Auto Immunity

Autoimmunity and
Autoimmune Diseases
Immune system
The human immune system is

a host defense system comprising
many biological structures and
processes within an organism that
protects against disease
Immune system
Innate immune system
Adaptive
immune system
Invertebrates
Vertebrates
Vertebrates
Innate immune system
Ancient immune recognition system of host cells
bearing germline incoded pattern recognition
receptors that recognize pathogens and trigger
a variety of mechanisms of pathogen elimination
 Cells of the innate immune system include:
natural killer (NK) cell lymphocytes ，
monocytes/macrophages ， dendritic cells ，
neutrophils ， basophils ， eosinophils ， tissue
mast cells ， and epithelial cells
Adaptive immune system
Recently evolved system of immune responses
mediated by T and B lymphocytes
Immune responses by these cells are based on specific
antigen recognition by clonotypic receptors that are
products of genes that rearrange during development
and throughout the life of the organism
Additional cells of the adaptive immune system
include various types of antigen presenting cells
Antibody- Antigen-
 B cell-produced molecules  recognition molecules or as
encoded by genes that rearrange secreted molecules in plasma
during B cell development and other body fluids.
consisting of immunoglobulin Antigens-foreign or self-
heavy and light chains that molecules that are recognized
together form the central by the adaptive and innate
component of The B cell immune systems resulting in
receptor for antigen. Antibody immune cell triggering, T cell
can exist as B cell-surface activation ， and/or B cell
antibody production
Key properties
The normal immune system has three key properties:
A highly diverse repertoire of antigen receptors that
enables recognition of a nearly infinite range of
pathogens
Immune memory, to mount rapid recall immune
responses
 Immunologic tolerance ， to avoid immune damage
to normal self-tissues
Immune system
One of the central features of the immune system is
the capacity to mount an inflammatory response to
potentially harmful foreign materials while
avoiding damage to self-tissues
The development of potentially harmful immune

responses to self-antigens is, in general, prohibited
When autoimmunity is induced
by an inciting event, such as
infection or tissue damage from
trauma or ischemia, the
autoreactivity is in general
self-limited
Autoimmunity and Autoimmune
Diseases
Autoimmunity Autoimmune disease
refers merely to the The essential feature of an
presence of antibodies or autoimmune disease is that
T lymphocytes that react tissue injury is caused by
with self-antigens and does the immunologic reaction
not necessarily imply that of the organism against its
the self-reactivity has own tissues
pathogenic consequences
Ig M
Polyreactive
autoantibodies
are present
throughout life
MECHANISMS PREVENTING AUTOIMMUNITY
1 . Sequestration of self-antigens
2. Generation and maintenance of tolerance or anergy
a. Central deletion of autoreactive Lymphocytes
b. Peripheral anergy of autoreactive Lymphocytes
c. Receptor replacement in autoreactive Lymphocytes
3. Regulatory mechanisms
a. Regulatory T cells
b. Regulatory ß cells
c. Regulatory mesenchymal cells
d. Regulatory cytokines
e. Idiotype network
In general ， abnormal immune
responses require both:
exogenous trigger (bacterial or viral

infection or cigarette smoking)
endogenous abnormalities in the cells of

the immune system
MECHANISMS OF AUTOIMMUNITY
 I. Exogenous
A. Molecular mimicry
ß. Superantigenic stimulation
C. Microbial and tissue damage-associated adjuvanticity
 II . Endogenous
A. Altered antigen presentation
ß. Increased T cell help
D. Apoptotic defects or defects in clearance of apoptotic material
E. Cytokine imbalance
F. Altered immunoregulation
G. Endocrine abnormalities
Microbial superantigens (staphylococcal protein A and
staphylococcal enterotoxins) can stimulate a broad range
of T and B cells through specific interactions with
selected families of immune receptors
If autoantigen-reactive T and/or B cells express these

receptors, autoimmunity may develop
Alternatively ， molecular mimicry or cross-reactivity

