Autoimmunity

Question 1

What are autoimmune diseases caused by?

Answer 1

Inappropriate B cell (antibody) and/or T cell immune response against self-antigens

Question 2

Antigen expressed on your own cell

Answer 2

Self antigen or auto-antigen

Question 3

Cell that binds a self antigen

Answer 3

Autoreactive cell

Question 4

Antibody that binds a self antigen

Answer 4

autoantibody

Question 5

What are the two classifications of autoimmune diseases?

Answer 5

Organ-specific and systemic

Question 6

Immune response targets self-antigens in a specific organ

Answer 6

organ-specific autoimmune disease

Question 7

Immune response targets self antigens in multiple organs

Answer 7

Systemic autoimmune diseases

Question 8

Many autoreactive cells are eliminated during development in the _____ (_ cells) and ____ ____ (_ cells)

Answer 8

Thymus (t cells)
Bone marrow (B cells)

Question 9

How are autoreactive cells eliminated in the thymus or bone marrow?

Answer 9

Developing B and T cells are presented with self-antigens - if the developing B or T cell binds strongly to a self antigen - it is killed by apoptosis

Question 10

Are all self-recognizing B and T cells destroyed by central tolerance?

Answer 10

No, not 100% effective since not all self-antigens are presented in the bone marrow or thymus

Question 11

Many autoreactive T cells and B cells are also eliminated or inactivated where else (i.e. other than thymus or bone marrow)?

Answer 11

Peripheral tissues

Question 12

What is anergy?

Answer 12

Circulating autoreactive B or T cells are inactivated in the periphery

Question 13

Autoimmune diseases occur when autoreactive T cells and or autoantibodies bind their specific self antigen in a process called what?

Answer 13

Autoimmune response

Question 14

What are factors that increase our susceptibility to autoimmune diseases?

Answer 14

Genetic factors and environmental factors

Question 15

How do genetic factors most likely increase susceptibility to autoimmune disorders?

Answer 15

By impaired removal of autoreactive T/B cells
Having certain HLA genes makes it more likely to develop autoimmune disorders
sex (male vs. female)

Question 16

_____ is strongly associated with certain autoimmune diseases.

Answer 16

HLA

Question 17

What encodes for MHC molecules?

Answer 17

HLA - human leukocyte antigen

Question 18

Why do certain HLAs have higher incidences of autoimmunity?

Answer 18

HLAs have different shapes which render them more susceptible to bind to self-antigens (based on structural binding/shape of cleft)

Question 19

Which sex is most affected by autoimmunity?

Answer 19

females (i.e. female hormones obviously play a role in susceptibility to certain autoimmune diseases)

Question 20

A normal immune response against a pathogen can “spread” to an autoimmune response through?

Answer 20

Molecular mimicry

Question 21

What is molecular mimicry?

Answer 21

When a foreign antigen and a self-antigen are structurally similar.
Development of normal immunity against pathogenic antigen leads to immunity against structurally similar self-antigen

Question 22

How can cardiopathy manifest with rheumatic fever?

Answer 22

Heart muscle expresses an antigen similar to a streptococcal antigen.

Question 23

Describe diabetes type I.

Answer 23

Autoreactive CTLs attack beta cells of pancreas - no longer secrete insulin leading to hyperglycemia

Question 24

What evidence is there for molecular mimicry in IDDM?

Answer 24

Coxsackie virus antigen resembles a beta-cell antigen (GAD65),
However, need some initial damage to pancreas to cause presentation of GAD65 to cause CTLs to kill beta cells.

Question 25

Describe MS.

Answer 25

Myelin sheath of nerve fibers in the brain and SC are destroyed by autoreactive Th1 cells (and autoantibodies).

Question 26

What molecular mimicry might be at play for MS?

Answer 26

Epstein-Barr virus antigen is structurally similar to a myelin sheath antigen.

Question 27

How can tissue damage lead to autoimmunity?

Answer 27

Many antigens are hidden in organs or tissues and, only through tissue damage, are they exposed allowing autoimmunity to occur

Question 28

Describe sympathetic opthalmia.

Answer 28

Get trauma to one eye leading to inflammation and release of antigens which B and T cells are usually NEVER exposed to.
Autoreactive B and T cells bind to epitope and undergo clonal expansion.
If inflammation occurs again, they can enter the tissues and lead to blindness in the eyes.

Question 29

What is the environmental trigger for systemic lupus erythematosus?

Answer 29

UV light (only in certain subsets)

Question 30

Almost all SLE (lupus) patients have autoantibodies against what?

Answer 30

dsDNA - antinuclear autoantibodies

Question 31

How is lupus systemic?

What does it ultimately lead to?

Answer 31

every cell in the body has dsDNA, multiple organs can be affected
ultimately leads to organ failure

Question 32

What is the main hallmark of lupus?

Answer 32

Autoantibody deposition

Question 33

Describe SLE as it pertains to endothelial cells.

Answer 33

Autoantibodies get deposited on the endothelial cells and form immune complexes.
Self-antigens in the circulation bind to these.
Neutrophils in the blood bind to the antibodies and try to internalize, get frustrated and release toxic enzymes which damage endothelial cells.

Question 34

Describe the vicious cycle of lupus.

Answer 34

Damaged tissue cells release more autoantigens, so more autoantibodies bind, which causes more damage…