Cellular and Molecular Basis of Immunity, A.K. Abbas ch 15

1. MECHANISMS OF AUTOIMMUNITY
(Cellular and Molecular Immunology A.K. Abbas et al, ch 15)
AHMET VARIS

2. AUTOIMMUNITY
• The term autoimmunity is often erroneously
used for any disease in which immune reactions
accompany tissue injury, even though it may be
difficult or impossible to establish a role for
immune responses against self antigens in
causing these disorders.

4. Immunologic Abnormalities Leading to
Autoimmunity
• Defective tolerance or regulation.
▫ Failure of the mechanisms of self-tolerance in T or B
cells, leading to an imbalance between lymphocyte
activation and control, is the underlying cause of all
autoimmune diseases
▫ There are four known causes for this;
 Negative selection of T and B cells
 Defective numbers and functions of regulatory T
lymphocytes
 Defective apoptosis of mature self-reactive lymphocytes
 Inadequate function of inhibitory receptors

5. Immunologic Abnormalities Leading to
Autoimmunity
• Abnormal display of self antigens.
▫ Increased expression and persistence of self
antigens that are normally cleared.
• Inflammation or an initial innate immune
response.
▫ By activating APCs, which overcomes regulatory
mechanisms and results in excessive T cell
activation. (why T cells are imp.)

6. Genetic Basis of Autoimmunity
• Mostly complex polygenic
• Genome-wide association studies, linkage analyses
in families, and interbreeding studies in animals
have revealed some of the common variations
(polymorphisms) of genes that may contribute to
different autoimmune diseases.
• Three main group of genes
▫ Association of MHC alleles with autoimmunity
▫ Polyphormism in Non-HLA genes
▫ Inherited single-gene abnormalities

7. MHC alleles with autoimmunity
• The strongest group that
associate with autoimmunity
• The realtion between HLA and
autoimmunity shows how
impotant T cells.
• But HLA allele is not, by itself,
the cause of the disease

8. Polyphormism in Non-HLA genes
• Associated with various
autoimmune diseases and may
contribute to failure of self-
tolerance or abnormal
activation of lymphocytes
• Combinations of multiple
inherited genetic
polymorphisms interacting
with environmental factors
induce the immunologic
abnormalities that lead to
autoimmunity.
• Epigenetic changes also affect
the diseases onset.

9. Inherited single-gene abnormalities
• Genes encoding complement proteins: Without complement
activation circulating immune complexes and apoptotic cell bodies
accumulate in blood
• FcγRIIB: Cause failure to control antibody-mediated feedback
inhibition of B cells.

10. Role of Infections and Other Environmental
Influences in Autoimmunity
• Infections
▫ Bystander activation: The infection results in the
activation of wrong T cells
▫ Molecular mimicry: Infectious microbes may
contain antigens that cross-react with self antigens, so
immune responses to the microbes may result in
reactions against self antigens.

12. • Other Environmental Influences
▫ Anatomic alterations in tissues, caused by
inflammation (possibly secondary to infections),
ischemic injury, or trauma, may lead to the
exposure of self antigens that are normally
concealed from the immune system
▫ Hormonal influences play a role in some
autoimmune diseases.

13. REFERENCES
• Mitchell Kronenberg & Alexander Rudensky, 2005, Regulation of
immunity by self-reactive T cells, doi:10.1038/nature03725
• Kazuhiko YAMAMOTO, 2004, Mechanisms of Autoimmunity,
JMAJ 47(9): 403–406
• Kornblum HI, Introduction to neural stem cells, 2007 Feb;38(2
Suppl):810-6.
• Wobus AM, Boheler KR, Embryonic stem cells: prospects for
developmental biology and cell therapy, Physiol Rev. 2005
Apr;85(2):635-78.
• Book: Cellular and Molecular Immunology. 8th edition. Abul K
Abbas
• Book: Basic Immunology:Functions and Disorders of the Immune
System, 4th edition, Abul K Abbas