immunity

1. AUTOIMMUNITY

2. Self/Non-self Discrimination
Autoimmunity is a problem of self/non-
self discrimination.

3. Autoimmunity
• 5 % to 7% adult affected.
• Two third women.
• More than 40 human diseases
autoimmune in origin.

7. Autoimmunity & Left-
handedness
• LEFT handed individuals more affected.
• 11% of left handed & 4% of right handed.
• Reasons for this are obscure.
• left-handedness & immune malfunction
may both result from abnormal endocrine
function in fetal life.

8. 1) Tissue destruction
Diabetes: CTLs destroy insulin-producing b-cells in pancreas
2) Antibodies block normal function
Myasthenia gravis: Ab binds acetylcholine receptors
3) Antibodies stimulate inappropriate function
Graves’ disease: Ab binds TSH receptor, mimics thyroid-stimulating
hormone-Activates unregulated thyroid hormone production
4) Antigen-antibody complexes affect function
Rheumatoid arthritis: IgM specific for Fc portion of IgG -
IgM-IgG complexes deposited in joints inflammation
Effects of autoimmunity

9. Mechanisms of autoimmunity
1. Ag released from hidden location.
2. Antigen generated by molecular changes.
3. Molecular mimicry.
4. Alteration in Ag processing.
5. Infection.
6. Genetic factors.

10. Mechanisms of autoimmunity
7. Lymphocytes abnormalities.
8. Failure of central tolerance.
9. Overcome of peripheral tolerance.
10. Polyclonal lymphocytes activation.

11. Ag related from hidden
location
Many self Ag are found in hidden location eg. CNS ,TESTES ,EYE
(CORNEA)
organ damage
Hidden Ag released
Reaches blood stream
Encounter Ag sensitive cells
Stimulate autoimmunity

12. Damage to immunologically
privileged sites can lead to
autoimmunity

13. Antigen generated by molecular
changes
• Development of completely new epitopes on normal protein. eg RF
immuno coaglutinine.
Mechanism of formation of RF :
Ab + Ag
new epitopes exposed on Fc region of Ab
Stimulate the formation of RF
Establishment of disease like Rheumatiod
artheritis and SLE

14. Molecular mimicry
Sharing of epitopes between an infectious agent
and its host.
Antibodies directed against the infectious
agents starts reacting with normal self Ag.
Triggers autoimmunity.

15. Alteration in Ag processing
• T cell may fail to develop tolerance to an
self Ag simply because it is not efficiently
procured.
• If something wrong happens in the
processing, an autoimmune disease may
be triggered.
• This usually happens at the site of
inflammation resulting in modified Ab.
• Eg. Thyrotoxicosis , Diabetes.

16. Infection
• Here autoimmunity is not due to infectious
agent itself ,but results from disregulation of
host immune response by the microbes.
This may be due to :
• Polyclonal lymphocyte activation.
• Enhanced stimulation of co stimulator.
• Alteration of self Ag (cross reactive neo-Ag)

17. Genetic factors
• The important genes that regulate the development of
autoimmunity are located within MHC.
• MHC have got critical role in maturation of T cell & induction of
Immune Response .
• MHC ll genes are directly responsible for antigen processing and
presentation.
• The structure of Ag binding groove will determine , if specific Ag
will trigger an immune response.
Class I MHC Associations
Ankylosing Spondylitis HLA-B27
Grave’s Disease HLA-B8
Class II MHC Associations
Rheumatoid Arthritis HLA-DR4
Sjogren’s Syndrome HLA-DR3
SLE HLA-DR3, DR2
Type I Diabetes HLA-DR3
Celiac Disease HLA-DR3
Myasthenia Gravis HLA-DR3
Multiple Sclerosis HLA-DR2

18. Lymphocytes abnormalities
• Primary abnormalities either in B cell or T cell.
• Since these cells are critical regulators of all IR.
• MHC presentation of all antigenic peptide to
these cells will be defective, in case these cells
are abnormal.
• Abnormalities in lymphocytes could affect any
one of the mechanism that normally maintains
self tolerance.

19. Failure of central tolerance
Inside primary lymphoid organ;
 Positive selection
 Negative selection (Deletion of self reacting
T cells in thymus apoptosis).
Failure of central tolerance starts Autoimmune
diseases.

23. POLYCLONAL LYMPHOCYTE
ACTIVATION
Stimulation of non deleted self reacting
lymphocytes. These are activated by some
activators:
• LPS-
Polyclonal B Cell Activator
• BACTERIAL SUPER ANTIGEN-
Polyclonal T Cell Activator

31. Rheumatiod Arthritis
• Auto-immune disorder which results in
inflammation of the synovial lining of the joint
and cartilage destruction.
• This result in loss of function.
• Affects 1% of adults.

36. Treatment for autoimmunity
• Immunosuppression (e.g., prednisone, cyclosporin A)
• Removal of thymus (some MG patients)
• Plasmapheresis (remove Ab-Ag complexes)
• T-cell vaccination (activate suppressing T cells??)
• Block MHC with similar peptide
• anti-CD4 monoclonal Ab
• anti-IL2R monoclonal Ab