This presentation deals with Autoimmunity its Mechanism and classification

1. AUTOIMMUNITY ITS
MECHANISM AND
CLASSIFICATION WITH
SUITABLE EXAMPLES
Dr Akshay Shetty
Associate Professor
SSRAMCH Inchal

2. Contents
Objectives
Definition of
Autoimmunity
Mechanism of
Autoimmunity
Classification
with suitable
examples
Summary References
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3. Objectives
By the end of the presentation
the students must be able to ---
1. Define Autoimmunity
2. Describe mechanism of
Autoimmunity
3. Classify Autoimmunity with
suitable examples
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4. Autoimmunity refers to an aberration in the body's normal
development such that the immune system mounts an attack
against its own cells.
The aetiology behind autoimmune diseases is multifactorial, with
Genetic
Hormonal ,
Environmental factors
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5. To protect against a wide variety of
pathogens, host receptors on
lymphocytes undergo extensive
gene rearrangement and somatic
mutation processes to create a
repertoire of receptors that
recognize a vast amount of antigens.
Upon recognition, the adaptive
immune system delivers a message
of either immunity or tolerance.
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6. Tolerance refers to the process where "self" antigens found normally in the
body are prevented from mounting an immune response, while "non-self"
antigens mount the appropriate response.
When the tolerance process fails, autoimmunity can manifest.
Both central and peripheral tolerance are crucial in preventing autoimmunity
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7. Central Tolerance
• T-cell Central Tolerance
• B-cell Central Tolerance
Peripheral Tolerance
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8. Central Tolerance
• The central regions of maturation for T-lymphocytes and B-
lymphocytes are in the thymus and bone marrow, respectively.
Therefore, mechanisms of tolerance present in these locations
are referred to as central tolerance
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9. T-cell Central Tolerance
The process for immature T-
cells begins when they arrive
in the thymus from the bone
marrow and
encounter proteins bound to
major histocompatibility
complexes (MHC).
MHC molecules are cell-
surface antigens present in
vertebrates, and in humans,
they are called human
leukocyte antigens (HLA).
There are three subtypes,
HLA-A, HLA-B, and HLA-C,
that comprise MHC Class I.
MHC I antigens are
expressed on almost every
cell type in the body.
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10. • Other subtypes, namely HLA-DP, HLA-DQ, and HLA-DR, belong
to MHC Class II. MHC II molecules are found less ubiquitously,
namely in cells of the reticuloendothelial system such as
macrophages and B-lymphocytes.
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11. The central
tolerance process
begins in the
cortical epithelial
region of the
thymus.
Endogenous
proteins are bound
either to MHC I or
MHC II molecules,
which then interact
with immature
double-positive T-
lymphocytes
that express both
CD4+ and CD8+.
T-lymphocytes that
bind with an
intermediate affinity
are signaled to
survive and mature
into single-positive
lymphocytes, thus
creating
lymphocytes that
are either CD4+ or
CD8+. This is known
as positive
selection.
These cells then
move to the
corticomedullary
junction region,
where each CD4+ or
CD8+ T-lymphocyte
becomes exposed to
MHC molecules that
are bound to self-
peptides. If binding
at this stage is of
high affinity, the
respective T-cell will
undergo death by
apoptosis. This is
known as negative
selection.
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12. 1
Central tolerance is
the initial way in
which autoreactive T-
cells are prevented
from making it out
into the systemic
circulation. This is an
effective process
largely due to the
medullary epithelial
cells in the thymus.
2
To present a
comprehensive array
of self-peptides found
in all organs of the
body, these cells
express autoimmune
regulator
transcription factors
(AIRE) that cause
increased expression
of tissue-restricted
antigens found in
other parts of the
body.
3
Expression of tissue-
restricted antigens
aids with efficient
negative selection.
4
Autoimmunity can
develop in cases
where mutations
arise in AIRE, causing
less expression of
tissue-restricted
antigens
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13. B-cell Central Tolerance
The central
tolerance process
for immature B-
cells occurs in the
bone marrow.
