Exam 3: Dr. Pinchuk Autoimmune Diseases

Question 1

In healthy individuals, what is the immune system tolerant?

Answer 1

Self antigens

Question 2

What are autoimmune diseases cause by?

Answer 2

The loss of tolerance

Question 3

What are the central tolerance mechanisms that contribute to immunological self-tolerance?

Answer 3

Negative selection in the bone marrow and thymus

Expression of tissue specific proteins in the thymus

Question 4

What are the peripheral tolerance mechanisms that contribute to immunological self-tolerance?

Answer 4

No lymphocyte access to some tissues
Suppression of autoimmune responses by regulatory T cells
Induction of anergy in auto reactive B and T cells

Question 5

What do the effector mechanisms of autoimmunity resemble?

Answer 5

Those causing hypersensitivity reactions

Question 6

What are the auto antigens for lupus?

Answer 6

DNA
Histones
Ribosomes
snRNP
scRNP

Question 7

What are the consequences for lupus?

Answer 7

Glomerulonephritis
Vasculitis
Arthritis

Question 8

What are the 3 mechanisms that destroy erythrocytes in autoimmune hemolytic anemia?

Answer 8

FcR+ cells in spleen
Complement activation and CR1+ cells in spleen
Complement activation and intravascular hemolysis

Question 9

What do FcR+ cells in spleen cause?

Answer 9

Phagocytosis and erthyrocyte destruction

Question 10

What does complement activation and CR1+ cells in spleen cause?

Answer 10

Phagocytosis and erthyrocyte destruction

Question 11

What does complement activation and intravascular hemolysis cause?

Answer 11

Lysis and erythrocyte destruction

Question 12

What can autoantibodies against cell-surface receptors do?

Answer 12

Either stimulate or inhibit the receptor’s function

Question 13

What causes myasthenia gravis?

Answer 13

Signaling from nerve to muscle across the neuromuscular junction is impaired

Question 14

What is major example of rheumatic diseases caused by autoimmunity?

Answer 14

Systemic lupus erythematosus

Question 15

What are the pathogenic mechanisms for lupus?

Answer 15

Type III hypersensitivity
A large amount of small immune complexes are formed due to the availability of autoantigen and autoantibody. Immune complexes deposit in the capillaries if various tissues. Immune complexes can either enter through the fenestrations of glomerular capillaries and become trapped in the basement membrane

Question 16

What is the mechanism of autoantigen accumulation for lupus?

Answer 16

Possible defect in the clearance of apoptotic cells:

Macrophages from lupus patients have a reduced capacity to engulf apoptotic cells in vitro

Question 17

Describe type I diabetes

Answer 17

T cell responses and antibodies are made against insulin and other specialized proteins of the pancreatic β cell islets of Langerhan’s

Question 18

What can the two recently developed therapies that target different aspects of the rheumatoid arthritis do?

Answer 18

Eliminate B cells in a patient, which is okay because in theses patients most B cells are auto-reactive

Question 19

What happens with ADCC in rheumatoid arthritis?

Answer 19

Lysis of B cells by NK cells and the therapeutic anti-CD20 antibody rituximab

Question 20

What are the causes of rheumatoid arthritis?

Answer 20

Effector CD4 T cells and antibody

Question 21

What is a feature of all autoimmune diseases?

Answer 21

Breaking T cell tolerance

Question 22

Describe what happens in breaking T cell tolerance

Answer 22

Incomplete deletion of self-reactive T cells in the thymus, APECED
Insufficient control of T cell co-stimulation (CTLA-4 deficiency)
Lack of Treg cells, deficiency in FoxP3 is called immune dysregulation, polyendocrynopathy, enterophathy, and C-linked syndrome (IPEX)

Question 23

What is HLA?

Answer 23

The dominant genetic factor affecting susceptibility to autoimmune disease

Question 24

What is the HLA allotrope for ankylosing spondylitis?

Answer 24

B27 (MHC class I)

Question 25

What is autoimmunity initiated by?

Answer 25

Disease-associate HLA allotypes presenting antigens to autoimmune T cells

Question 26

What do animal models of autoimmune disease demonstrate?

Answer 26

That autoreactive T cell clones can transfer disease

Question 27

What is an example of an infection as environmental facotrs that can trigger autoimmune disease?

Answer 27

Streptococcal cell wall stimulates antibody response

Some antibodies cross-react with hear tissue, causing rheumatic fever

Question 28

How can autoimmune T cells be activated?

Answer 28

In a pathogen-specifc of non-specific manner by infection

Question 29

What can predispose to autoimmune disease?

Answer 29

Genetic and environmental factors