Autoimmune Diseases

Introduction
• Central to the functioning of the immune system
is its ability to distinguish between invading or
foreign matter, which should be attacked, and
matter that is a normal part of the body, which
should not be attacked.
• Autoimmunity can be defined as breakdown of
mechanisms responsible for self tolerance and
induction of an immune response against
components of the self.
• In numerous autoimmune diseases it is well
recognized that products of the immune system
cause damage to the self.
 Auto Immunity
• Auto or Self antigens
– Antigens present in ones own cells
– Altered by the action of bacteria, viruses, chemicals or drugs as
a non-self
• Auto antibody
– Altered cell (Auto Ag) - elicits the productions of Antibody
• Auto Immunity
– Immune response of auto Ab against self Ag
– Humoral or cell mediated immune response against the
constituents of the body’s own tissues.
– There are more than 80 different kinds of diseases caused by
autoimmunity.
 Autoimmune Diseases
– Autoimmune diseases is a group of disorders in which
tissue injury is caused by humoral (by auto-antibodies)
auto-antibodies or
cell mediated immune response (by auto-reactive T cells)
cells
to self antigens.
• Normally, the immune system does not attack the
self.
self This is ensured by elimination of auto-reactive
lymphocytes during their development (negative
selection).
• However, there is a large group of autoimmune
diseases in which the immune system attacks self-cells
• The attack can be directed either against a very
specific tissue or to a large number of tissues
• Once started, autoimmune diseases are hard to stop
 Causes of Autoimmune Diseases
1. Sequestered or Hidden antigens
• Some antigens in the body are hidden from
cells of the immune system. If there is damage
to these organs causing exposure of these
sequestered antigens an immune reaction to
these antigens may occur. E.g. Lens Ag, Sperm
Ag.
2. Infection & mimicry: Changes in self-antigens, that
make them look like non-self to the immune system, due to:
– Viral or bacterial infection
– Irradiation
– Medication
– Smoking
 Rheumatic
fever is a
classic example
of molecular
mimicry

•A foreign Ag which resembles a

self Ag
•Streptococcal M protein & Heart
muscles, Nephritogenic strains of
Streptococci Ags & Renal glomeruli
share similar epitopes.
Pathogens
 Causes of Autoimmune Diseases
3. Age
• It may result when tolerance to the self-Ag is
lost.
• AID are more prevalent in older people and
animals.
• This is due to immunosenescence as well as
diminishing immuno regulatory mechanisms.
 Causes of Autoimmune Diseases
4. Drugs
• Certain drugs initiate AID by unknown mechanisms
• –Examples: Procainamide (Pronestyl)
• Used to treat Ventricular arrythmia
• –Drug induced lupus
5. Genetics - possession of certain MHC alleles.
• Familial inheritance
• Mutation in the genes responsible for HLA
expression, genes related with lymphocyte
activation, lymphocyte suppression are likely to play
crucial role.
 Genetic Influence

• It is well recognized that certain immune

disorders predominate in females and in
families.
• Determined by family studies.
• Genetic links have occurred between diseases
and HLA antigens
6. Hormones (male vs female)

•Females are much more likely to develop autoimmune

illness
•Rise in hormones associated with pregnancy may even
cause abortion of the fetus (RSA)
Endometriosis and preeclampsia are both thought to be
autoimmune in nature. Women are 2.7 times more
susceptible as compared to men.
–SLE, Grave’s disease : Female are more susceptible
–Ankylosing Spondilitis : Male specific
7. Immunodeficiency
•Deficiency of complement components like C2,C4,C5,C8
•CVID : Common Variable Immuno Deficiency (auto
antibodies against platelets)

8. Environment
Pathogens, drugs, hormones, and toxins are just a few
ways that the environment can trigger autoimmunity.
Examples: Toxic Oil Syndrome
–Occurred in Spain in 1981 after people ate contaminated
olive oil.
–People developed unique illness marked by lung disease,
eosinophilia, and excessive IgE
 Complement Deficiencies
• CD59 or CD55 –
–Paroxysmal nocturnal
hemoglobinuria
–autoimmune hemolytic anemia
–autoimmune thrombocytopenia
–lupus lymphopenia

