AUTOIMMUNITY PART 1 BASICS

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-B27ANKYLOSING SPONDYLITIS, REACTIVE ARTHRITIS,
UVEITIS
HLA-DR2SYSTEMIC LUPUS ERYTHEMATOSUS [SLE]
HLA-DR3SLE, AUTOIMMUNE HEPATITIS, SJOGREN
SYNDROME, TYPE 1 DIABETES MELLITUS [DM]
HLA-DR4DM 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
NOD2expressed in Paneth & intestinal
epithelial cells, controls resistance to
gut commensal microbes
INFLAMMATORY
BOWEL DISEASE [IBD]
ATG16affects autophagy, role in maintaining
epithelial barrier & defense against
microbes
IBD
IRF5interferon 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