AUTOIMMUNE

DISEASES
Hendra Tri Hartono
Anggie Muthmainnah
Firdaus Ramli
 AUTOIMMUNITY
Defined as the presence of immune response of antibody against self
antigen

Self antigens
Antigens that presents in ones own cells
Are altered by the action of bacteria, viruses, chemicals, or other drugs
Auto antibodies
antibody(a type of protein) produced by the immune system that is directed
against one or more of the individual's own proteins
 AUTOIMMUNE DISEASES
Requirements
The presence of autoimmune reaction
Evidence that such a reaction is not secondary to tissue damage (e.g. from
infection)
The absence of another well-defined cause of the disease

Result from tissue injury caused by T cells or antibodies that react against
self-antigens
Single organ organ specific disease (e.g. Type 1 DM)
Multiple organ generalized or systemic disease (e.g. SLE)
 MECHANISMS
1. Role of Susceptibility Genes
HLA genes
The presence of particular MHC alleles affects the negative selection of T
cells in the thymus or the development or regulatory T cells
Failure of self-tolerance
2. Role of Infections
Induction of costimulators on APCs self reactive antigens
Molecular mimicry
Microbes may express antigens that have the same amino acid sequences as self-
antigens self reactive antigens
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
 DEFINITION
Systemic lupus erythematosus (SLE) is a multi-system
auto-immune disease in which organs and cells undergo
damage, mediated by tissue binding autoantibodies
and immune complexes.
It is characterized by states of exacerbation and
remission
 EPIDEMIOLOGY
Occurs in 5 out of every 10,000 people
More frequent in Asian women than in Whites
Higher rates reported in Blacks
Highest in women aged 14-64 years
90% cases occur in women, mostly in the age of midwifery
 ETIOLOGY
1. FAMILIAL:
8% of affected patients have at least one first degree family member with SLE
For identical twins : 24% chances
For fraternal twins : 2% chance
2. GENETIC:
. 35 genes are known to increase risk for SLE
. Loci associated with SLE include TNF A1P3 & BANK 1
. Human leucocytic antigen (HLA):
HLA-A1, HLA-DR3 and HLA-88 are more common in patients with SLE
. Presence of null complement alleles
. Congenital abnormalities of complement (C2, C4) Associated with SLE risk
3. VIRUSES:
.EBV (Epstein-Barr Virus) causes T-cell abnormality failure in normal
immunoregulation of B-cell response (causes B cell hyperactivity)
4. ENVIRONMENT n MISCELLANEOUS CAUSES:
.Silica dust
.Cigarette smoking
.Estrogen administered to post-menopausal women increased SLE risk
.Decreased breast feeding
.Photosensitivity
.UV light stimulates KERATINOCYTES causes over-expression of nuclear
ribonucleoproteins (snRNPs) on their cell surface , and stimulates cytokine
secretion leading to Auto-antibody production
DIAGNOSIS
 COMMON LABORATORY
TESTS

Antinuclear Antibody (ANA)

Anti DNA
Anti-Sm
Anti-RNP
Anti-Ro
Anti-La
 FLUORESCENT ANA TEST
Nearly all SLE patients are ANA positive.

PATTERN ANTIGEN DISEASE

Peripheral dsDNA SLE
Speckled Acidic nuclear RA
protein
Ribonucleoprotein SLE
Extractable
nuclear antigen Scleroderma,
mixed connective
tissue disease
Homogenous dsDNA, ssDNA RA
Histones SLE, DI lupus
nucleolar Nucleolar RNA Progressive
systemic
sclerosis
 OTHER LABORATORY TESTS

CBC (RBC, WBC, platelets)

Urinalysis
Sedimentation Rate (ESR) Rheumatoid Factor
Skin biopsy
Kidney Biopsy
 EFFECT OF LABORATORY TESTS
WITH INCREASED LUPUS
ACTIVITY

h C reactive protein (CRP)

h Sedimentation rate (ESR)
h Anti DNA
i CBC (WBC, RBC,
h Liver and Kidney
Function tests platelets)
h CPK i Serum albumin
h Urine protein or cell casts
 COMMON
LUPUS MEDICATIONS

