chapter 16

Question 1

What is tolerance?

Answer 1

prevention of an immune response against self antigens

Question 2

-deletion of lymphocytes before they mature
-takes place in generative lymphoid organs

Answer 2

Central Tolerance

Question 3

-either renders self-reactive lymphocytes nonresponsive or actively generates inhibiting lymphocytes
-occurs outside bone marrow and thymus

Answer 3

peripheral tolerance

Question 4

high affinity for self antigen results in induction of __________in B and T cells

Answer 4

apoptosis

Question 5

Describe how B cells have been shown to undergo receptor editing:

Answer 5

-A second V gene segment is rearranged into the first rearrangement
– Often, this results in rendering the receptor inactive
– Occasionally, a new non–self-specific receptor can be generated

Question 6

peripheral tolerance regulates __________________in the circulation.

Answer 6

autoreactive cells

Question 7

Dependent mechanisms occur as Treg cells express high levels of inhibitory __________________molecules.

Answer 7

CTLA-4

Question 8

Independent mechanisms rely upon secretion of ___________________________into the surrounding area, shutting down nearby cells’ responses.

Answer 8

cytokines (IL-10, TGF-β, IL-35)

Question 9

A TREG that interacts with an APC can suppress T cells that engage separate Ag-MHC class II complexes on the APC surface–this phenomenon is known as ___________________

Answer 9

linked supression

Question 10

Autoimmunity is caused by?

Answer 10

failure of tolerance processes
-may be organ-specific or systemic
-may involve antibodies, T cells, immune complexes, or any combination of elements

Question 11

What is the mechanism for Hashimoto’s thyroiditis?

Answer 11

Autoantibodies and sensitized TH1 cells specific for thyroid Ag
are produced

Question 12

Describe the effects of Hashimoto’s thyroiditis:

Answer 12

More common in women
– Ab produced interferes with iodine uptake
» Decreases thyroid function leading to hypothyroidism
– Induces DTH response in the thyroid
» Inflammation results in a goiter―visible enlargement of the
thyroid gland

Question 13

What causes Type 1 diabetes mellitus?

Answer 13

Caused by autoimmune attack against insulin-producing beta cells
in the pancreas

Question 14

What is the mechanism for Type 1 diabetes mellitus?

Answer 14

– CTLs infiltrate the pancreas and activate macrophages
» This is followed by cytokine release and production of autoantibodies,
which may activate complement or ADCC activities by NK cells
» Eventual DTH response releases destructive enzymes

Question 15

What is the mechanism for Myasthenia gravis?

Answer 15

Autoantibodies that bind acetylcholine receptors on motor
end plates of muscles

Question 16

What are the effects of Myasthenia gravis?

Answer 16

– Block the normal binding of acetylcholine, induce complement-mediated lysis of cells
– Result is a progressive weakening of the skeletal muscles

Question 17

How do we treat Myasthenia gravis?

Answer 17

increasing acetylcholine levels, decreasing Ab production, and/or removing Ab

Question 18

What are the organ specific diseases?

Answer 18

Hashimoto’s thyroiditis
Type 1 diabetes mellitus
Myasthenia gravis

Question 19

What is the mechanism for Systemic lupus erythematosus?

Answer 19

Auto-Ab against DNA, histones, other self structures

Question 20

Symptoms of lupus result from specificity of Ab produced and can include:

Answer 20

– Fever, weakness, arthritis, skin rashes, and kidney dysfunction
– Type III hypersensitivity reactions often induce damage

Question 21

What are some factors of Rheumatoid arthritis?

Answer 21

» Auto-Ab reactive with determinants in the Fc region of
IgG
» Form immune complexes and activate complement
cascades

Question 22

What are several possible mechanisms have been proposed for the induction of autoimmunity?

Answer 22

– Infections and molecular mimicry
– Infections that induce genetic changes
– Damage/stress events that expose sequestered Ag
– Foods that alter gut microbial balance, promoting chronic inflammation and hypersensitivity reactions

Question 23

autograft

Answer 23

self tissue grafted to another self area (skin grafts, blood vessels)

Question 24

isograft

Answer 24

transplant between genetically identical individuals (inbred strains of mice, identical twins)

Question 25

allograft

Answer 25

tissue transferred between genetically different members of the same species (majority of transplant cases)

Question 26

xenograft

Answer 26

tissue transferred between different species (baboon heart into a human)

Question 27

describe specificity and memory in allograft rejection:

Answer 27

• First-set rejection is complete by 12–14 days, but memory of the anti-graft response is generated
• Second-set rejection occurs much faster, completing within only 5–6 days

Question 28

What cells mediate graft rejection?

Answer 28

CD4+ T cells seem to be more important than CD8+, but both together strongly facilitate rejection

Question 29

Siblings have a ____% chance of MHC identitiy.

Answer 29

25

Question 30

parent-to-child grafts have a ____% MHC match due to always having one MHC haplotype in common

Answer 30

50

Question 31

how do blood group antigen differences play a role in graft tolerance?

Answer 31

-most intense graft rejections
-they are the first items to be matched between donor/recipient

Question 32

describe the sensitization stage of graft rejection:

Answer 32

-CD4+ and CD8+ T cells recognize alloantigens expressed on foreign graft cells
-The T cells proliferate in response
-May recognize the donor MHC molecules directly (direct presentation)
-May recognize peptides from donor MHCs presented in the
recipient’s own APC MHC molecules (indirect presentation)
– Memory T cells generated

Question 33

describe the effector stage of graft rejection:

Answer 33

– Generally involves heavy infiltration of recipient cells into graft
tissue (similar to a DTH reaction)
– Can rarely involve production of antibodies against donor
HLA molecules or endothelial Ag

Question 34

describe specific immunosuppressive therapy:

Answer 34

Ideal immunosuppressant would be antigen-specific
– Monoclonal antibodies can achieve some of this desired effect
» mAb to CD3 depletes T cells prior to transplant
– Soluble CTLA-4 fusion proteins can induce T-cell anergy

Question 35

immunologically privileged sites:

Answer 35

-Allografts in such areas are less likely to experience rejection
- Corneal transplants are highly successful

Question 36

What is the current idea for inducing transplantation tolerance?

Answer 36

-generation of mixed hematopoietic chimerism prior to transplantation
-Theory is that the cells will “get used to each other” and generate
tolerance to the graft before it actually takes place