PATHOLOGY, SECOND MBBS, MEDICAL COUNCIL OF INDIA, COMPETENCY BASED UNDERGRADUATE CURRICULUM FOR THE INDIAN MEDICAL GRADUATE, 2018

1. PA9.4
DEFINE AUTOIMMUNITY.
ENUMERATE AUTOIMMUNE
DISORDERS
Dr IRA BHARADWAJ
MCI TEACHER ID: PAT 2300569
KUHS FACULTY ID: M21512

2. TEXT BOOK REFRENCES
• ROBBINS BASIC PATHOLOGY
• HARSH MOHAN TEXTBOOK OF PATHOLOGY
• DAVIDSON’S PRINCIPLES AND PRACTISE OF MEDICINE
• OTHER STANDARD REFRENCES

3. SLO
• DEFINITON OF AUTOIMMUNITY
• BASIC MECHANISM OF AUTOIMMUNITY
• ENUMERATE AUTOIMMUNE DISORDERS MEDIATED BY B
LYMPHOCYTES
• ENUMERATE AUTOIMMUNE DISORDERS MEDIATED BY T
LYMPHOCYTES
• QUESTIONS AT END OF SECTION 9.7

4. AUTOIMMUNE DISEASES
DEFINITION
A GROUP OF DISEASE CHARACTERIZED BY
IMMUNE RESPONSE TO SELF ANTIGENS DUE TO
LOSS OF SELF TOLERANCE

5. MECHANISM OF AUTOIMMUNITY
BASICS
Breakdown of self tolerance due to:
• Genetic factors
• Environmental factors

6. MECHANISM OF AUTOIMMUNITY
BASICS: GENETIC FACTORS
• Mutations in genes controlling tolerance
• Familial predisposition
• Females > males
• Association with certain HLA types
• Associated with other genes, which control response to
immune regulation & microbes
• Before proceeding further, I would like to remind you that
each gene may have multiple roles & here we are focusing
only on their functions as related to our topic of discussion

7. MECHANISM OF AUTOIMMUNITY
GENETIC FACTORS: HLA & SOME COMMON AUTOIMMUNE
DISEASES
HLA AUTOIMMUNE DISEASE ASSOCIATION
HLA-B27 ANKYLOSING SPONDYLITIS, REACTIVE ARTHRITIS,
UVEITIS
HLA-DR2 SYSTEMIC LUPUS ERYTHEMATOSUS [SLE]
HLA-DR3 SLE, AUTOIMMUNE HEPATITIS, SJOGREN
SYNDROME, TYPE 1 DIABETES MELLITUS [DM]
HLA-DR4 DM TYPE 1
HLA-
DQ2&DQ8
COELIAC DISEASE

8. MECHANISM OF AUTOIMMUNITY
GENETIC FACTORS: NON HLA GENES INVOVED IN
IMMUNE REGULATION & AUTOIMMUNE DISEASES
GENES IN
IMMUNE
REGULATION
FUNCTION IN IMMUNE REGULATION AUTOIMMUNE DISEASE
ASSOCIATION
PTNP22 PROTEIN TYROSINE PHOSPHATASE AFFECTS
SIGNALING IN LYMPHOCYTES, ACTIVATING SELF
REACTIVE T CELLS
RHEUMATOID ARTHRITIS [RA],
TYPE 1 DM, INFLAMMATORY
BOWEL DISEASE [IBD]
IL23R INTERLEUKIN 23 RECEPTOR INDUCES
DIFFERENTIATION OF CD4+T CELLS INTO
PATHOGENIC TH17 CELLS
IBD, PSORIASIS, ANKYLOSING
SPONDITLITIS
CTLA4 AFFECTS REGULATORY T CELLS & SELF
TOLERANCE
RA, TYPE 1 DM
IL2RA ALPHA CHAIN RECEPTOR FOR INTERLEUKIN 2,
AFFECTS REGULATORY T CELLS & IMMUNE
RESPONSE
MULTIPLE SCLEROSIS, TYPE 1
DM

9. MECHANISM OF AUTOIMMUNITY
GENETIC FACTORS: NON HLA GENES INVOVED IN IMMUNE
RESPONSE TO MICROBES & AUTOIMMUNE DISEASES
GENES FUNCTION IN IMMUNE REGULATION
OF MICROBIAL INFECTION
AUTOIMMUNE
DISEASE ASSOCIATION
NOD2 expressed in Paneth & intestinal
epithelial cells, controls resistance to
gut commensal microbes
INFLAMMATORY
BOWEL DISEASE [IBD]
ATG16 affects autophagy, role in maintaining
epithelial barrier & defense against
microbes
IBD
IRF5 interferon regulatory factor 5, has role
in production of type 1 interferon
SYSTEMIC LUPUS
ERYTHEMATOSUS

10. MECHANISM OF AUTOIMMUNITY
BASICS: ENVIRONMENTAL FACTORS
• Molecular mimicry – cross reaction b/w antimicrobial Ab &
self Ag due to certain similarities in molecular structure
• Release of sequestered Ags, which normally do not come in
contact with immune system during development hence the
lymphocytes specific for such antigens are not deleted eg ,
sperm, lens, myelin

11. MECHANISM OF AUTOIMMUNITY
BASICS: OTHER FACTORS
• Infection associated with necrosis & inflammation, leading to
activation of costimulatory molecules & loss of anergy
(peripheral tolerance)
• Altered display of self Ags (epitope spreading) due to chronic
cell injury caused by UV, smoking, autoimmunity
• Polyclonal lymphocyte activation due to any cause
• Failure of apoptosis & clearance of apoptotic bodies
• Failure of T suppressor cell function

13. AUTOIMMUNE DISEASES MEDIATED BY B CELLS
TYPE II HYPERSENSTIVITY
• Autoimmune hemolytic anemia
• Autoimmune thrombocytopenia
• Autoimmune atrophic gastritis (intrinsic factor)
• Myasthenia gravis
• Graves disease
• Goodpasture syndrome
TYPE II & III HYPERSENSTIVITY
• Systemic lupus erythematosus [SLE]

14. AUTOIMMUNE DISEASES MEDIATED BY T
CELLS
TYPE IV HYPERSENSTIVITY
Type I diabetes
Multiple sclerosis
Hashimoto’s thyroiditis
Crohn’s disease [IBD]
Rheumatoid arthritis
Systemic sclerosis
Sjogren’s syndrome