16 Tolerance, Autoimmunity, and Transplantation

Question 1

What is tolerance?

Answer 1

The prevention of an immune response against self-antigens

Question 2

What’s the difference between central and peripheral tolerance?

Answer 2

Central - deletion of lymphocytes before they mature in generative lymphoid organs

Peripheral - renders self-reactive lymphocytes non-responsive or generates inhibiting lymphocytes, both outside bone marrow/thymus

Question 3

True or false: Central tolerance limits development of autoreactive T AND B cells

Answer 3

TRUE

Question 4

High affinity for self Ag results in…

Answer 4

…induction of apoptosis in B and T cells, with B cells undergoing receptor editing

Question 5

What cells are used in peripheral tolerance?

Answer 5

Regulatory CD4+T (Treg) cells

Question 6

How does Treg work in peripheral tolerance?

Answer 6

Contact dependent and independent mechanisms

Dependent: Treg cells express high levels of inhibitory CTLA-4 molecules

Independent: rely on secretion of cytokines into surrounding area to shut down nearby cells’ responses

Question 7

What is linked suppression?

Answer 7

Treg interaction with an APC that suppresses T cells that engage separate Ag-MHC class II complexes on the APC surface

Question 8

What is autoimmunity caused by?

Answer 8

The failure of tolerance processes which may be organ-specific or be systemic, and may involve antibodies/t-cells/immune complexes or any combination of elements

Question 9

What’s are examples of an autoimmune disease that targets specific organs?

Answer 9

Hashimoto’s thyroiditis: autoantibodies and sensitized Th1 cells specific for thyroid Ag are produced

Type I diabetes mellitus: caused by autoimmune attack against insulin-producing beta cells in the pancreas

Myasthenia gravis: autoantibodies that bind acetylcholine receptors on motor end plates of muscles which results in progressive weakening of the skeletal muscles

Question 10

What are examples of autoimmune diseases that are systemic?

Answer 10

Systemic lupus erythematosus (SLE): auto-AB against DNA, histones, and other self-structures

Rheumatoid arthritis: rheumatoid factors are produced such as auto-Ab reactive with determinants in the Fc region of IgG and form immune complexes and activate complement cascades

Question 11

True or False: both intrinsic and extrinsic factors can favor susceptibility to autoimmune disease

Answer 11

TRUE. Environmental factors favor the development of autoimmune disease

Question 12

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

Answer 12

Infection/molecular mimicry
Infections that induce genetic changes
Damage/stress events
Food that alter gut microbial balance

Or a combination of any of the above

Question 13

Why are women more susceptible than men to autoimmunity?

Answer 13

Females mount vigorous immune responses

Estrogen plays important role in immune response

Pregnancy for mother to tolerate the fetus with fetal cells being capable to persist for decades

Question 14

How can autoimmune diseases be treated?

Answer 14

General or pathway-specific immunosuppression through broad-spectrum therapies

strategies that target specific cell types

therapies that block steps in the inflammatory process

strategies that interfere with costimulation

Question 15

What are the degrees of immune response when it comes to graft transplantation immunology?

Answer 15

Autograft - self tissue grafted to another self area

Isograft - transplant between genetically identical individuals

allograft - tissue transferred between genetically different same-species members

xenograft - tissue transferred between different species

Question 16

What kind of cells mediate graft rejection?

Answer 16

T cells (with CD4+ being more important, both both strongly facilitating rejection

Question 17

True or false: Tissues that are antigenically similar are histocompatible while dissimilar tissues are histoincompatible

Answer 17

TRUE

Question 18

Parent-to-child grafts have a ___ MHC match while siblings have a ___ chance of MHC identity

Answer 18

50% ; 25%

Question 19

The first items to be matched between donor/recipient, and therefore the most intense graft rejections, are caused by…

Answer 19

… blood group Ag differences

Question 20

True or False: Immunosuppressive therapy is only target-specific

Answer 20

FALSE: immunosuppressive therapy can be general or target-specific

Question 21

Sometimes, immune tolerance to __________ is favored due to cells and cytokines found with graft tolerance in these scenarios

Answer 21

allografts (same species, not related)

Question 22

What are immunologically privileged sites?

Answer 22

These are areas where allografts are less likely to experience rejection, such as corneal transplants

Question 23

What is inducing transplantation tolerance?

Answer 23

The idea that cells can get used to each other and generate tolerance before the actual graft takes places (still under study)