NSAIDs
Anti-malarials
Corticosteroids
Cytotoxic drugs
Investigational
(research)
 DRUG CLASS DRUG AND DOSE MAJOR INDICATIONS
NSAIDs Various agents Mild disease: fever, arthritis ,skin
Anti-inflammatory dose rash, serositis
Antimalarial Hydroxychloroquine, 200-400mg, PO daily Mild disease: arthritis, skin rash,
Chloroquine, 250-500mg, PO daily serositis

Corticosteroid Prednisone, 1-2mg/kg/d, PO daily (or Initial control of severe disease

equivalent) <1mg/kg/d (or equivalent) Control of mild disease or
maintenance after disease
Suppression with higher doses.
Life threatening disease
Methyl prednisolone, 500-600mg IV daily * 3-
6 days

Cytotoxic Cyclophosphamide, 0.5-1.0g/m2 IV monthly Most commonly used in severe lupus
for 6 months, then every 3 months for 2 years nephritis: may be necessary for
or 1 year after remission. other severe disease manifestations.
Azathioprine 1-3mg/kg PO daily
Cyclophosphamide,
1-3mg/kg PO daily
Mycophenolate mofetil, 1-3g PO daily
RHEUMATOID ARTHRITIS
 DEFINITION
Rheumatoid arthritis (RA) is a chronic, systemic
autoimmune disorder whose major distinctive feature is
chronic, symmetrical and erosive inflammation of the
synovial tissue of the joints.
The severity of the joint disease may fluctuate over time,
but progressive development of various degrees of joint
destruction, deformity and disability is the most common
outcome of established disease.
 INCIDENCE
About 1% of the worlds population is afflicted by
rheumatoid arthritis.
Onset is most frequent between the ages of 20 and 40,
but people of any age can be affected.
Women are three times more likely to get RA than men,
however women who are taking or have taken oral
contraceptives are less likely to develop RA.
 ETIOLOGY
Rheumatoid factor (RF), an
autoantibody directed against
immunoglobulin G (IgG)
Antibodies against collagen,
Epstein-Barr virus, encoded
nuclear antigen
Antikeratin antibody (AKA) & anti-
perinuclear factor (APF)
 RISK FACTORS
Genetic factors- People with RA are more likely to have a
gene called HLA- DR4, located on chromosome 6.
Environmental factors- Infectious agents that may induce
RA are mycoplasma organisms, Epstein-Barr virus, rubella
virus and Streptococcus. Smoking is also a major
environmental risk factor.
Hormonal factors- During pregnancy, women often
experience a symptom improvement of RA, due to increase
in estrogen and progesterone levels.
 PATHOPHYSIOLOGY
The pathologic process involved in RA are type
3( immune complex) and type 4( cell mediated)
reactions. If unarrested, pathologic changes in RA pass
through four stages:
1. Synovitis
2. Pannus formation
3. Fibrous ankylosis
4. Bony ankylosis
STAGE Presentation of antigen to T
1 cell
T and B cell proliferation

Activation of complement system

Activation of complex system &
release of lysosymes from
leukocytes
Proliferative inflammation
localized in joint capsule
Tissue thickens with
edema and congestion
SYNOVITIS
STAGE 2 PANNUS gradually
develops
Extends over the articular
surface into joint anterior
Adheres tightly to underlying
cartilage by invasion and lysis
Interferes with cartilage
nutrition
Pannus may extend over to
subchondral bone
Cartilage may become worn off
and become raw
 Subchondral bone
STAGE 3
erosion
Granulation tissue gets invaded
with tough fibrous tissue

