!!

29.  Immunologic tolerance is an example of
1. Incomplete immune response
2. Ineffective immune response
3. Partial immune response
4. Absent immune response
5. No immune response

30.  What induces tolerance?
1. Deletion of self reactiveT cells in thymus
2. Deletion of self reactiveT cells in Bone marrow
3. Deletion of self reactive B cells in thymus
4. Deletion of self reactive B cells in Bone marrow

31.  Negative selection ofT cells in thymus is an
example of:
1. Clonal anergy
2. Clonal deletion
3. Receptor editing
4. Breakdown of tolerance
5. None of the above

32.  All of these are mechanisms of peripheralT
cell tolerance except
1. Clonal anergy
2. Clonal deletion
3. Inhibition by regulatoryT cells
4. Positive selection of self reactiveT cells
5. None of the above

33.  All of these are mechanisms of autoimmunity
except:
1. Molecular mimicry
2. Release of Sequestered Antigens
3. Epitope Spreading
4. Failure of regulatoryT cells
5. Negative selection of self reactiveT cells

34.  Following factors are a cause of autoimmune
disease, except:
 Genetic factors
 Hormonal factors
 Environmental factors
 Dietary factors
 None of the above
You got it wrong coz you were busy whatsapping!

35. Download the presentation from
www.slideshare.net/omairriaz