module d bold terms Flashcards
autoimmunity
failure of central and peripheral tolerance to prevent negative selection or inactivation of the adaptive immune system (failure to recognize self as self)
autoimmune diseases linked to genetic polymorphisms and mutations in CTLA4
-insulin-dependent (type 1) diabetes mellitus
-graves disease
-hashimoto disease
-systemic lupus erythematosus
goodpasture syndrome
-autoimmune disease that causes vasculitis and can be worsened by cigarette smoke
-type II hypersensitivity caused by the destruction of the basement membranes of the kidneys and lungs resulting in tissue damage and vasculitis
guillain-barre syndrom
caused by campylobactor jejuni which mimics host cell proteins
molecular mimicry
infectious agent mimics the host cell proteins and can cause autoimmunity
insulin-dependent (type 1) diabetes mellitus
-pancreatic beta cells in the islets of langerhans are targeted
-beta cells secrete insulin
-over 50 genes and some environmental factors have been identified
-autoantibodies target insulin, glutamate decarboxylase, and IA-2, which are specific to pancreatic beta cells
graves disease
-thyroid specific autoantibodies bind to the TSH receptor on thyroid epithelial cells
-autoantibodies act as agonists and mimic normal TSH binding
-T3 and T4 are continuously released and the basal metabolic rate is increased
-symptoms include heat intolerance, weight loss, excessive sweating, and warm skin
hyperthyroidism
the basal metabolic rate of the thyroid is increased
hypothyroidism
the thyroid is destroyed and the basal metabolic rate is decreased
hashimoto disease, hashimoto thyroiditis
-thyroid specific autoantibodies that can recognize thyroid peroxidase, thyroglobulin, and TSH receptor
-autoantibodies can mediate antibody-dependent cell-mediated cytotoxicity of thyroid cells causing hypothyroidism
-common symptoms include fatigue, weight gain, hair loss, dry skin, and sensitivity to cold
autoantibody
an antibody produced against the hosts own tissues
agonists
mimic the effect of the regular ligand
antagonists
prevent the activity and signaling of receptors
myasthenia gravis
antagonist autoantibodies also bind to acetylcholine receptors preventing the activity and signaling of the receptors (agonist)
rheumatoid arthritis
-autoimmune response causes chronic inflammation of the joints
-large percentage of patients produce rheumatoid factor
-autoantibodies from immune complexes containing soluble IgG or IgM, and the immune complexes deposit in joints and drive inflammation through a type III hypersensitivity-like response
rheumatoid factor
anti-immunoglobulin antibodies capable of recognizing the Fc region of IgG or IgM
multiple sclerosis (ms)
-systemic autoimmune disease
-symptoms are due to the targeted destruction of myelin-producing cells of the nervous system and impaired neuronal function
-symptoms include muscle weakness, vision problems, and coordination problems
blood transfusion
involves the transfer of blood cells or blood-cell components from individual (donor) to another (recipient)
Jean-Baptiste Denys
-1667, french physician
-first recorded successful blood transfusion into a human
-introduced sheep’s blood into a 15-year old boy
Karl Landsteiner
-1901
-discovered A, B, and O blood types
-different blood types were incompatible and mixing them would cause an immune response that destroyed the donor red blood cells
autograft
-transplant tissue from area to another from the same individual
-most similar
isograft
-tissue transplantation between genetically identical individuals
-2nd most similar
allograft
-tissue transplantation between genetically distinct individual
-most common
-3rd most similar, 2nd most different
xenograft
-tissue transplantation between different species
-can be tolerated short term (5-10 years) but not long term
-4th most similar, most different
alloantigens
antigens that differ between individuals of the same species
transplantation rejection
occurs when the recipient’s immune system targets donor tissue alloantigens
immunosuppressive
immune system is suppressed
georges mathe
-1958
-performed first bone marrow transplant
-treated patients who had been exposed to radioactivity due to a nuclear power plant accident
Robert Good
-1968
-successfully treated an immunodeficiency with a bone marrow transplant
john kersey
-1975
-first to successfully use a bone marrow transplant to treat lymphoma
hematopoietic cell genetic abnormalities
mutations in critical genes can affect blood cell development and function
erythroid lineage
thalassemia and sickle cell anemia
lymphoid lineage
immunodeficiencies
alloreactions
follow solid organ and hematopoietic stem cell transplantations caused by polymorphisms in HLA molecules
graft-versus-host disease
newly transplanted hematopoietic system recognizes recipient’s tissues and organs as non-self and targets them in an immune respons
hyperacute rejection
-caused by preexisting antibodies in the recipient that bind to blood antigens or HLA molecules expressed on blood vessels within transplanted tissue
-mirrors a type II hypersensitivity reaction
-preventable by proper blood type matching HLA typing/crossmatching
acute rejection
-caused by recognition of donor MHC-peptide complexes presented by donor dendritic cells to recipient T cells
-mirrors a type IV (delayed-type) hypersensitivity reaction
-preventable by proper HLA typing and crossmatiching and use of immunosuppressive drugs
chronic rejection
-occurs months or years later after transplantation and is the cause for why a transplanted organ ultimately fail
-caused by immune responses that target the vasculature of the transplanted organ
-mirrors a type IV (delayed type) hypersensitivity reaction
-cannot be prevented by immunosuppressive drugs
minor histocompatibility antigens
ex) H-Y antigens
direct pathway of allorecognition
donor dendritic cells migrate from inflamed transplanted tissue to secondary lymphoid tissues and present alloantigens via donor MHC molecules to recipient T cells
indirect pathway of allorecognition
-driven by donor cells in transplanted tissue that undergo apoptosis due to inflammation and ischemia
-apoptotic donor cells are phagocytosed by recipient dendritic cells, which then migrate to secondary lymphoid tissue
semidirect pathway of allorecognition
involves the exchange of intact donor MHC class I molecules with recipient dendritic cells
cyclosporin a
blocks t cell activation by binding to cyclophilins and inhibiting calcineurin activation
cyclophilins
bound by cyclosporin a to block t cell activation by inhibiting calcineurin activation
FK-binding proteins
bound by FK-506 to block t cell activation by inhibiting calcineurin activation
graft-versus-leukemia effect
-increased risk of cancer recurrence in leukemia patients when mature t cells are removed from donor bone marrow prior to transplant
-mature t cells present in the transplanted bone marrow target and destroy residual leukemia cells that have survived chemotherapy and irradiation
-effect supplemented by donor NK cells that are re-educated after transplant to recognize leukemia cells in the recipient
cancer
-results from abnormal or uncontrolled cell growth
-changes in cell growth are driven by mutation in DNA or from infections that modify cell growth proteins
angiogensis
-cancer cells gain access to nutrients and oxygen through increased blood vessel growth
metastasis
cancer cells leave a primary site of growth and migrate to other organs and tissues
benign tumor
can typically be removed by surgery because they are encapsulated and localized with defined borders
malignant tumor
more difficult to treat because they have undefined borders and may have already spread to other parts of the body
leukemia
cancer is caused by hematopoietic cells
lymphoma
cancer that affects lymphoid tissue
myeloma
cancer that affects bone marrow
sarcoma
cancer that is derived from connective tissues
tumor suppressor genes or proto-oncogenes
mutations allow cells to undergo uncontrolled cellular division
tumor-associated antigens
overexpressed or inappropriately expressed proteins in tumor cells
tumor-specific antigens
antigens are expressed exclusively by the tumor cells and may be virus encoded proteins
immunosurveillance
the ability of the immune system to target and destroy mutated or tumor cells
