Term
| Is central tolerance achieved via negative or positive selection? |
|
Definition
|
|
Term
| What are the different ways peripheral tolerance is achieved? |
|
Definition
| anergy, suppression by Tregs or by limited access of lymphocytes at "immunologically priviledged" sites |
|
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Term
| What are the immunologically priveleged sites? |
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Definition
| brain, cornea and anterior chamber of the eye, testis, and pregnant uterus |
|
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Term
| T/F Autoimmune disease is caused by an innate immune response to normal compoenents of healthy tissue. |
|
Definition
| False, it is an adaptive immune response |
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Term
| What do we think causes autoimmune diseases? |
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Definition
| genetics, gender, environment |
|
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Term
| T/F Autoimmune diseases are the number one leading cause of death in women. |
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Definition
|
|
Term
| What are the three types of autoimmune diseases? |
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Definition
| type II, type III or type IV |
|
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Term
| List some type II autoimmune diseases. |
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Definition
| autoimmune hemolytic anemia, autoimmune thrombocytopenia purpura, Goodpasture's syndrome, pemphigus vulgaris, acute rheumatic fever, Graves' disease, Myasthenia gravis, type 2 diabetes, and hypoglycemia |
|
|
Term
| List some examples of type III autoimmune diseases? |
|
Definition
| subacute bacterial endocarditis, mixed essential cryoglobulinemia, and systemic lupus erythmatosus |
|
|
Term
| List some examples of type IV autoimmune disease. |
|
Definition
| type I diabetes, rheumatoid arthritis, multiple sclerosis |
|
|
Term
| What is autoimmune hemolytic anemia? |
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Definition
| when IgG and IgM bind surface molecules on RBC and activate C' by the classical pathway. This leads to hemolysis via the MAC complex or by phagocytes in the spleen |
|
|
Term
| What is the treatment for patients with anti-neutrophil antibodies? |
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Definition
|
|
Term
| What is Goodpasture's syndrome? |
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Definition
| when IgG is made to the alpha3 chain of type IV collagen (a component of basement membranes) Kidneys are most vulnerable and pts get kidney failure |
|
|
Term
| What is the treatment for Goodpasture's syndrome? |
|
Definition
| plasma exchange and immunosuppressive drugs |
|
|
Term
| What is a common consequence of type III autoimmune diseases? |
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Definition
|
|
Term
| SLE involves making what type of antibodies to what type of antigen? |
|
Definition
| IgG against dsDNA and other common intracellular macromolecules |
|
|
Term
| Reactive arthritis is an example of what type of autoimmune disease? |
|
Definition
|
|
Term
| Why are endocrine glands often targets for AI diseases? |
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Definition
| they are well vascularized and express tissue specific proteins not found elsewhere |
|
|
Term
| Name an example of an AI disease against the adrenal gland. |
|
Definition
|
|
Term
| What causes Graves' disease? |
|
Definition
| autoantibodies against the TSH receptor via a TH2 based response causing the overproduction of thyroid hormone. |
|
|
Term
| Name some unique proteins made by the thyroid gland that are targets for antibodies in AI diseases. |
|
Definition
| thyroglobulin, thyroid peroxidase, TSH receptor, and thyroid iodid transporter |
|
|
Term
| What is the treatment for Graves' disease? |
|
Definition
short-term: drugs that inhibit thyroid function
long-term: thyroidectomy or radioisotope I131 plus daily thyroid hormones |
|
|
Term
| What causes Hashimoto's thyroiditis? |
|
Definition
| when antibodies and effector T cells (Th1) specific for thyroid antigens cause lymphocytes to infiltrate the thyroid and destroy it and form tertiary lymphoid tissue |
