autoimmunity - microbiology - immunology - dr.someshwaran rajamani december 2015

AUTOIMMUNITY

Dr. R. Someshwaran, MBBS, MD., Assistant professor, Department of Microbiology,

Karpagam Faculty of Medical Sciences and Research, Othakalmandapam, Coimbatore-641032

05/03/2023 2

Objectives• Define Autoimmune disease• Classify them• Aid in Diagnosis

05/03/2023 3

Introduction

05/03/2023 4

Introduction

05/03/2023 5

Introduction

05/03/2023 6

05/03/2023 7

05/03/2023 8

05/03/2023 9

Molecular mimicry

05/03/2023 10

Balanced immune system

05/03/2023 11

05/03/2023 12

05/03/2023 13

ETIOLOGY OF AID

05/03/2023 14

05/03/2023 15

05/03/2023 16

05/03/2023 17

05/03/2023 18

05/03/2023 19

05/03/2023 20

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.

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

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

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

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.

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

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

Autoimmunity

Contributing Factors• Defects in the immune system.• Influence of hormones• Environmental conditions

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

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.

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

Meachanisms of autoimmunity

AUTOIMMUNITY

SEQUESTERED ANTIGENS

MOLECULAR MIMICRY

POLYCLONAL B CELL ACTIVATION

NEO ANTIGENS

CROSS REACTING ANTIGENS

Chemical agents

Infections

Drugs

Physical agents

ANTIGENNEO ANTIGEN!!

IMMUNE RESPONSE

Neoantigens

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

Molecular mimicry

• M. tb = Joint membranes• Coxsackie = myocardium

HUMAN ANTIGEN

NON SELF ANTIGEN

Polyclonal B cell activation

BODYANTIGEN CORRESPONDING B CELL ACTIVATION

POLYCLONAL B CELL ACTIVATION

Ig M

CHEMICALS

ANTIBIOTICS

VIRUSES AND BACTERIA

ENZYMES

Sequestered antigens

LENS

FOREIGN ANTIGEN

IMMUNE RESPONSE

Classification of autoimmune diseases

HEMOCYTOLYTIC LOCALISEDSYSTEMIC (NON ORGAN

SPECIFIC)

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

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.

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)

05/03/2023 44

05/03/2023 45

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.

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

Examples of autoimmune disorders include:

• Rheumatoid arthritis (RA)

• Systemic lupus erythematosus (SLE)

• Hashimoto's disease

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)

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

Warm antibody

Drugs

IgG

incomplete

Cold antibody

Syphilis

IgM

4 Deg

LocalizedHashimoto’s Thyroiditis

• Thyroglobulin – autoantigen.

• Antithyroglobulin antibodies

• Enlargement of thyroid gland

• Symptoms of hypothyroidism

• Female predisposition

• HISTOLOGY – Lymphocytes, Histiocytes, Plasma cells

Grave`s disease

Myasthenia Gravis

Multiple sclerosis

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.

Type I DM

Systemic SLE – disintegrating leucocytes. Nucleoproteins – auto antigens –

autoantibodies – activate complement

Rheumatoid arthritis

Sjogren’s syndrome

Diagnosis• Clinical• Blood sugar profile• Thyroid profile

• Rheumatoid factor – Latex agglutination

SLE, Sjogren`s etc..

• LE Bodies• Antinuclear antibodies ELISA IFA

05/03/2023 64