Self-Tolerance & Autoimmunity (32)

Question 1

T/F: Tolerance occurs in both B and T cells

Answer 1

TRUE

Question 2

What is central self-tolerance? Where?

Answer 2

immature self-reactive lymphocytes die or alter specificity

occurs in thymus and bone marrow

Question 3

What is peripheral self-tolerance? Where?

Answer 3

mature self-reactive lymphocytes die, are turned off, or are suppressed by T-reg cells

maintained in lymph nodes and circulation

Question 4

What leads to the development of autoimmune disease?

Answer 4

breakdown of central or peripheral self-tolerance

Question 5

___ cells need exposure to self-antigens within bone marrow

Answer 5

B

Question 6

Tolerance occurs via 2 mechanisms:

Answer 6

clonal anergy

clonal deletion

Question 7

What is clonal anergy?

Answer 7

soluble self-antigen leads to anergy of cell without cross-linking of lymphoid receptor

Question 8

What is clonal deletion?

Answer 8

cross-linking of lymphoid receptor (slg) with self-antigen (MHC, etc) leads to apoptosis (clonal deletion)

Question 9

What are mechanisms of central tolerance in T cells?

Answer 9

clonal deletion - negative selection

those that react weakly are selected - positive selection

receptor editing: changes in TCR in self-reactive T cells

Question 10

What are mechanisms of peripheral tolerance?

Answer 10

immuno-priviledged organs
clonal anergy
clonal deletion
suppression

Question 11

The absence of T-cell costimulation is defined as ____

Answer 11

anergy

Question 12

Clonal deletion of T and B cells is through the _____

Answer 12

Fas/FasL interaction

Question 13

What happens when someone has autoimmune lymphoproliferative syndrome? (ALPS)

Answer 13

mutation in Fas and/or Fas ligand in humans

Question 14

What is clonal deletion in B cells?

Answer 14

activated T cell expresses Fas ligand

binds to Fas on B cell

induces apoptosis

seen with excessive suppressor activity or in absence of co-stimulation

Question 15

What is the phenotype of Treg cells in immune suppression?

Answer 15

CD4+CD25+Foxp3+

Question 16

What is the significance of Tregs and autoimmunity?

Answer 16

inhibit development of autoimmune disease in experimental models

Question 17

T/F: Treg cells proliferate when they recognize self-antigen

Answer 17

FALSE - they are able to recognize much smaller quantities of self-antigen which enables them to shut down other T cell and B cell responses to self-antigen

Question 18

What are the functions of Treg cells?

Answer 18

put the brakes on the inflammatory responses to pathogens

protect the body from “collateral damage” by the immune system

Question 19

T/F: Tregs are non-specific inhibitors

Answer 19

TRUE

Question 20

What are the main mechanisms of autoimmunity?

Answer 20

non-pathogenic autoimmunity

pathogenic autoimmunity

Question 21

What is non-pathogenic autoimmunity?

Answer 21

auto-antibodies are found in normal, healthy patients

antibodies against proteins in aged RBCs for removal

may detect auto-antibodies following infections

Question 22

What is pathogenic autoimmunity?

Answer 22

associated with either normal or abnormal immune response

results in clinical disease

Question 23

What is the normal immune response (pathogenic)?

Answer 23

exposure of previously hidden antigens

normally sequestered antigens (privileged sites, glandular tissue, brain, eyes, testes)

exposure of hidden epitopes secondary to tissue damage - inside cells after (1) heart attack or (2) chronic hepatitis

newly synthesized antigens (HLA II in thyroid tissues) with exposure to immune system

Question 24

What are mechanisms of pathogenic - abnormal autoimmunity?

Answer 24

1. cytokine dysregulation
2. loss of suppressor activity
   - Treg dysregulation common with cancer
   - variety of auto-immune diseases seen in cancer patients
3. genetic defects (Fas or Fas L defects)
4. molecular mimicry - microbial cross resistance

Question 25

What is molecular mimicry?

Answer 25

shared epitopes between infectious agents or parasites and self-antigen

can stimulus B or T cells

strep cell wall antigens share epitopes with cardiac, joint, kidney tissue

Question 26

What are predisposing factors to autoimmunity?

Answer 26

genetic predisposition

breed predisposition - LOW grade

intestinal microflora

Question 27

What are the types of autoimmune diseases?

Answer 27

organ specific - myasthenia gravis

systemic

Question 28

What is organ specific autoimmune disease?

Answer 28

self-antigen expressed on single organ or tissue

clinical signs are referable to organ dysfunction

Question 29

What are systemic autoimmune diseases?

Answer 29

autoantibody present for multiple self-antigens affecting a wide variety of organs

damage due to immune complex deposition - epithelial damage first

clinical signs vary

Question 30

What are immune (hypersensitivity) reactions?

Answer 30

all 4 mechanisms

Question 31

What are type II immune reactions?

Answer 31

auto-antibodies bind self proteins

ADCC

complement-mediated

Question 32

What are type III immune reactions?

Answer 32

auto-antibodies form immune complexes with self-antigens

create inflammation and resultant tissue injury

Question 33

What is systemic lupus erythermatosus?

Answer 33

Type II reaction
Type III reaction

Question 34

What are Type IV immune reactions?

Answer 34

not antibody mediated (i.e. Th1 response)

cytotoxic T-cells cause damage

insulin-dependent diabetes mellitus