chapter 16 Flashcards
What is tolerance?
prevention of an immune response against self antigens
-deletion of lymphocytes before they mature
-takes place in generative lymphoid organs
Central Tolerance
-either renders self-reactive lymphocytes nonresponsive or actively generates inhibiting lymphocytes
-occurs outside bone marrow and thymus
peripheral tolerance
high affinity for self antigen results in induction of __________in B and T cells
apoptosis
Describe how B cells have been shown to undergo receptor editing:
-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
peripheral tolerance regulates __________________in the circulation.
autoreactive cells
Dependent mechanisms occur as Treg cells express high levels of inhibitory __________________molecules.
CTLA-4
Independent mechanisms rely upon secretion of ___________________________into the surrounding area, shutting down nearby cells’ responses.
cytokines (IL-10, TGF-β, IL-35)
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 ___________________
linked supression
Autoimmunity is caused by?
failure of tolerance processes
-may be organ-specific or systemic
-may involve antibodies, T cells, immune complexes, or any combination of elements
What is the mechanism for Hashimoto’s thyroiditis?
Autoantibodies and sensitized TH1 cells specific for thyroid Ag
are produced
Describe the effects of Hashimoto’s thyroiditis:
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
What causes Type 1 diabetes mellitus?
Caused by autoimmune attack against insulin-producing beta cells
in the pancreas
What is the mechanism for Type 1 diabetes mellitus?
– 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
What is the mechanism for Myasthenia gravis?
Autoantibodies that bind acetylcholine receptors on motor
end plates of muscles
What are the effects of Myasthenia gravis?
– Block the normal binding of acetylcholine, induce complement-mediated lysis of cells
– Result is a progressive weakening of the skeletal muscles
How do we treat Myasthenia gravis?
increasing acetylcholine levels, decreasing Ab production, and/or removing Ab
What are the organ specific diseases?
Hashimoto’s thyroiditis
Type 1 diabetes mellitus
Myasthenia gravis
What is the mechanism for Systemic lupus erythematosus?
Auto-Ab against DNA, histones, other self structures
Symptoms of lupus result from specificity of Ab produced and can include:
– Fever, weakness, arthritis, skin rashes, and kidney dysfunction
– Type III hypersensitivity reactions often induce damage
What are some factors of Rheumatoid arthritis?
» Auto-Ab reactive with determinants in the Fc region of
IgG
» Form immune complexes and activate complement
cascades
What are several possible mechanisms have been proposed for the induction of autoimmunity?
– 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
autograft
self tissue grafted to another self area (skin grafts, blood vessels)
isograft
transplant between genetically identical individuals (inbred strains of mice, identical twins)
allograft
tissue transferred between genetically different members of the same species (majority of transplant cases)
xenograft
tissue transferred between different species (baboon heart into a human)
describe specificity and memory in allograft rejection:
- 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
What cells mediate graft rejection?
CD4+ T cells seem to be more important than CD8+, but both together strongly facilitate rejection
Siblings have a ____% chance of MHC identitiy.
25
parent-to-child grafts have a ____% MHC match due to always having one MHC haplotype in common
50
how do blood group antigen differences play a role in graft tolerance?
-most intense graft rejections
-they are the first items to be matched between donor/recipient
describe the sensitization stage of graft rejection:
-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
describe the effector stage of graft rejection:
– 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
describe specific immunosuppressive therapy:
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
immunologically privileged sites:
-Allografts in such areas are less likely to experience rejection
- Corneal transplants are highly successful
What is the current idea for inducing transplantation tolerance?
-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
