Auto Immunity

Autoimmunity
Mehul P. Dave Archana S. Rana

Dysfunctional Immunity
–Hypersensitivity
–Autoimmunity
–Immunodeficiency

Autoimmunity
• Basically means immunity to self
• A condition that occurs when the
immune system mistakenly attacks
and destroys healthy body tissue.

• Self Tolerance and Tolerogens
• Normally Prevention or Dampening of AIR
occurs by…
– Immunosuppression by cells or cytokines
– Immunosuppression by hormones
– Deletion of auto immune T or B Cells
Autoimmunity

Autoimmune Disease
• Self tolerance is lost
• Specific adaptive immune responses
mounted against self antigens
• Inability to eliminate antigen leads to
chronic inflammatory process
• 3.5 % individuals are affected by AID

Autoimmunity Origins
Horror autotoxicus …
Literally meaning : The horror
of self toxicity
A term coined by the German
immunologist Paul Ehrlich (1854-
1915) to describe the threat of
AutoImmunity

This concept of autoimmunity as the
cause of human illness is relatively
new, and it was not accepted into the
mainstream of medical thinking until
the 1950s and 1960s.

• Paul Ehrlich, at the beginning of the
twentieth century, proposed the
concept of horror autotoxicus, where
in a 'normal' body does not mount
an immune response against its own
tissues.
• Thus, any autoimmune response was
perceived to be abnormal and
postulated to be connected with
human disease.

Common Autoimmune Diseases
Name Affects…
Addison's disease adrenal cortex
Ankylosing spondylitis spine and sacroiliac joints
Antiphospholipid antibody syndrome (APS) veins and/or arteries.
Aplastic anemia bone marrow
Diabetes mellitus type 1 insulin-producing beta cells
Goodpasture's syndrome kidneys and lungs
Graves' disease hyperthyroidism
Guillain-Barré syndrome (GBS) peripheral nervous system
Hashimoto's disease hypothyroidism
Idiopathic thrombocytopenic purpura platelets
Lupus erythematosus All tissue
Multiple sclerosis central nervous system
Rheumatoid arthritis bone joints
Sjögren's syndrome 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

• Digestive tract (including the mouth)
• Autoimmune hepatitis
• Behçet’s disease
• Crohn’s disease
• Primary bilary cirrhosis
• Scleroderma
• Ulcerative colitis

• Heart
• Myocarditis
• Rheumatic fever
• Scleroderma

• Eyes
• Sjögren’s syndrome
• Type 1 diabetes mellitus
• Uveitis

• Glands
• Graves’ disease
• Thyroiditis

• Joints
• Ankylosing spondylitis
• Rheumatoid arthritis

• Kidneys
• Glomerulonephritis

• Lungs
• Rheumatoid arthritis
• Sarcoidosis
• Scleroderma

• Muscles
• Dermatomyositis
• Myasthenia gravis
• Polymyositis

• Nerves and brain
• Guillain-Barré syndrome
• Multiple sclerosis

• Skin
• Alopecia areata
• Pemphigus/pemphigoid
• Psoriasis
• Scleroderma
• Vitiligo

Spectrum of AID
Autoimmunity can affect ANY organ/organ system in the human body
Pemphigus
Multiple Sclerosis
Sjogren’s Syndrome
Rheumatic Fever
Autoimmune Hepatitis
Ulcerative Colitis
Goodpasture’s Syndrome
Diabetes
Autoimmune Uveitis
Autoimmune hemolytic Anemia
Addison’s Disease
Rheumatoid Arthritis
Autoimmune Oophoritis

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
Vitiligo
Hashimoto’s disease
(thyroiditis)

Examples of Systemic Autoimmunity
SLE

Examples of Systemic Autoimmunity
Sjogren’s Syndrome

Factors contributing to the
Development of Autoimmunity
• Autoimmunity is multi factorial

–Women are 2.7 times more susceptible
as compared to men.
–SLE, Grave’s disease : Female are more
susceptible
–Ankylosing Spondilitis : Male specific
Gender

Gender
Female mice (SLE)
Removal of ovary Prevention
of SLE
Injection of testosterone

Age
• AID are more prevalent in older people
and animals.
• This is due to immunosenescence as well
as diminishing immuno regulatory
mechanisms.

Genetic factors
• Familial inheritance
• Mutation in the genes responsible for
HLA expression, genes related with
lymphocyte activation, lymphocyte
suppression are likely to play crucial role.
• Complement deficiency also plays a role
in the development of AID.