B-cells play a
significant role in
the immune
response to
various pathogens
through the
production of
antibodies, also
known as
immunoglobulins.
These antibodies
are glycoprotein
molecules with a
heavy chain and a
light chain that
bind to antigens,
such as those of
microbial origin,
and facilitate their
destruction.
There are five classes of
immunoglobulins- IgG,
IgM, IgA, IgE, and IgD-
which play various roles
in protecting the body
against acute and chronic
infections and from
pathogens of various
types, including bacteria,
viruses, parasites, and
fungi. In cases where
individuals cannot
produce certain or all
antibodies, recurrent
infections are likely to
occur.
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14. • Which play various roles in protecting the body against acute
and chronic infections and from pathogens of various types,
including bacteria, viruses, parasites, and fungi. In cases where
individuals cannot produce certain or all antibodies, recurrent
infections are likely to occur
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15. Peripheral Tolerance
• After T-lymphocytes and B-lymphocytes leave the thymus and
bone marrow, they enter peripheral immune organs and tissues
such as the spleen and lymph nodes. In these regions, peripheral
tolerance mechanisms prevent autoimmunity from arising in the
case that autoreactive lymphocytes made it through all central
tolerance processes.
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16. • Systemic Autoimmune Diseases
• Organ-Based Autoimmune Diseases
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17. Systemic Autoimmune Diseases
Systemic Lupus Erythematosus: at least four of the following
eleven criteria must be present:
malar rash, discoid rash, photosensitivity, oral ulcers, arthritis,
serositis, kidney disorder [most often lupus nephritis],
hematologic disorder, neurologic disorder, immunologic disorder,
and antinuclear antibody positivity
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19. • Scleroderma: excessive deposition of
collagen in the skin and internal organs;
can present in both local and systemic
forms (limited cutaneous systemic and
diffuse cutaneous systemic); limited
cutaneous systemic form is associated
with CREST syndrome of calcinosis,
Raynaud phenomenon, esophageal
involvement, scleroderma, and
telangiectasia
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20. • Sarcoidosis: noncaseating granulomas in organs
throughout the body, most commonly
manifesting in the lungs as bilateral hilar
lymphadenopathy but can also have ocular,
dermatologic, cardiac, gastrointestinal,
neurologic, and endocrine manifestations
• Rheumatoid Arthritis: symmetric synovial
inflammation and morning stiffness > 30 minutes,
and various extra-articular manifestations
including rheumatoid nodules, amyloidosis, and
systemic vasculitis
• Celiac Disease: duodenal villous atrophy and
associated foul-smelling diarrhea and
malabsorption upon consumption of gluten-
containing foods
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21. Organ-Based Autoimmune Diseases
Type 1 Diabetes: autoantibodies to pancreatic islet cells leads to lack of
production of insulin, resulting in hyperglycemia, polyuria, and polydipsia
Crohn Disease: inflammatory bowel disease characterized by patchy, transmural
lesions that can affect the entire gastrointestinal tract, with the possibility of
fistulas, erythema nodosum, and pyoderma gangrenosum
Bullous Pemphigoid: a subepidermal blistering disease caused by autoantibodies
attacking the hemidesmosome; associated with symmetric tense bullae on the
trunk, inner thigh, and flexures as well as urticaria, pruritus, and eczema
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22. Ankylosing Spondylitis: sacroiliac joint tenderness, lower back pain, peripheral
arthritis, dactylitis
Henoch-Schonlein Purpura: vasculitis associated with purpuric rash, arthralgia,
gastrointestinal bleeding, abdominal pain, and nephritis
Multiple Sclerosis: demyelination caused by chronic inflammation of the
central nervous system results in spinal cord syndromes, optic neuritis,
brainstem and cerebellar syndromes, and cognitive impairment
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23. Summary
1.Define
Autoimmunity
1
Describe
mechanism of
Autoimmunity
2
Classify
Autoimmunity
with suitable
examples
3
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24. References
https://www.ncbi.nlm.nih.gov/books/NBK
576418/#:~:text=Autoimmunity%20refers
%20to%20an%20aberration,factors%20all
%20playing%20a%20role
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25. Thank you
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