Autoimmunity - Microbiology - Immunology - Dr.Someshwaran Rajamani December 2015
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Transcript of Autoimmunity - Microbiology - Immunology - Dr.Someshwaran Rajamani December 2015
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AUTOIMMUNITY
Dr. R. Someshwaran, MBBS, MD., Assistant professor, Department of Microbiology,
Karpagam Faculty of Medical Sciences and Research, Othakalmandapam, Coimbatore-641032
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Objectives• Define Autoimmune disease• Classify them• Aid in Diagnosis
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Introduction
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Introduction
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Introduction
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Molecular mimicry
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Balanced immune system
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ETIOLOGY OF AID
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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 (misnomer, alternative= auto allergy)• Immune response of auto Ab against self Ag• Humoral or cell mediated immune response against the constitute’s of the
body’s own tissues.• There are more than 80 different kinds of diseases caused by autoimmunity.
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Definition• Condition in which structural or functional damage is produced
by the action of immunologically competent cells or antibodies
against the normal components of the body.
• Protection against self – injury to self
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Characteristic Features• Elevated levels of immunoglobulins
• Demonstrable autoantibodies
• Deposition of immunoglobulins on specific sites• Accumulation of lymphocytes and plasma cells - lesion
• Benefit from corticosteroid / immunosuppressants• Occurrence of more than one one type of autoimmune lesion
• Genetic predisposition
• Higher incidence in females’
• Chronicity / non reversible
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Tolerence• Ability to recognize self antigens
• Develops when T and B cells mature from precursor cells
• During maturation, cells which bind to self antigens – eliminated
• Population which does not react with self molecules survive
• “immunological unresponsiveness to self antigens”
• Tolerence to self antigens break down - autoimmunity
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Causes: • Happens when the immune system can't tell the difference between
healthy body tissue and antigens. Immune response will destroys normal body tissues. This response is a hypersensitivity reaction similar to the response in allergic conditions.• In allergies, the immune system reacts to an outside substance.• Under normal circumstances immune system will not destroy self
antigens.• In numerous autoimmune diseases it is well recognized that
products of the immune system cause damage to the self. • With autoimmune disorders, the immune system reacts to normal
body tissues.
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An autoimmune disorder may result in:
• The destruction of one or more types of body tissue
• Abnormal growth of an organ
• Changes in organ function
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Organs and tissues commonly affected by autoimmune disorders include:
• Blood vessels & Connective tissues• Endocrine glands such as the thyroid or pancreas• Joints; Muscles• Red blood cells• Skin
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Autoimmunity
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Contributing Factors• Defects in the immune system.• Influence of hormones• Environmental conditions
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Autoimmune Diseases• Autoimmune diseases is a group of disorders in which tissue injury is caused
by humoral (by auto-antibodies) or cell mediated immune response (by auto-reactive T cells) to self antigens.
• Normally, the immune system does not attack the self. However, there is a large group of autoimmune diseases in which the immune system does attack self-cells• The attack can be directed either against a very specific tissue
or to a large no. of tissues• Once started, autoimmune diseases are hard to stop
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Causes of Autoimmune Diseases
1. Sequestered or Hidden antigens• Ag in the secluded places - are not accessible to the immune system.• E.g. Lens Ag, Sperm Ag & Thyroglubulin.2. Neo antigens• Altered or Modified Antigens – by physical (irradiation), chemical
(drugs) or microbial agents ( intracellular viruses)3. Cessation of Tolerance• It may result when tolerance to the self-Ag is abrogated.
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Causes of Autoimmune Diseases
4. Cross reacting Antigens• A foreign Ag which resembles self a 2nd Ag• Many species share organ specific Ags.• E.g. Ag of Human brain & Ag of sheep brain, Streptococcal M
protein & Heart muscles, Nephritogenic strains of Streptococci Ags & Renal glomeruli shares similar epitopes.
5. Loss of Immunoregulation• Loss of Self tolerance - caused by over activity or lowered
activity of T and B- cells
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Meachanisms of autoimmunity
AUTOIMMUNITY
SEQUESTERED ANTIGENS
MOLECULAR MIMICRY
POLYCLONAL B CELL ACTIVATION
NEO ANTIGENS
CROSS REACTING ANTIGENS
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Chemical agents
Infections
Drugs
Physical agents
ANTIGENNEO ANTIGEN!!