• Deficiencies in the classical

complement pathway renders
individuals more likely to
develop immune complex
diseases
–SLE
–RA
 RISK FACTORS
➢ Genetic factor
➢ Environmental toxins
➢ Gender
➢ Heredity
➢ viruses
➢ Drugs
➢ Stress
➢ Poor diet
➢ Lack of exercise
➢ Lack of sleep
➢ Abuse of alcohol and use of tobacco
 Development of
Autoimmune Disease
• Autoimmune disease occurs as a result of breakdown in
tolerance to self
• Autoimmune disease is characterized by immune system
“attack” against self antigens that lead to tissue damage
– Inflammation and hypersensitivity reactions
• Mediated by B-lymphocytes that produce antibodies to self
antigens
And / or
• T-lymphocytes with T-cell receptors that recognize self
antigens
– Autoreactive CD4 Th and autoreactive CD8 cytotoxic T cells
 Common Autoimmune Diseases
Affects…
Name adrenal cortex
Addison's disease Ankylosing spondylitis spine and sacroiliac joints
Antiphospholipid antibody syndrome veins and/or arteries.
(APS) Aplastic anemia bone marrow
Diabetes mellitus type 1 insulin-producing beta
Goodpasture's syndrome Graves' disease cells
Guillain-Barré syndrome (GBS) kidneys and lungs
Hashimoto's disease hyperthyroidism
Idiopathic thrombocytopenic purpura peripheral nervous system
Lupus erythematosus hypothyroidism
Multiple sclerosis Rheumatoid arthritis platelets All tissue
Sjögren's syndrome central nervous system
bone joints
exocrine glands
 SPECTRUM AND PREVALENCE
• Spectrum of Auto Immune Diseases
• Prevalence of Auto Immune Diseases
 Spectrum of Auto Immune Diseases

• Blood and blood vessels

• Autoimmune hemolytic anemia
• Pernicious anemia
• Polyarteritis nodosa
• Systemic lupus erythematosus
• Wegener’s granulomatosis
 Spectrum of Auto Immune Diseases

• Digestive tract (including the mouth)

• Autoimmune hepatitis
• Behçet’s disease
• Crohn’s disease
• Primary bilary cirrhosis
• Scleroderma
• Ulcerative colitis
 Spectrum of Auto Immune Diseases

• Heart
• Myocarditis
• Rheumatic fever
• Scleroderma
• Systemic lupus erythematosus
 Spectrum of Auto Immune Diseases

• Eyes
• Sjögren’s syndrome
• Type 1 diabetes mellitus
• Uveitis
 Spectrum of Auto Immune Diseases

• Glands
• Graves’ disease
• Thyroiditis
• Type 1 diabetes mellitus
 Spectrum of Auto Immune Diseases

• Joints
• Ankylosing spondylitis
• Rheumatoid arthritis
• Systemic lupus erythematosus
 Spectrum of Auto Immune Diseases

• Kidneys
• Glomerulonephritis
• Systemic lupus erythematosus
• Type 1 diabetes mellitus
 Spectrum of Auto Immune Diseases

• Lungs
• Rheumatoid arthritis
• Sarcoidosis
• Scleroderma
• Systemic lupus erythematosus
 Spectrum of Auto Immune Diseases

• Muscles
• Dermatomyositis
• Myasthenia gravis
• Polymyositis
 Spectrum of Auto Immune Diseases

• Nerves and brain

• Guillain-Barré syndrome
• Multiple sclerosis
• Systemic lupus erythematosus
 Spectrum of Auto Immune Diseases

• Skin
• Alopecia areata
• Pemphigus/pemphigoid
• Psoriasis
• Scleroderma
• Systemic lupus erythematosus
• Vitiligo
 Spectrum of AID
Autoimmunity can affect ANY organ/organ system in the human body

Autoimmune Uveitis Multiple Sclerosis

Sjogren’s Syndrome
Pemphigus

Rheumatic Fever Goodpasture’s Syndrome

Diabetes
Autoimmune Hepatitis
Addison’s Disease

Autoimmune Oophoritis Ulcerative Colitis

Rheumatoid Arthritis
Autoimmune hemolytic Anemia
 Prevalence
• Autoimmune diseases are a major
threat to the health of everybody.
• 3.5 % individuals are affected.
• Women are 2.7 times more
susceptible as compared to men.
• SLE prevalence- Female : Male =
10:1
 Examples of Organ Specific
Lungs of a patient
with
Goodpasture’s

