Autoimmune Diseases/ transplantation

Hashimoto’s thyroiditis

antibodies and Th1 cells are specific for the thyroid Ag, this causes a DTH response and the thyroid cannot take up iodine, thyroid starts to grow causes hypothyroidism, and goiter. more common in women

Type 1 diabetes mellitus

beta cells in the pancreas are attacked, CTLs go to pancreas and cause compliment activation, ADCC, NK cells and have a DTH response

Myasthenia Gravis (graves disease)

Hyperactivation of the thyroid, autoantibodies bind acetylcholine receptors and block normal binding this causes lysis and this weakens skeletal muscles

Systemic Lupus erythematosus

type 3 hypersensitivity causes chronic inflammation, auto antibodies go against DNA, histones, and other self structures

multiple sclerosis

autoreactive T cells for inflammatory lesions along the myelin sheaths around nerve fibers in the brain and spinal chord. can lead to neurological disability and paralysis

Rheumatoid arthritis

causes chronic joint inflammation, rheumatoid factors are produced, auto antibodies are reactive with determinates in the Fc region of the IgG and form immune complexes that activate a compliment cascade

Autoimmune Polyendocrine syndrome type-1 (APS-1)

Mutation in the AIRE gene, there is no negative selection of T cells in the thymus

X-linked syndrome IPEX

caused by mutation in the FoxP3 gene, there are no T regulatory cells

Autograft

self tissue grafted to another self area

isograft

transplant between genetically identical individuals ex twins

allograft

tissue transferred between genetically different members of the same species

xenograft

tissue transferred between different species

first set rejection

complete rejection in 12-14 days but memory of the antigraft is generated

second set rejection

occurs much faster within 5-6 days because memory cells were formed

Hyperacute rejection

done by preexisting antibody, happens before graft tissue is revascularized, antibodies bind to graft cells and activate compliment system rejection can happen in 1 day

direct allorecognition

recipients t cell directly bind and attack doner MHC

indirect allorecognition

self APC takes up dead graft cells and presents them to self T cells

chronic rejection Phase

happens months or years after acute rejection stops

lymphoid irradiation

eliminates lymphocytes and is used in bone marrow transplants to treat Graft v host disease, recipient gets x-ray exposure to wipe out the recipiant’s immune cells and donor stem cells can form a new immune system

Azathioprine

mitotic inhibitor that diminishes b and t cell proliferation, increases survival rates of allografts

Cyclophosphamide

inserts into the DNA helix and disrupts it

Cyclosporin A(CsA), FK506, Rapamycin

fungal metabolites inhibit Th cell proliferation and cytokine expression reducing the activation of affecter populations in graft rejection

Monoclonal antibodies to CD3

deplete T cells before transplant

mAb for high affinity IL-2 receptor CD25

block prolifiration of t cells activated in respose to graft aloantigens

mAb aginst CD20

depleate mature B cells

mAb aginst T cell specific markers

have ben used to pretreat donors bone marrow and destroy immunocompetent t cells

CTLA-4 fusion proteins

can induce t cell anergy abatacept (stop t cell activation)