[W9] Immunological tolerance and Autoimmunity

Question 1

What is autoimmunity?

Answer 1

When the immune system attacks the body’s own tissues using similar mechanisms as for pathogen defense.

Question 2

What are the three main immune components involved in autoimmunity?

Answer 2

• Autoreactive T cells
• Autoantibodies
• Innate immune activation

Question 3

What is an autoantigen?

Answer 3

A self-protein that triggers an autoimmune response.

Question 4

What is self-tolerance?

Answer 4

The immune system’s ability to not respond to self-antigens.

Question 5

What causes autoimmunity?

Answer 5

A failure of self-tolerance.

Question 6

Why do some T cells recognize self-antigen?

Answer 6

TCRs are randomly generated, so some T cells naturally bind self-antigens.

Question 7

What is central tolerance?

Answer 7

Deletion of self-reactive T or B cells during development in the thymus or bone marrow.

Question 8

What is peripheral tolerance?

Answer 8

Mechanisms that regulate self-reactive lymphocytes that escape central deletion.

Question 9

What is the importance of co-stimulation in T cell activation?

Answer 9

T cells require Signal 2 to activate; without it, they become anergic.

Question 10

What is positive selection?

Answer 10

T cells must weakly bind self-MHC to survive.

Question 11

What is negative selection?

Answer 11

T cells that bind self-peptides too strongly are deleted.

Question 12

Which cells mediate negative selection?

Answer 12

Bone marrow–derived dendritic cells in the thymic medulla.

Question 13

What happens to B cells that bind multivalent self-antigen?

Answer 13

They undergo deletion or receptor editing.

Question 14

What happens to B cells that bind soluble self-antigen?

Answer 14

They become anergic.

Question 15

What happens to B cells that don’t cross-link with antigen?

Answer 15

They become ignorant and may mature.

Question 16

What is organ-specific autoimmunity?

Answer 16

Autoimmunity directed at a specific organ (e.g., Type 1 Diabetes, MS).

Question 17

What is systemic autoimmunity?

Answer 17

Autoimmunity that affects multiple organs (e.g., Rheumatoid Arthritis).

Question 18

What are the types of autoimmune mechanisms?

Answer 18

• Type II: Antibody to surface antigens
• Type III: Immune complex deposition
• Type IV: T cell–mediated

Question 19

What immune mechanism causes Type 1 Diabetes (T1D)?

Answer 19

CD8⁺ T cells kill pancreatic β cells (Type IV autoimmunity).

Question 20

What are symptoms of Type 1 Diabetes (T1D)?

Answer 20

• High blood glucose
• Glucose in urine
• Weight loss
• Ketoacidosis

Question 21

How is Type 1 Diabetes (T1D) treated?

Answer 21

Insulin replacement therapy.

Question 22

What is targeted in Multiple Sclerosis (MS)?

Answer 22

Myelin sheath in the brain and CNS.

Question 23

What type of autoimmunity is Multiple Sclerosis (MS)?

Answer 23

Type IV – T cell–mediated.

Question 24

What drug reduces lymphocyte entry into the brain in Multiple Sclerosis (MS)?

Answer 24

Natalizumab (anti-α4 integrin antibody).

Question 25

What immune components are involved in Rheumatoid Arthritis (RA)?

Answer 25

* Immune complexes (Type III) * CD4⁺ T cells and macrophages (Type IV)

Question 26

What is rheumatoid factor?

Answer 26

An autoantibody (IgG) that forms immune complexes.

Question 27

What tissue is primarily affected in Rheumatoid Arthritis (RA)?

Answer 27

The synovium (lining of joints).

Question 28

What causes bone destruction in Rheumatoid Arthritis (RA)?

Answer 28

Osteoclast activation and release of MMPs (matrix metalloproteinases).

Question 29

Can autoimmune diseases be cured?

Answer 29

No – they can only be managed.

Question 30

What are the three main treatment strategies for autoimmunity?

Answer 30

* Anti-inflammatories (e.g., NSAIDs, corticosteroids) * Immunomodulators (e.g., Natalizumab, Infliximab) * Functional replacement (e.g., insulin for T1D)

Question 31

What is the risk of bone marrow transplantation as a cure?

Answer 31

High-risk and not commonly used.

Question 32

What enforces tolerance in the immune system?

Answer 32

Central and peripheral tolerance, and co-stimulation requirements.

Question 33

What causes systemic vs organ-specific autoimmunity?

Answer 33

Systemic involves widespread inflammation; organ-specific targets one tissue.

Question 34

What is the primary goal of autoimmune treatment?

Answer 34

Reduce inflammation, suppress autoimmunity, and preserve function.