Hashimoto’s disease
(thyroiditis) Vitiligo
 Classification of Autoimmune Diseases
• Broadly classified into 3 groups
1. Haemolytic autoimmune diseases
2. Localised
3. Systemic autoimmune diseases

1. Haemolytic autoimmune diseases

- Clinical disorder due to destructions of blood
components. Auto Ab are formed against one’s own
RBCs, Platelets or Leucocytes.
- E.g. Haemolytic anaemia, Leucopenia,
Thrombocytopenia,
Thrombocytopenia etc.
 Classification of Autoimmune Diseases
2. Localised autoimmune diseases or
Organ specific autoimmune diseases
- A particular organ is affected due to auto Abs.
- For example:
– Thyroiditis (attacks the thyroid)
– Multiple sclerosis (attacks myelin coating of nerve
axons)
– Myasthenia gravis (attacks nerve-muscle junction)
– Juvenile diabetes or Type I DM (attacks insulin-
producing cells)
Classification of Autoimmune Diseases
3. Systemic autoimmune diseases or
Non-organ specific autoimmune diseases
• Immune complexes accumulate in many tissues and cause
inflammation and damage.
• Affects many organs or the whole body

- For example:
– Systemic Lupus Erythematosus (anti-nuclear Ab.): Harms
kidneys, heart, brain, lungs, skin…
– Rheumatoid Arthritis (anti-IgG antibodies): Joints,
hearts, lungs, nervous system…
– Rheumatic fever:
fever cross-reaction between antibodies to
streptococcus and auto-antibodies.
 Three types of autoimmune
disorders

– Cytotoxic (Type II hypersensitivity reactions)

– Immune complex (Type III hypersensitivity
reactions)
– Cell-mediated (Type IV hypersensitivity
reactions)
 TYPES OF HYPERSENSITIVITY
• Type II
– Autoimmune hemolytic anaemias
- Myasthenia gravis
- Goodpasture’s syndrome
• Type III
– Systemic lupus erythematosus (SLE)
– Rheumatoid arthritis
• Type IV
Anti-insulin receptor antibody (insulin-dependent
diabetes mellitus )
 Autoimmune Haemolytic anemia
• Lysis of RBC is due to the production of autoantibodies
against the RBC-antigens.
• RBC half life= 21 days, for haemolytic anaemia,
anaemia<7days
• Caused by reactions to infections or drug therapy
[Penicillin, anti-hypertensive agent like methyldopa
results in destruction of RBCs]
• This is an antibody mediated autoimmune disease.
• 2 classes of autoantibodies involved are
• IgM or Cold Agglutins- active at 40 C but not at 370C.
• IgG or Warm Agglutins - active at 370 C but not at
40C.
 Thrombocytopenia
• Characterized by low platelet count due to the
production of antiplatelet Ab. (IgG type)
Mechanism:
• Antibody mediated autoimmune disease.

• An interaction of Ab with bound drug or new Ag.

causes intravascular agglutination of platelets & can
be eliminated by phagocytic cells.
 Myasthenia Gravis

• Persons with myasthenia gravis make an

antibody that blocks the transmission of nerve
impulses to muscle; this causes the muscle
weakness and breathing difficulty associated
with the disease.
• It is a neuromuscular disease characterized by
varying degrees of weakness of the skeletal
(voluntary) muscles of the body.
 Symptoms
• Facial weakness,
• Difficulty chewing and swallowing,
• Inability to maintain support of trunk, neck or
head.
 Goodpasture’s Syndrome

