Autoimmune

Diseases
Dantes, Ralph Lawrence A.
Lachica, Kristin Jane Mariz G.
Pangilinan, J.A. Miguel P.
Pasion, Angela M.
Quitasol, Marion Coleen E.
Racelis, Riza Alyana K.
Reyes, Cherry Rose T.
Roldan, Michael B.
Salvador, Pamela Marie M.
Simbe, Irvinne Keith S.
Superable, Aries Glenn B.
Tan, Bernadette Irish T.
Torno, Benedict Ian A.
Villadolid, Carla Angela D.
Zaballero, Cesar Paolo L.
 Autoimmunity
• “auto”- self
• Breakdown of the immune system’s ability to
discriminate between “self” and “non-self”
• A breakdown of mechanisms responsible for
tolerance
 Lack of immune response to self antigens

Self-Recogniti on
(TOLERANCE)
Elimination of cells with potential to react strongly with self antigens

Tolerance
Self-Recognition (TOLERANCE)
●
Acquir
●
Develo
ps in Ce ed
outside
Per
thymus
during
fetal
ntr the
thymus iph
;
●
life
Acquir al occurs
in
eral
ed by
the
proces
Tol circula
tion Tol
●
Involve
s called
clonal era s
mature
era
deletio
n nce lympho
cytes nce
Self-Recognition (TOLERANCE)
●
Acquir
●
Develo
ps in Ce ed
outside
Per
thymus
during
fetal
ntr the
thymus iph
;
●
life
Acquir al occurs
in
eral
ed by
the
proces
Tol circula
tion Tol
●
Involve
s called
clonal era s
mature
era
deletio
n nce lympho
cytes nce
 Peripheral tolerance:

Programmed cell death of cell reactive T

Apoptosis
●

cells

Clonal ●
Self reactive T cells are not activated because
proper costimulation does not occur.
anergy
Clonal ●
This means self reactive T cells ignore self
antigen. May be due to physical separation or
ignorance antigens are very small amount.
 T cell
Abnormal release of
precursors Thymus
autoreactive T cells

Selected T cells

CENTRAL
TOLERANCE

PERIPHERAL
TOLERANCE
anergy /
deletion/
suppression
Bone marrow
 cells
or or
cells
Immune system attacks

of of
the organs
Immune systemit was
attacks
designed to protect
the organs it was

Presence
designed to protect

autoantibody
Presence
autoreactive
autoantibody
autoreactive
Autoimmune diseases
Caused

of self poisoning
Caused

of self poisoning
autotoxicus”- fear
breakdown
by by

autotoxicus”-
“horror fear
tolerance
breakdown
thethe

“horror
tolerance
of self-
lossloss
of self-
or or
 Factors Influencing Development of
Autoimmunity

Genetic Factors
●
Increased incidence in twins
●
Women > Men
●
Hormones
●
Familial aggregates
●
Presence of certain HLAs

Patient Age
●
Incidence increases with age
●
Peak at about 60-70 years

Exogenous Factors/ Environmental Conditions

●
Ultraviolet radiation
●
Drugs
●
Viruses
●
Chronic infectious diseases
 Causes of Autoimmunity-breakdown of
tolerance

Inappropria
Release of Polyclonal te Lymphokin
Molecular
Sequestere B cell Expression e
mimicry
d antigens activation of Class II Imbalance
MHC
 Release of Sequestered Antigens

Release of myelin basic protein (MBP) in infection

Release of sperm Ag after vasectomy

Exposure of Eye lens protein after trauma

Exposure of heart muscle Ag after myocardial infarction

Molecular Mimicry
 Polyclonal B Cell Activation

Some viruses and

e.g. EBV, CMV -
bacteria non- These activated cells
stimulate anti-T, anti-B
specifically and secrete IgM which
reactivity and anti-
polyclonally activate B may lead to damage
nuclear antibodies etc
cells
Inappropriate Expression of Class II MHC:

Auto- In IDDM, b
antigens+MHC get cells from
presented to Th
cells by cells which
pancreas
do not normally express high
express high levels levels of
of MHC. Th cells
get activated and Class I and
may then activate Class II MHC
B, Tc and TDTH cells.
molecules
 Lymphokine Imbalance
Increased production of cytokines may result in
excessive T and B cell activation and subsequent
damage.

e.g. Increased IL-2 levels in SLE

 Signs of Autoimmune Disease
Elevated serum Various
gamma globulin
levels antibodies
Depressed Immune
levels of serum complexes in
complement the serum
Two Types of Autoimmune disease

Systemic/
Organ
Non-organ
Specificspecific
Two Types of Autoimmune disease

Organ Specific Non-organ specific

Essentially localized Widespread

Antigen throughout the body
to given organ

Antigen organ is Complexes deposit

Lesion target for (systematically particularly
immunologic attack in kidneys, skin and joints)

With other organ With other non-organ

Overlap specific antibodies specific antibodies
and diseases and diseases
Some autoimmune diseases in humans
 Spectrum of Autoimmune Diseases

Hashimoto’s thyroiditis
Organ Specific
Grave’s disease
Pernicious anemia
Addison’s disease
Type I Diabetes Mellitus
Myasthenia gravis
Multiple Sclerosis
Autoimmune hemolytic anemia
Idiopathic thrombocytopenic purpura
Goodpasture’s syndrome
Sjogren’s syndrome
Rheumatoid arthritis
Scleroderma
Systemic Systemic Lupus Erythematosus
Type II: Antibody-Mediated Diseases
 Type III:
Immune-
Complex
mediated
diseases

Type IV:
T Cell-
mediated
diseases