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ASPEK KLINIK PENYAKIT

AUTOIMUN
Dr. Safari Wahyu Jatmiko

GRAVES DISEASE

Graves' disease:
This is the most common cause of hyperthyroidism and is

due to TSH receptor antibodies (IgG) that bind to the


thyroid TSH receptor stimulating thyroid hormone
production, behaving like TSH.
These TSH receptor antibodies can be measured in
serum.
50% concordance is seen amongst monozygotic twins
with a 5% concordance rate in dizygotic twins.
the initiating event in the pathogenesis may be an
infection ' in a genetically susceptible individual,(as
Yersinia enterocolitica ,Escherichia coli and other Gramnegative organisms contain TSH binding sites), but the
precise initiating mechanisms remain unproven in most
cases.

PSORIASIS

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Psoriasis
T-cell mediated inflammatory dz
Epidermal hyperproliferation 2O to
activation of immune system
Altered maturation of skin
Inflammation
Vascular changes

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N
O
R
M
A
L

STRATUM
CORNEUM
STRATUM
GRANULOSUM

STRATUM
SPINOSUM

P Disorganized
S
O Neutrophil
R accumulation
I
A
S Immaturity
I
S Proliferation

STRATUM
BASALE

DERMIS

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Rheumatoid Arthritis
The prevalence of rheumatoid arthritis in most
Caucasian populations approaches 1% among
adults 18 and over and increases with age,
approaching 2% and 5% in men and women,
respectively, by age 65
The incidence also increases with age, peaking
between the 4th and 6th decades
The annual incidence for all adults has been
estimated at 67 per 100,000

Rheumatoid Arthritis
Both prevalence and incidence are 2-3 times
greater in women than in men
African Americans and native Japanese and
Chinese have a lower prevalence than Caucasians
Several North American Native tribes have a high
prevalence
Genetic factors have an important role in the
susceptibility to rheumatoid arthritis

Rheumatoid Arthritis
Rheumatoid arthritis is an autoimmune disease in
which the normal immune response is directed
against an individual's own tissue, including the
joints, tendons, and bones, resulting in
inflammation and destruction of these tissues
The cause of rheumatoid arthritis is not known
Investigating possibilities of a foreign antigen, such as a virus

Immunology

Macrophages:

Produce cytokines
Cytokines (TNF-) cause
systemic features
Release chemokines
recruit PMNs into synovial
fluid/membrane

Mediate disease processes


Activate B cells

B cells:

Release cytokines
Plasma cells that produce
Ab

TNF- & IL-1:

Proliferation of T cells
Activation of B cells
Initiates
proinflammatory/jointdamaging processes

TH-1 cells:

Osteoclasts:

Bone erosion
Juxta-articular & Systemic
osteoporosis

Pathophysiology

Swelling of Synovial lining


Angiogenesis

Rapid division/growth of cells = Pannus


Synovial thickening/hyperplasia
Inflammatory vascularized tissue
Generation of Metalloproteinases

Cytokine release

Infiltration of leukocytes
Change in cell-surface adhesion molecules & cytokines
Destruction of bone & cartilage

Rheumatoid Arthritis

Description
Morning stiffness
Arthritis of 3 or more
joints
Arthritis of hand joints
Symmetric arthritis
Rheumatoid nodules
Serum rheumatoid factor
Radiographic changes

A person shall be said


to have rheumatoid
arthritis if he or she has
satisfied 4 of 7 criteria,
with criteria 1-4 present
for at least 6 weeks

Diabetes Mellitus
Type 1 Diabetes

What is Diabetes?

Diabetes Mellitus the presence of elevated glucose levels in the blood due to
absolute or relative insufficiencies of insulin

171 million people suffer from diabetes


Type 1

Autoimmune destruction of the cells in the pancreas which are used to product insulin
1. Insulin administration
Type 2

Combination of defective insulin secretion and increased insulin resistance

Generally seen in overweight patients (85%)

Thought that obesity contributes to insulin resistance due to secretion of hormones


called adipokines that impairs glucose tolerance

Used to be seen in older patients, now disease is becoming more prevalent in children
as obesity grows among children
1. Life style change
2. Oral medications
i. Improve insulin production
ii. Regulate abnormal release of glucose by the liver
iii. Decrease insulin resistance
3. Insulin administration
Gestational diabetes

Insulin resistance caused by hormones during pregnancy

Usually improves or disappears after giving birth

Seen in 5% of pregnant women


1. Diet control

How do people get


diabetes?

Type 1
Genetic element/mutation, susceptibility to triggers:

Viral infections
Stress
Environmental exposure - exposure to certain chemicals or drugs

White blood cells, T lymphocytes, produce immune factors called cytokines


which attack and destroy cells of pancreas
Can take 7yrs. or longer to develop to absolute, by the time know something
is wrong 80% - 90% of cells are destroyed
10% chance of inheriting if first degree relative has diabetes
Most likely to inherit from father
Increase incidences would take at least 400 years if genetic factors were the
only cause
Viruses

Infection introduces a viral protein that resembles a cell protein


T-cells and antibodies tricked by this resemblance into attacking protein and virus

Cases rising in certain areas of U.S. particularly Northeastern region


Cows milk certain protein which may trigger attack on cells
Breast milk hormones which protect body from attack on cells
Type 2
Inheritance pattern, first degree relatives with type 2 have much higher risk
for developing
Perhaps inheriting a tendency towards obesity since 85% obese
Gestational
Genetically predisposed, have greater chance for developing type 2 later in

What are the Signs and


Symptoms?