Converted to scar tissue

Inhibits joint movements

Forms FIBROSIS ANKYLOSIS

STAGE Progress to bony ankylosis

4
 CLINICAL MANIFESTATIONS

1.Articular
Manifestations
2.Extra Articular
Manifestations
 ARTICULAR MANIFESTATIONS
Early stages
Active inflammation of joints
Hot, swollen and painful joints and
function may be decreased
Soft tissue deformity and
contractures due to prolonged
immobilization
Stiffness especially on first wakening
in the morning
 Later stages-
Deformity of hands and feet due to
misalignment resulting from swelling,
progressive joint destruction or partial
dislocation.
Muscle spasm and
weakness
 Others
Fever
Rheumatoid nodules at joint capsules
Fatigue
Weakness
Anorexia
Weight loss
Generalized aching
 DIAGNOSTIC TESTS
Radiologic examination-
This consists of X rays of both hands and of the affected joints. The
following features may be present:
Reduced joint space
Erosion articular margins
Subchondral cysts
Soft tissue swelling
 TREATMENT
Goal:
The induction of remission and its maintenance: the diseases activity is
brought under control by drugs.
The preservation of joint functions and prevention of deformities: during the
activity of disease and thereafter by physiotherapy and splinting.
Repair of the joint damage which already exists: it will relieve pain or
facilitate functions. It sometimes requires surgical interventions eg.
Synovectomy.
HIV - AIDS
 Acquired Immune Deficiency Syndrome (AIDS) is a type immune
suppression which cripples the human immune system and the ability of
the human body to resist infections diseases.
It is caused by the human immunodeficiency virus (HIV).
HIV is a type of retrovirus of an comprises of an envelope studded with
glycoprotein. This envelope surrounds a protein coat which contains the
viral genetic material
Two molecules of single-stranded RNA and an enzyme is
reversed transcriptase

The enzyme reversed transcriptase enables the virus to make DNA from its
RNA template, and thus earns its name as a retrovirus.
HIV destroys large portions of the T cells by using the glycoproteins in its
4

envelope to recognize and bind to receptor molecules (CD4) on the T cells

4

(host cells)
 During infection, HIV enters the body of a person and attaches to CD4
receptor on the membrane of the T cell and fuses with the plasma
4

membrane of these host cells.

The coat proteins are removed by enzymes and the RNA molecules and
reverse transcriptase of HIV enter the host cells.
Reversed transcriptase catalyzes the synthesis of a single DNA strand
complementary to the viral RNA strand. A second DNA strand
complementary to the first is then formed catalyzed by the same
enzyme.
The double-stranded complementary DNA (cDNA) is incorporated as a
provirus into the T cells chromosomal DNA, where it may lie dormant
4

for many years.

 The provirus is transcribed into RNA when the T4 cells become activated
as the body of the infected person responds to certain infection.
This Viral RNA serves as both messenger RNA for the formation of HIV
proteins and as genetic material for the new generations of viruses
formed.
Protein coats form around the viral RNA and reverse transcriptase
molecules to form new viruses.
 Viruses bub from the host cell, acquiring envelopes from the plasma
membrane of the host cell ? as they leave.
The new generations of viruses are released into the blood of the
infected person
This new population of HIV then attacks other T 4 cells, particularly those
in the lymph nodes.
As more and more of the T4 cells are destroyed, the immune system of
the infected person deteriorates, making that person susceptible to
various infections. This will eventually lead to death.
HIV also infects the brain cells of the infected person causing them to
be gradually damaged. The retrovirus also attacks the bone marrow and
causes the precursor cells in blood tissue to become a pool for HIV .
 SYMPTOMS
SYMPTOMS DESCRIPTION
1. No symptoms as a carrier During the initial stages of the infection, the
infected person does not show any symptoms
of the disease
(HIV STILL SPREADING)
2. (i) Fever These occur at the 2nd stage of the infection
(ii) Drastic loss of weight
(iii) cough
(iv) Fatigue
(v) Diarrhea
(vi) Candidiasis
(vii) Swollen lymph nodes
3. (i) Pneumonia These occur at the 3rd stage of the infection.
(ii) Kaposis sarcoma
(iii) Lymphoma
(iv) Mental disturbance
4. Death X_X Occurs within the next two years after the
infected person has develop full-blown AIDS
in five years.
 TRANSMISSION

HIV is found in the blood , semen or vaginal fluids of the

carrier.
Transmission can occur during blood transfer, transfer of
semen or vaginal from the carrier to person through the
following ways :-
(i) By having multiple sex partners who could be HIV carriers.
(ii) By sharing of needles or syringes with an HIV carrier.
(iii) Transfer of HIV by a mother who is a carrier to her fetus
through the placenta before birth.
(iv) Blood transfusions from a carrier the recipient.
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