Infections
–EBV (Epstein Barr Virus)
–Mycoplasma
–Streptococci ANTIGENIC
–Klebsiella MIMICRY
–Malaria
–Borrelia

Chemical Nature of Auto antigens
• Target antigens for autoimmune response…
– Cell surface proteins
– Cytoplasmic molecules
– Nucleare molecules
– Secreted molecules
– HSPs
– Enzymes

Drugs
• Drugs : Certain drugs initiate AIR by
unknown mechanisms
–Examples: Procainamide (Pronestyl)
•Used to treat Ventricular arrythmia
–Drug induced lupus

Toxins
–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

Hormones
• 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

Immunodeficiency
• Deficiency of complement components like
C2,C4,C5,C8
• CVID : Common Variable Immuno Deficiency
(auto antibodies against platelets)

Environment
• Pathogens, drugs, hormones, and toxins
are just a few ways that the environment
can trigger autoimmunity

Mechanisms of Development
• Breakdown of self tolerance
• Molecular mimicry
• T cell by pass
• Defective regulation by Th
• Polyclonal activation
• Modification of cell surfaces by microbes
• Modification of cell surfaces by drugs
• Availability of sequestered self antigens
• Dysregulation of Idiotype Network

Rheumatic
fever is a
classic example
of molecular
mimicry

Nature Immunology 2, 777 - 780 (2001)
Gender
differences in
autoimmunity

Complement Deficiencies
• CD59 or CD55 –
– Paroxysmal nocturnal
hemoglobinuria
– autoimmune hemolytic anemia
– autoimmune thrombocytopenia
– lupus lymphopenia
• Deficiencies in the classical
complement pathway renders
pts more likely to develop
immune complex diseases
– SLE
– RA

RISK FACTORS
Genetic factor ,
Environmental toxins,
Gender,
Heredity,
viruses,

RISK FACTORS
Drugs,
Stress,
Poor diet,
Lack of exercise,
Lack of sleep,
Abuse of alcohol and use of tobacco.

Diagnosis of Autoimmune Diseases
• Autoimmune diseases often don’t show a
clear pattern of symptoms at first. So
diagnosing them can be hard. But with time, a
diagnosis can usually be made by using
following approaches :

• Medical history—The doctor will ask about
your symptoms and how long you have had
them. Your symptoms may not point to one
disease. But they can be a starting point for
your doctor. You should tell your doctor if
you have a family member with autoimmune
disease. You may not have the same disease
as your family member. But having a family
history of any autoimmune disease makes
you more likely to have one.

• Physical exam—During the exam, the doctor will
check for any signs. Inflamed joints, swollen
lymph nodes, or discolored skin might give
clues.
• Medical tests—No one test will show that you
have an autoimmune disease. But doctors may
find clues in a blood sample. For example,
people with lupus or rheumatoid arthritis often
have certain autoantibodies in their blood.
Autoantibodies are blood proteins formed
against the body’s own parts.

• Not all people with these diseases have these
autoantibodies. And some people without
autoimmune disease do have them. So blood tests
alone may not always help. But if a person has disease
symptoms and autoantibodies, the doctor can be more
sure of a diagnosis.
• The key is patience. Your doctor may be able to
diagnose your condition quickly based on your history,
exam, and test results. But the process often takes
time. It may take several visits to find out exactly
what’s wrong and the best way to treat it.

Treatment of Autoimmune Diseases
• Autoimmunity takes many forms. There are
also many treatments for it. Treatment
depends on the type of disease, how severe it
is, and its symptoms. Generally, treatments
have one of three goals:

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)

• Relieving symptoms—If your symptoms
bother you, your doctor may suggest
treatments that give some relief. Relieving
symptoms may be as simple as taking a drug
for pain relief. It may also be as involved as
having surgery.

• Preserving organ function—When
autoimmune diseases threaten organs,
treatment may be needed to prevent
damage. Such treatments may include drugs
to control an inflamed kidney in people with
lupus. Insulin injections can regulate blood
sugar in people with diabetes. These
treatments don’t stop the disease. But they
can save organ function. They can also help
people live with disease complications.

• Targeting disease mechanisms—Some drugs
may also be used to target how the disease
works. In other words, they can suppress the
immune system. These drugs include
cyclophosphamide (Cytoxan*) and
cyclosporine (Neoral and Sandimmune). The
same immune-suppressing drug may be used
for many diseases.

• The doctor may not prescribe a treatment. If
the symptoms are mild, the risks of treatment
may be worse than the symptoms.
• One may choose to put off treatment for now.
But one should watch for signs that the
disease is progressing. Visit the doctor
regularly. It is needed to catch changes before
they lead to serious damage.

Vocabulary
• anergy: a state of non-responsiveness to antigen
• antibody: an antigen-binding immunoglobulin, produced by
B-ells, that functions as the effector of an immune response
• antigen: a foreign molecule that does not belong to the host
organism and that elicits an immune response
• B-cell: a type of lymphocyte that develops in the bone
marrow and later produces antibodies, which mediate
humoral immunity
• central tolerance: when auto-reactive B-cell in the bone
marrow and auto-reactive T-cells in the thymus are eliminated

humoral immunity: the type of immunity that fights bacteria and
viruses in the body fluids with antibodies that circulate in blood
plasma and lymph
immune system: is the name used to describe the totality of the
host defence mechanism
lymphocyte: a class of white blood cells; two main classes: B-cells
and T-cells, which mediate humoral and cell-mediated immunity,
respectively.
peripheral tolerance: is tolerance acquired by mature lymphocytes
in the peripheral tissue
plasma cell: a derivative of B-cells that secretes antibodies, i.e.
antibody factory
T-cell: a type of lymphocyte that develops in the thymus

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