Tolerance and Autoimmunity

Question 1

What is an antigen?

Answer 1

Any substance capable of generating an immune response

not just an inflammatory response

Question 2

What is immunological tolerance?

Answer 2

Unresponsiveness of the immune system to an antigen

E.g. fetus, gut flora, plant pollens

Question 3

What is autoimmunity?

Answer 3

An immune response to self-antigens

Due to failure of immunological tolerance

Question 4

What process is mainly responsible for immunological tolerance?

When does this happen?

Answer 4

Central tolerance

In fetus and declines after birth

Question 5

What is clonal deletion?

Answer 5

Part of central tolerance

Immature lymphocytes (in fetus) that recognise self-antigens are deleted by apoptosis

Question 6

What is clonal anergy?

Answer 6

Part of central tolerance

Immature lymphocytes that recognise self-antigens are regulated by regulatory T lymphocytes

Question 7

Where does central tolerance develop?

Answer 7

Thymus and bone marrow

Most active in fetus

Question 8

What is peripheral tolerance?

Answer 8

Prevents immune responses to fetus, gut flora, plant pollens etc.

Active throughout life

Develops in peripheral lymphoid tissues

Question 9

What is clonal suppression

Answer 9

Part of the peripheral tolerance immunity system (throughout life)

Mature lymphocytes that recognise self antigens are suppressed by regulatory T lymphocytes

Question 10

How can autoimmunity be measured?

Answer 10

By measuring the activity of B cells and their antibodies they produce

Almost all loss of tolerance seems to be B cell mediated

Question 11

Which HLA gene is linked to ankylosing spondylitis?

Answer 11

HLA-B27

Question 12

Which HLA gene is linked to systemic lupus erythematosus?

Answer 12

HLA-DR2

Question 13

Which HLA gene is linked to autoimmune hepatitis, Sjogren’s syndrome, T1DM, SLE?

Answer 13

HLA-DR3

Question 14

Which HLA gene is linked to RA, T1DM?

Answer 14

HLA-DR4

Question 15

What do class I MHC/HLA genes present?

What cells are they found on?

Answer 15

Present self antigens, cancer, viruses

Are on every cell

Question 16

What do class II MHC/HLA genes present?

What cells are they found on?

Answer 16

Present antigens from phagocytosis

On phagocytes and antigen presenting cells

Question 17

How can autoimmunity and MHC antigen presentation cells be linked?

Answer 17

It is thought that variance in Class I MHC proteins can predispose people to autoimmune conditions

Question 18

Describe the principle of molecular mimicry

Answer 18

The immune system is exposed to a foreign antigen and reacts, however the antigens can sometimes look like self antigens

This can lead to a cross reaction in another part of the body leading to an autoimmune response

Streptococcal infection - the antigens look similar to self-antigens on the heart valve, and so the heart valve is attacked which leads to rheumatic fever

Question 19

Which auto-antibody can be identified in Grave’s disease?

Answer 19

TSH receptor

Question 20

Which auto-antibody can be identified in rheumatoid arthritis?

Answer 20

RhF

Question 21

Which auto-antibody can be identified in coeliac disease?

Answer 21

Anti-gliadin and anti-endomysial

Question 22

Which auto-antibody can be identified in Hashimoto’s thyroiditis?

Answer 22

Thyroid peroxidase enzyme

Question 23

Which auto-antibodies can be identified in SLE?

Which is more sensitive?

Answer 23

ANA - 95% sensitivity

dsDNA - 50% sens, 99% specific

Question 24

Why are steroids useful in treating acute presentations of autoimmune disease?

Answer 24

They have anti-inflammatory and immunosuppressive properties

They reduce cytokines (IL-2) and cell-mediated and humoral immunity

Question 25

Give an example of a monoclonal antibody drug.

What can it be used to treat?

Answer 25

Infliximab - anti-TNF cytokine

Used in RA, Crohn’s, ankolysing spondolysis

Question 26

What is the prevalence of autoimmune disease in developed countries?

Which diseases have the top prevalence?

Answer 26

1-3%

Grave’s
RA