Chapter 6 Guerin Lecture Part 2

Question 1

Pathologic autoimmunity “confirmed” when… (3)

Answer 1

Presence of immune reaction specific for self
Evidence that reaction is not secondary to tissue damage
Absence of another well-defined disease

Question 2

What are immune-mediated inflammatory diseases?

Answer 2

Disorders in which chronic inflammation is the prominent component

Question 3

Systemic autoimmune diseaeses (4)

Answer 3

SLE
Rheumatoid arthritis
Systemic sclerosis
Sjogren syndrome

Question 4

Organ-Specific autoimmune diseases (7)

Answer 4

Autoimmune hemolytic anemia
Myasthenia gravis
Graves disease
Type 1 diabetes Mellitus
Goodpasture syndrome
Inflammatory Bowel Disease
Multiple sclerosis

Question 5

Why is type 1 diabetes mellitus an organ-specific autoimmune disease?

Answer 5

because it attacks the beta cells of the pancreatic islets

Question 6

Why is muscle sclerosis an organ-specific autoimmune disease?

Answer 6

because it attacks the CNS myelin

Question 7

Why is SLE a systemic autoimmune disease?

Answer 7

have diversity of antibodies directed against DNA, platelets, RBCs, and protein-phospholipid complexes

Question 8

What is immunologic tolerance?

Answer 8

process where immune system has learned to tolerate our own self antigen

Question 9

How does our body recognize self antigens?

Answer 9

through receptors made via somatic recombination of genes

Question 10

How does our body make sure receptors that recognize self antigens are not present?

Answer 10

the cells with self recognizing receptors must be eliminated or inactivated as soon as they recognize self antigen

Question 11

2 types of immunologic tolerance

Answer 11

central and peripheral

Question 12

What occurs during central tolerance with T cells?

Answer 12

1. APC presents self antigen to T cell
2. T cells with high affinity TCR’s for self antigens are made
3. Negative selection or deletion occurs
4. Some CD4+ that see self antigens in the thymus do not die but turn into regulatory T cells

Question 13

What is negative selection?

Answer 13

1. Occurs in the thymus for central tolerance

2. Immature lymphocytes that encounter self antigens in the thymus and die via apoptosis

Question 14

What occurs during central tolerance with B cells?

Answer 14

1. Occurs in bone marrow
2. B cells that strongly recognize self antigens may undergo receptor editing
3. If receptor editing does not occur, self reactive cells undergo apoptosis

Question 15

What is receptor editing?

Answer 15

Occurs with B cells in bone marrow

Rearrangement of genes on receptor to express new antigen receptor

Question 16

What occurs during peripheral tolerance for T cells?

Answer 16

APC presents self antigen to T cell in periphery and there is no/weak costimulation
T cells undergo anergy (made inactive/unresponsive)
Or die via apoptosis

Question 17

What occurs during peripheral tolerance for B cells?

Answer 17

B cells encounter self antigen in peripheral tissues and without a T helper cell, the B cells undergo anergy (made inactive/unresponsive)

Question 18

Function of Regulatory T cells in peripheral tolerance

Answer 18

suppress and prevent immune reactions against self antigens

ex. play a role in mother’s acceptance of the fetus that has paternal antigens

Question 19

Defects in regulatory T cells and accepting the fetus

Answer 19

can lead to recurrent spontaneous abortions

Question 20

Immune-Privileged Sites

Answer 20

Testis, eye, brain

Where antigens do not communicate with blood and lymph

Question 21

What if antigen occurs in immune-privileged site

Answer 21

antigens are released after trauma or infection

prolong tissue inflammation and injury

Question 22

What general factors contribute to autoimmunity?

Answer 22

genetic susceptibility and environmental triggers

Question 23

What changes can initiate autoimmunity? (3)

Answer 23

Defective tolerance or regulation
Abnormal display of self antigens
Inflammation or initial innate immune response

Question 24

How can infections lead to autoimmunity? (2)

Answer 24

Induction of costimulators on APCs

Molecular mimicry

Question 25

Classic example of molecular mimicry

Answer 25

Rheumatic heart disease

Antibodies against streptococcal proteins cross-react with myocardial proteins and cause myocarditis

Question 26

How and what viruses can cause production of autoantibodies?

Answer 26

EBV and HIV cause polyclonal B-cell activation producing autoantibodies

Question 27

What influence does the microbiome have on autoimmunity

Answer 27

Normal gut and skin microbe may provide us with non pathogenic microbes that dont hurt us
Help maintain proportions of effector and regulatory T cells

Question 28

General Features of autoimmune diseases (4)

Answer 28

chronic, progressive, epitope spreading, excessive or abnormal Th1 and Th17 responses

Question 29

What is epitope spreading?

Answer 29

An initial immune response occurs and causes tissue damage which releases other antigen and activated lymphocytes

Question 30

What do systemic autoimmune diseases involve?

Answer 30

blood vessels and connective tissue

called “collagen vascular” or “connective tissue” diseases