Autoimmunity

Question 1

What is autoimmunity ? And difference with autoimmune disease ?

Answer 1

Immune response against the host due to loss of immunological tolerance of self antigens

Autoimmune disease is the diseased caused by tissue damages or physio changes due to autoimmunity

Question 2

What are the the two main patterns of auto immune disease ?

Answer 2

Organ specific : one or more self antigens from SINGLE organ

Non-organ specific : wide distributed self antigens throughout body

Question 3

What are the immune mechanisms causing tissue damage ? What does it depend on?

Answer 3

Depends on type of hypersensitivity reaction

Due to Autoantibodies : Complement activation , ADCC, Neutrophil activation
Due to Autoreactive T cells : cytotoxic T cells + macrophages

Question 4

What are the criteria for diagnosis of autoimmune disease ?

Answer 4

• Presence of autoAB/autoreactive T cells
• Levels of AB = disease severity
• AB or Tcells found at the site of damage
• Transfer of AB or Tcells to healthy host cause disease (IgG transfer from other )
• benefit from immunomodulatory therapy
• family history

Question 5

What does primary and secondary autoantibodies mean ?

Answer 5

Primary : AB are driving the disease

Secondary : AB production start during already declared disease , associated with intensity of disease

Question 6

When testing a patient to detect autoantibodies , what does sensitivity and specificity mean ?

Answer 6

Sensitivity : how many patient with disease are positive

Specificity : how any patient without disease an be excluded

Question 7

What can cause autoimmunity to become active and cause autoimmune disease ?

Answer 7

Central tolerance : failure to delete Autoreactive T cells
Peripheral mechanism: Regulatory T cell defect , impaired immunomodulation (cytokines), altered self antigens
Activation of autoreactive B cells : Tcell independant B cell activation(microbes) , Carrier effect (foreign-self antigens complex)

Question 8

What can trigger autoimmunity ?

Answer 8

Genetic factors : eg MHC variant

Environmental factors : Hormones , Infections, Drugs

Question 9

What is the mechanism of infection-induced autoimmune diseases ?

Answer 9

Immune response against microbes, some epitope of antigen look like self antigen (protein host ) > immune system can’t differentiate

Molecular mimicry

Question 10

Give eg of infection induced disease

Answer 10

Rheumatic fever : Strepto pyogenes (cardiac muscle)
Diabetes type I
Guillain-Barré syndrome

Question 11

Which treatment can be used in auto immune diseases ?

Answer 11

Plasmapheresis (t clear AB)
immunosuppressive drugs (decrease reactive T cells )
Anti-inflammatory drugs for tissue damage 
Replacement therapy or surgery for organ dysfunction 

Monoclonal AB

Question 12

What is monoclonal AB ?

Answer 12

Monovalent AB which bind to same epitope and are produced from a single B lymphocyte clone

Question 13

How are monoclonal AB made ?

Answer 13

Immunisation of mice to Specific epitope of antigen
Taking B lymphocytes and fusion with immortal myeloma cell (plasma cell cancer )
Culture

Question 14

What are the possible mechanism of action of the monoclonal AB ?

Answer 14

-Bind cell surface receptors : activate or inhibit intra cellular signalling
-Induce apoptosis
-bind cell surface and induce : ADCC(NK) , complement dependent cytotoxicity
-Internalisation : deliver toxins (antibody conjugate)
Blocking inhibitory effects on T cells (activating T cell )