|
|
Term
| What's the difference between tertiary and secondary lymphoid tissue? |
|
Definition
| tertiary is not encapsulated and lacks lymphatics |
|
|
Term
| What is the therapy for Hashimoto's thyroiditis? |
|
Definition
| synthetic hormones on a daily basis |
|
|
Term
| Why is a baby often born with symptoms of the mother's AI disease? |
|
Definition
| because mother's IgG can cross the placenta and cause the problem in the baby |
|
|
Term
| What are the antibodies and T cells targeted against in type I diabetes? |
|
Definition
| insulin, glutamic acid decarboxylase and other specialized proteins of the beta cells of the islets of langerhans |
|
|
Term
| What causes myasthenia gravis? |
|
Definition
| autoantibodies that bind to acetylcholine receptors on muscle cells which causes their endocytosis and degradation, lowering the number of surface receptors and decreasing sensitivity to neuronal stimulation |
|
|
Term
| What are the typical early symptoms of myasthenia gravis? |
|
Definition
| droopy eyelids (ptosis) and double vision (diplopia) |
|
|
Term
| What is the treatment for myasthenia gravis? |
|
Definition
| pryidostigmine (inhibitor of cholinesterase which degrades acetylcholine) and the immunosuppressive drug azathoprione |
|
|
Term
| In hypoglycemia does the antibody act as an agonist or an antagonist? |
|
Definition
| it acts as an agonist to the insulin receptor |
|
|
Term
| ALE, rheumatoid arthritis, scleroderma, temporal arteritis, and polymyalgia rheumatica are all examples of ______ AI diseases. |
|
Definition
|
|
Term
| Female:male ratio for rheumatoid arthritis is ____. |
|
Definition
|
|
Term
| How does rheumatoid arthritis usually present? |
|
Definition
| chronic episodic inflammation starting between ages 20-40 |
|
|
Term
| What causes rheumatoid arthritis? |
|
Definition
| stimulation of B cells that make igM, IgG and IgA antibodies specific for the Fc region of human IgG (rheumatoid factor-Rf) |
|
|
Term
| What causes the joint erosion in RA? |
|
Definition
| synovium of affected joints are infiltrated by CD4 and CD8 T cells, PMNs, macrophages, and Rf producing plasma cells. Proinflammatory (TNF alpha, IL1 and Il6) response with activation of macrophages. Secretion of proteinases and collagenases |
|
|
Term
| What are the therapies for RA? |
|
Definition
| traditional antiinflammatory and immunosuppressive drugs (can include prednisone and methotrexate) and newer therapies like infliximab and rituximab |
|
|
Term
|
Definition
| chimeric anti-TNFalpha monoclonal antibody |
|
|
Term
|
Definition
| an antiCD20 monoclonal antibody that destroys 98% of circulating B cells by ADCC dependent mechanism |
|
|
Term
|
Definition
| Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Occurs in people with 2 defective AIRE allels that thereby develope B and T cell autoimmune responses against many different targets. Aka autoimmune polyglandular disease (APD) |
|
|
Term
| Most circulating autoreactive T cells are not usually activated because most cells lack... |
|
Definition
| the B7 costimulatory molecules needed for activation. If activation does occur, the function of B7 is kept "in check" by CTLA-4 which competes with CD28 for B7 |
|
|
Term
| Certain forms of CTLA-4 is associated with which AI diseases? |
|
Definition
| graves, hasimotos and type I diabetes |
|
|
Term
| What characteristics uniquely defines Tregs? |
|
Definition
| regulatory cytokines, expression of CD25 and the use of transcription repressor FoxP3 (specified by a gene on the X chromosome) |
|
|
Term
| CD4+ Tregs that bind to their antigen in the context of MHC class II inhibit neighboring T cells responding to the same autoantigens via which cytokines? |
|
Definition
|
|
Term
| In order for a CD4+ Treg to supress other T cells bound to the same autoantigen, they need what costimulatory signal? |
|
Definition
|
|
Term
|
Definition
| immune dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome due to a rare deficiency in Fox P3 |
|
|
Term
| What is the treatment for IPEX? |
|
Definition
|
|
Term
| Why do we think that women have a much greater relative incidence of autoimmune disease? |
|
Definition
| likely influence of sex steroids and pregnancy results in exacerbation of some AI diseases and remission of others |