IMMUNE RESPONSE
Neoantigens
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Cross reacting antigens• Cross reaction – foreign antigens• Organ specific antigens • Heterologous organ specific antigens
• Neurological rabies vaccine• Streptococcus M protein – myocardium• Glomerulonephritis
NATIVE ANTIGEN
FOREIGN ANTIGEN
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Molecular mimicry
• M. tb = Joint membranes• Coxsackie = myocardium
HUMAN ANTIGEN
NON SELF ANTIGEN
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Polyclonal B cell activation
BODYANTIGEN CORRESPONDING B CELL ACTIVATION
POLYCLONAL B CELL ACTIVATION
Ig M
CHEMICALS
ANTIBIOTICS
VIRUSES AND BACTERIA
ENZYMES
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Sequestered antigens
LENS
FOREIGN ANTIGEN
IMMUNE RESPONSE
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Classification of autoimmune diseases
HEMOCYTOLYTIC LOCALISEDSYSTEMIC (NON ORGAN
SPECIFIC)
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Classification of Autoimmune Diseases• Systemic- the auto-immunity is directed against an antigen that is
present at many different sites and can include involvement of several organs • Organ specific - Organ specific means the auto-immunity is directed
against a component of one particular type of organ.• Both – can get overlap
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Classification of Autoimmune Diseases
• Broadly classified into 3 groups1. Haemolytic autoimmune diseases2. Localised AID3. Systemic autoimmune diseases
1. Hemolytic 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, etc.
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Classification of Autoimmune Diseases2. 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)
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Classification of Autoimmune Diseases
3. Systemic autoimmune diseases orNon-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: cross-reaction between antibodies to streptococcus
and auto-antibodies.
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HEMOCYTOLYTIC LOCALIZED SYSTEMIC
Autoimmune hemolytic anemia
Grave`s disease SLE
Hashimoto`s thyroididtis RA
Myasthenia gravis Sjogren`s syndrome
Multiple sclerosis
Addison’s disease
Type 1 dm
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Examples of autoimmune disorders include:
• Rheumatoid arthritis (RA)
• Systemic lupus erythematosus (SLE)
• Hashimoto's disease
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Diagnosis:
The health care provider will do a physical exam. Signs depend on the type of disease.
Tests that may be done to diagnose an autoimmune disorder may include:
• Antinuclear antibody tests• Autoantibody tests• CBC• C-reactive protein (CRP)• Erythrocyte sedimentation rate (ESR)
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Hemocytolytic Autoimmune hemolytic anemia• Autantibodies to RBCs produced• No lysis
Phagocyte destroys RBC
LYSIS ONLY IF Complement attaches to antigen
antibody complex facilitating lysis of RBC
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Warm antibody
Drugs
IgG
incomplete
Cold antibody
Syphilis
IgM
4 Deg
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LocalizedHashimoto’s Thyroiditis
• Thyroglobulin – autoantigen.
• Antithyroglobulin antibodies
• Enlargement of thyroid gland
• Symptoms of hypothyroidism
• Female predisposition
• HISTOLOGY – Lymphocytes, Histiocytes, Plasma cells
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Grave`s disease
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Myasthenia Gravis
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Multiple sclerosis
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Addisons• helps maintain blood pressure and
cardiovascular function;
• helps slow the immune system's inflammatory response
• helps balance the effects of insulin
in breaking down sugar for energy
• and helps regulate the metabolism of proteins, carbohydrates, and fats.
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Type I DM
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Systemic SLE – disintegrating leucocytes. Nucleoproteins – auto antigens –
autoantibodies – activate complement
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Rheumatoid arthritis
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Sjogren’s syndrome
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Diagnosis• Clinical• Blood sugar profile• Thyroid profile
• Rheumatoid factor – Latex agglutination
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SLE, Sjogren`s etc..
• LE Bodies• Antinuclear antibodies ELISA IFA
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