Polyuria (frequent urination)

Glucose concentration in blood is high

Reabsorbtion of glucose in the proximal renal tubuli is


incomplete, glucose remains in urine

Osmotic pressure of urine increases

Inhibits reabsorbtion of water by kidney, resulting in


increase urine production
Dehydration

Lost water volume in kidney replaced from water held in


body, increased thirst and increased fluid intake polydipsia
Polyphagia

Increased appetite, no glucose delivered to muscles,


tissues, body sends signal to brain to eat something to
renourish
Weight loss and weakness

glucose cannot participate in crib cycle to be used as


energy, use of fat as alternative energy source
Vision changes

Importance of Control
Complications of Diabetes
Diabetic Ketoacidosis

Fat break down accelerates and increase the production of fatty acids

Fatty acids converted into ketone bodies

Ketones are toxic at high levels

Symptoms - rapid, deep breathing, polyuria, nausea, vomiting, abdominal pain,


altered states of mind such as hostility, mania, confusion, lethargy, and hypotension,
coma, death
Hypoglycemia

Low blood sugar, too much insulin or not enough glucose to cover insulin treatment

Symptoms - sympathetic activation of the autonomic nervous system: immobilized


panic, dread, agitated, sweaty, seizures
Amputations

Heal slowly

Fail to heal

Infection
Vascular diseases

Damage to blood vessels

Damage to arteries

Diabetic retinopathy growth of poor quality


new blood vessels in retina, retinal damage, blindness
Diabetic nephropathy damage to kidney,
chronic renal failure dialysis
Coronary artery disease, stroke, peripheral vascular,
diabetic myonecrosis (muscle wasting)

Diabetic foot neuropathy and arterial disease

Systemic Lupus
Erythematosus

Lupus

Systemic lupus
erythematosus (also called
SLE, or lupus) is an
autoimmune disease of the
body's connective tissues.
Autoimmune means that the
immune system attacks the
tissues of the body. In SLE,
the immune system primarily
attacks parts of the cell
nucleus.

SLE affects tissues throughout


the body. Five times as many
women as men get SLE. Most
people develop the disease
between the ages of 15 and
40, although it can show up at
any age.

Lupus = Autoimmunity
Systemic and affects connective tissue

Caused by malfunctions of:

T-cells
B-cells
Complement System
Signal Transduction

Can be lethal or not


Unique to each individual

Genetic Associations
HLAs are loci on genes that code for
certain chain on the MHC complex
HLA-DR2
HLA-DR3
HLA-DQB1 Involved in mediating
production of antibodies to ds-DNA

Main Pathology
The plasma cells are producing antibodies
that are specific for self proteins, namely
ds-DNA
Overactive B-cells
Suppressed regulatory function in T-cells
Lack of T-cells
Activation of the Complement system

Overactive B-cells
Estrogen is a stimulator of B-cell activity
Lupus is much more prevalent in females of
ages 15-45
Height of Estrogen production

IL-10, also a B-cell stimulator is in high


concentration in lupus patient serum.
High concentration linked to cell damage
caused by inflammation

T-cell Malfunctions
Fc region switch

Leads to malfunction in signaling and
decreased IL-2 production

Increased levels of Ca2+


Leads to spontaneous apoptosis

T-cell Signal Transduction

Activation of Complement System


Complement system is activated by
the binding of antibodies to foreign
debris.
In this case its over activation

RBCs lack CR1 receptor


Decreasing the affective removal of
complexes

IgG Pathogen
IgG is the most pathogenic
because it forms intermediate sized
complexes that can get to the small
places and block them.

LE Cell
The LE cell is a
neutrophil that has
engulfed the antibodycoated nucleus of
another neutrophil.
LE cells may appear in
rosettes where there
are several neutrophils
vying for an individual
complement covered
protein.

Overview of the pathogenesis of SLE


Infecti
on

UV
light
Self
Ag

External Ag

Skin cell

Genetic susceptibility

APC
T cell

T cell
IC

APC

Defective IC
clearance

B cell

A
b

Target

Symptoms
Non-specific:

Fatigue
Weight loss
Malaise = generally feeling ill
Fever
Anorexia (over time)
Arthritis
90% of patients experience arthritic symptoms
Symmetrical
Appears in hands, wrists, and knees mainly

Skin Manifestations
Malar or
Butterfly Rash
Discoid Rash
Stimulated by
UV light
Skin
manifestations
only appear in
30-40% of lupus
patients.

Renal (Kidney) Manifestations

50-70% of all lupus


patients experience
renal developments.
Most Dangerous:
Glomerulonephritis
where at least 50% of
the glomeruli have
cellular proliferation
Glomeruli capillary
beds in the kidney
that filter the blood.

Renal Failure because


of Glomerulonephritis
is the leading cause of
death among lupus
patients.

Normal

Glomerulonephritis

Other Manifestations
Cardiac
Central Nervous System
Hematological