• An uncommon and life-threatening

hypersensitivity disorder is characterized by renal
(kidney) disease and lung hemorrhage.
• Antibodies react with antigens in the glomerular
basement membrane of the kidney, results in
severe necrosis.
• Antigen in kidney is similar to antigen found in
lungs, resulting in antibody reacting with lung
tissue resulting in pulmonary hemorrhage.
•
 Symptoms
• Symptoms include:
– foamy,
– bloody, or dark colored urine,
– decreased urine output,
– cough with bloody sputum,
– difficulty breathing after exertion,
– weakness,
– fatigue,
– nausea or vomiting,
– weight loss,
– nonspecific chest pain
– and/or pale skin
 Systemic Lupus Erythematosus
• Chronic, systemic inflammatory disease caused by
immune complex formation.
• The word "systemic" means the disease can affect
many parts of the body.
• Associated with immune complexes deposited in
tissues resulting in inflammation.
• Parts of the body affected include: the joints, skin,
kidneys, heart, lungs, blood vessels, and brain.
• Found more frequently in women.
• Has both genetic and environmental factors.
 SLE
• Auto-antibodies formed against a variety of self
antigens
• Anti-double stranded DNA,RNA and histones
• Antibodies against cell surface antigens on RBC’s
and/or platelets
• Tissue damage caused by Type III hypersensitivity
reactions
 SLE Clinical Signs
• Extremely diverse and nonspecific.
• Joint involvement most frequent sign:
polyarthralgia and arthritis occur in 90% of
patients.
• Skin manifestations next most common.
• Erythematosus rash may appear.
• Most classic is butterfly rash.
 SLE Butterfly Rash
• The characteristic
butterfly-shaped
rash of the disease
classically is found
across the nose and
cheeks.
Butterfly Rash (SLE)
 SLE Clinical Signs
• Renal involvement very common.
– Caused by deposition of immune complexes in
kidney tissue.
– Leads to renal failure, most common cause of
death.
• Other systemic effects:
– Cardiac
– Central nervous system.
– Hematologic abnormalities.
 Treatment

• Aspirin and anti-inflammatories for fever and

arthritis.
• Skin manifestations-topical steroids.
• Systemic corticosteroids for acute fulminant
lupus, lupus nephritis or central nervous
system complications.
• Five year survival rate is 80 to 90%.
 Rheumatoid Arthritis

• Chronic inflammatory disease primarily affecting the

joints, but can affect heart, lung and blood vessels.
• Caused by the auto Antibody of IgM type, called
rhematoid factors.
• Women three times more likely as men to have it.
• Typically strikes at ages between 20 and 40, but can
occur at any age.
• The three major symptoms of arthritis are joint
pain, inflammation, and stiffness.
 Clinical Signs
• Symptoms initially non-specific: malaise, fever,
weight loss, and transient joint pain.
– Morning stiffness and joint pain improve during the day.
– Symmetric joint pain: knees, hips, elbows, shoulders.
– Joint pain leads to muscle spasm, limits range of motion,
results in deformity.
• Certain bacteria may trigger RA due to certain
proteins that possess antigens similar to those
antigens found in joint, i.e., molecular mimicry
Rheumatoid Arthritis

Figure 43.21
 Immunologic Findings
• Rheumatoid Factor (RF) is an IgM antibody
directed against the Fc portion of the IgG
molecule, it is an anti-antibody.
• Immune complexes form and activate
complement and the inflammatory response.
• Enzymatic destruction of cartilage is followed
by abnormal growth of synovial cells, results
in the formation of a pannus layer.
Rheumatoid Arthritis
 Hashimoto's Thyroiditis
• Hashimoto's Thyroiditis is a type of autoimmune
thyroid disease in which the immune system attacks
and destroys the thyroid gland.
• The thyroid helps set the rate of metabolism - the
rate at which the body uses energy.
• Hashimoto’s prevents the gland from producing
enough thyroid hormones for the body to work
correctly.
 Hashimoto’s Thyroiditis

• Organ specific disease affecting the thyroid gland.

• Most often seen in women 30 to 40 years old,
may be genetic predisposition.
• Common cause of hypothyroidism.
• Causes diffuse hyperplasia in the gland resulting
in development of a goiter.
• Thyroid autoantibodies are formed.
• Hashimoto's thyroiditis occurs eight times more
often in women than men.
 Symptoms
• The following are the most common symptoms.
– goiter (enlarged thyroid gland which may cause a bulge in
the neck)
– other endocrine disorders such as diabetes, an
underactive adrenal gland, underactive parathyroid
glands, and other autoimmune disorders
– fatigue
– muscle weakness
– weight gain
 Thyroid
• Thyroid hormones are produced by the thyroid gland. This
gland is located in the lower part of the neck, below the
Adam's apple.
• The gland wraps around the windpipe (trachea) and has a
shape that is similar to a butterfly - formed by two wings
(lobes) and attached by a middle part (isthmus).
 Goiter