between a microbial product and a self-antigen may
lead to activation of autoreactive Iymphocytes
Additional factors
age
sex (many autoimmune diseases are far more
common in women)
 exposure to infectious agents
environmental contacts
IMMUNOPATHOGENIC MECHANISMS
Antibody-mediated processes
 Cell-mediated processes
Antibody-mediated
MECHANISMS TARGET DISEASE
 Blocking or inactivatlon a Chain of the nicotinic Myasthenia gravis
acetylcholine receptor
Phospholipid-ß2 Antiphospholipid syndrome
glycoprotein I complex
Insulin receptor Insulin-resistant diabetes mellitus
Intrinsic factor Pernicious anemia
 Stimulation TSH recepto r (LATS) Graves' disease
Proteinase-3 (ANCA) Granulomatosis with polyangiitis
Epidermal cadherin Granulomatosis with polyangiitis
Desmoglein 3 Pemphigus vulgaris
 Complement activation α3 Chain of collagen IV Goodpasture's syndrome
 Immune complex Double-stranded DNA Systemic lupus erythematosus

Immunoglobulin
 Opsonization Platelet Gpl l b: l l l a Autoimmune thrombocytopenic
purpura
Autoimmune hemolytic anemia
 Anti body-dependent Thyroid peroxidase Hashimoto's thyroiditis
thyroglob u l i n
 cellular cytotoxicity Rh antigens I antigen Rheumatoid a rthritis
cell-mediated
TARGET DISEASE
Cytokine production Rheumatoid arthritis ，
multiple sclerosis ，
type 1 diabetes mellitus
Cellular cytotoxicity Type 1 diabetes mellitus

AUTOIMMUNE DISEASES
PRESUMPTIVE EVIDENCE FOR IMMUNOLOGIC PATHOGENESIS
Major Criteria
 1 . Presence of autoantibodies or evidence of cellular reactivity to self
 2. Documentation of relevant autoantibody or Iymphocytic infiltrate in the
pathologic lesion
 3. Demonstration that relevant autoantibody or T cells can cause tissue
pathology
a . Transplacental transmission
b. Adaptive transfer into animals
c . In vitro impact on cellular function
Supportive Evidence
 1. Reasonable animal model
 2. Beneficial effect from immunosuppressive agents
 3. Association with other evidence of autoimmunity
 4. No evidence of infection or other obvious cause
DISEASES OF THE AUTOIMMUNE
SPECTRUM
Organ Specific (Graves' disease, Hashimoto's thyroiditis, Autoimmune
polyglandular syndrome, Type 1 diabetes mellitus, Insulin-resistant diabetes
mellitus, Immune-mediated infertility, Autoimmune Addison's disease,
Pemphigus vulgaris, Pemphigus foliaceus, Dermatitis herpetiformis, Autoimmune
alopecia...)
Organ Nonspecific (Systemic)-- Systemic lupus erythematosus,

Rheumatoid arthritis, Systemic necrotizing vasculitis, Granulomatosis
with polyangiitis, Antiphospholipid syndrome, Sjögren's syndrome.
Treatment of
AUTOIMMUNE DISEASES
Suppressing the induction of autoimmunity
Restoring normal regulatory mechanisms
Inhibiting the effector mechanisms

Therapies that prevent target organ
damage or support target-organ
function remain important in the
management of autoimmune disease

Auto Immunity

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Auto Immunity

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Autoimmunity and

The human immune system is

The development of potentially harmful immune

exogenous trigger (bacterial or viral

endogenous abnormalities in the cells of

If autoantigen-reactive T and/or B cells express these

Alternatively ， molecular mimicry or cross-reactivity

 Immune complex Double-stranded DNA Systemic lupus erythematosus

Cellular cytotoxicity Type 1 diabetes mellitus

Organ Nonspecific (Systemic)-- Systemic lupus erythematosus,

Suppressing the induction of autoimmunity

Restoring normal regulatory mechanisms

Inhibiting the effector mechanisms

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