|
|
Term
| What is the dominant genetic factor affecting susceptibility to many autoimmune diseases? |
|
Definition
| HLA's peptide presenting function |
|
|
Term
| Pulmonary hemorrhage in Good pasture's syndrome is associated with.. |
|
Definition
| smoking--alveoli are damaged by smoke and lack of tissue integrity allows access of autoantibodies to basement membranes where immune complex deposition and activation of C' lead to burst blood vessels and subsequent hemorrhage |
|
|
Term
| What is sympathetic ophthalmia? |
|
Definition
| when physical trauma to one eye causes immune response to be initiated against intraocular protein antigens. THen effector T cells return via blood stream and attack antigens in both eyes. Tx is removal of damaged eye and immunosuppressive drugs |
|
|
Term
| Name the most simple and well-defined examples of an autoimmune disease that is a by=product of the specific immune response to infectoin. |
|
Definition
|
|
Term
| T/F Immune privilege is due to lack of access of effector cells. |
|
Definition
| False, in sympathetic ophthalmia, trauma to one eye causes an immune response to attack both eyes. This illustrates that immune privilege is due to mechanisms that prevent indction of immune resonse. |
|
|
Term
| What causes rheumatic fever? |
|
Definition
| 2-3 weeks after an infection (usually in the throat) with certain strains of streptococcus pyogenes (group A streptococcus) antibodies specific for the M protein of the bacterial cell wall react with epitopes present on heart, joint and kidney tissue. These activate C' and generate widespread inflammation called rheumatic fever which can sometimes cause heart failure |
|
|
Term
| What is molecular mimicry? |
|
Definition
| the chance antigenic similarity between a pathogen and a cell antigen which results in the induction of antibodies or T cells that act against both pathogen and self |
|
|
Term
| Why are rates of rheumatic fever now lower than they have been in the past? |
|
Definition
| because we treat strep with antibiotics |
|
|
Term
| T/F Rheumatic fever is a transient autoimmune disease. |
|
Definition
| True, CD4 T cells that helped in the antibacterial response are not stimulated by autoantigens so once the bacteria is eradicated, there is no longer an autoimmune response |
|
|
Term
| Type I diabetes is associated with which infections? |
|
Definition
| coxsackie A virus, coxsackie B virus, echoviruses and rubella |
|
|
Term
| Chlamydia trachomatis is associated with what AI disease? |
|
Definition
|
|
Term
| Which HLA types are associated with type 1 diabetes? |
|
Definition
|
|
Term
| What AI disease is Borrelia burgdorferi associated with? |
|
Definition
| chronic arthritis in Lyme disease along with HLA-DR2 and DR4 |
|
|
Term
| What infections are Reactive arthritis associated with? |
|
Definition
| shigella flexneri, salmonella typhimurium, salmonella enteritidis, yersinia enterocolitica, campylobacter jejuni |
|
|
Term
| What are the two ways in which T cells can help cause an AI response? |
|
Definition
they can recognized self antigens as foreign via molecular mimicry
also, AI T cells can be activated in a nonspecific manner by infection which can overcome the anergy that usually supresses them |
|
|
Term
| What is epitope spreading? |
|
Definition
| the process by which an immune response initially targets epitopes in one part of an antigenic molecule but then progresses to other non-cross reactive epitopes on the same antigen |
|
|
Term
| Name examples of epitope spreading. |
|
Definition
| Pemphigus vulgaris and the milder variant, pemphigus foliaceus; SLE; MS; Crohns disease; ulcerative colitis |
|
|
Term
| WHere is the endemic foci of pemphigus foliaceus? |
|
Definition
| brazil (fogo sevagum)--> occurs across all ethnicities in rural areas only and the disease dissapears with urbanization so it is thought to be heavily tied to the environment |
|
|
Term
| The antibody in PF and PV is directed against... |
|
Definition
| Desmoglein is an adhesion molecule present in the desmosomes that "bind" keratinocytes together. Before symptoms, the Abs areagainst the EC5 domain. THen when symptoms start the ab's for EC1 and EC2 appear. |
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