• This enlargement is due to the inflammatory cells which

destroy thyroid cells, resulting in long term scarring. When
the cells are damaged they cease thyroid hormone
production, resulting in hypothyroidism
• A goiter only needs to be treated if it is causing symptoms.
• The enlarged thyroid can be treated with radioactive iodine to
shrink the gland or with surgical removal of part or all of the
gland (thyroidectomy).
• Small doses of iodine (Lugol's or potassium iodine solution)
may help when the goiter is due to iodine deficiency.
 Treatment
• Thyroid hormone replacement.
• Spontaneous remissions have occurred.
 Insulin Dependent Diabetes Mellitus

• Autoimmune process causes destruction of cells in the

pancreas resulting in insufficient insulin production
and an increase of sugar in the blood. This leads to
marked thirst and increased urine production. After
many years of diabetes, blindness, kidney failure, or
other severe or fatal complications often occur.

• Occurs before age 20

• Inherited susceptibility.
• Environmental influences including viral infections.
 Complications

• With its complications, diabetes is the seventh

leading cause of death in the United States.
• Diabetes is the leading cause of new blindness in
people 20-74 years of age.
• Ten to twenty-one percent of all people with
diabetes develop kidney disease.
• People with diabetes are 2-4 times more likely to
have heart disease.
• About 60%-70% of people with diabetes have mild to
severe forms of diabetic nerve damage, which, in
severe forms, can lead to lower limb amputations.
 Treatment
• Injected insulin.
• Immunosuppressive drugs for newly
diagnosed patients.
 Multiple Sclerosis

• Multiple sclerosis (MS) is a chronic, potentially debilitating

disease that affects the brain and spinal cord (central nervous
system).
• Destruction of myelin sheath of axons results in formation of
lesions (plaques) in white matter of brain and spinal cord.
• Causes inflammation and injury to the sheath and ultimately
to the nerves.
• The result may be multiple areas of scarring (sclerosis).
• Cause may include genetic and environmental factors.
• Most often seen between ages of 20 and 50.
 Multiple Sclerosis
• Because the myelin is damaged, messages moving
along the nerve are transmitted more slowly or not
at all which slows or blocks muscle coordination,
visual sensation and other nerve signals.
 Diagnosis of Auto immune disease
• Medical History
• Diagnosed by clinical symptoms and physical
examination
• Confirmed by detecting the auto Ab in the serum of
the patients.
• Autoantibodies are demonstrated by
immunoflurescent Ab test, haemagglutination,
Complement fixation, immunodiffusion, Radio
immuno assay, etc.
 Treatment
• Some autoimmune diseases are treated with medications
that alleviate specific symptoms.

• Haemolytic anaemia: Treated with Vit B12

• Myasthenia Gravis: Treated with Choline estrase
inhibitors
• Rhemotoid Arthritis: Anti-inflammatory drugs
• Lupus Erythematosus: Treated with immunosuppresive or
antimitiotic drugs such as Corticosteroid,
Cyclophosphamide and azothioprine.
 Treatment Options
• Anti-inflammatory drugs
•NSAIDS, Corticosteroids
• Immunosuppressant drugs
•Methotrexate
• Radiation
• Plamapheresis
• Cell Blocking Reagents
• aCD20 (Rituxan)
• aCD3 (Teplizumab)
• Cytokine Blocking Reagents
•TNF (Humira, Enbrel)
 Treatment
• Treatment usually entails therapy with
steroids, which suppress the immune system.
In some autoimmune diseases, especially
organ-specific ones, replacement therapy is
used; for example, insulin is given to diabetic
patients or thyroid hormone is administered
in autoimmune thyroid diseases.
 Summary
• Autoimmune diseases and conditions exist when
the body produces abnormal cells, which attack
the body, itself
• Most autoimmune diseases affect women more
often than men
• The causes of autoimmune diseases are not
known but some autoimmune diseases seem to
run in families
• May affect any part of the body, symptoms vary
widely and diagnosis and treatment are often
difficult
• Medical science is striving to design therapies
that prevent autoimmune diseases