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Terms in this set (45)
what is autoimmunity? why do autoimmune reactions persist?
autoimmune mechanisms underlie many diseases - organ specific or systemic in distribution - genetic factors can play a role
autoimmune responses persist once initiated -inciting self antigen cannot be cleared without complete destruction of the target tissue
what are the two important contributors in an autoimmune. reaction?
autoantibodies and autoreactive T cells
what is the threat from destruction of organ/tissue in an autoimmune reaction?
self antigen cannot be cleared until total destruction of target tissue
classify the two types of autoimmune diseases and give examples
1. organ specific
2. non organ specific
organ specific: brain(ms), thyroid(hashimotos), muscle(myasynthia gravis), stomach(pernicious anemia), adrenal(addisons), pancreas(insulin dependent dm)
non organ specific: muscle(dermatomyositis), kidney(SLE), skin(scleroderma,SLE), joints(rheumatoid arthritis)
what are the changes in thyroid gland as a result of Hashimoto's thyroiditis? what are its symptoms?
involves production of autoantibodies -- leads to goiter or hypothyroidism and upper lid retraction - infiltration of glands with inflammatory lymphoid cells including mononuclear phagocytes, lymphocytes and plasma cells
colloid is lost
what are the two main targets for autoantibodies in hashimotos thyroiditis?
what are the two main consequences of hashimotos thyroiditis?
goiter and hypothyroidism.
what is. graves disease and. its characteristic features?
over production of thyroid hormone - causes enlargement of thyroid gland -- causes other symptoms such as exophthalmos, heat intolerance and anxiety
identify thyroid diseases that involve thyroid destruction., stimulation of thyroid hormone synthesis
thyroid destruction - hashimotos thyroiditis, hashs p goiter, hashitoxicosis, primary. myxadema
synthesis - graves disease, non goitrous hyperthyroid, hashitoxicosis
what type of disorders is SLE? what is the target of SLE antibodies in a tissue?
SLE=systemic lupus erthyematosus -- a systemic disorder -- serum from disorder targets many tissues in the body -- one dominant antibody targets cell nucleus
what are the common ocular manifestations of SLE?
keratoconjunctivitis sicca, blepharitis, chalazion, retinal vasculatitis is an internal manifestation
give some examples of diseases where autoimmune conditions can coexist
chance of developing another. autoimmune disease is high with an existing condition -- 15% of patients with primary Sjogren's syndrome ..concomitant autoimmune hypothyroidism -- 30% of patients with SLE and Sjogren's syndrome.. second, third or even fourth autoimmune disease --- high frequency of thyroid antibodies occur in patients w/ pernicious anemia
what are the ocular manifestations of myasthenia gravis and. rheumatoid arthritis?
mya grave-ptosis and diplopia
ra-scleritis, dry eye, and uveitis
identify. the autoantibodies existing in bronchial asthma and guillian barre syndrome
bronchial asthma-autoantiodies to alpha adrenergic receptors
gullain barre-sodium channel autoantibodies
what are the two major types of dry eye? how do cytokines influence inflammation in dry eye?
aqueous deficient and evaporative
dry eye pts have alot of inflammatory cytokines in their tear fluid, including TNF-alpha and INF-gamma which indicate classical TH1 response
what are the common cytokines found in patients with dry eye? pts with allergic conjunctivitis?
IL-1, IL-6, IL-8
what are the two common subsets of T cells and their cytokine secretions?
T helper 1 cells-TH1 -- produce interferon gamma (IFN-gamma) and tumor necrosis factor-alpha
T helper 2 cells-TH2 -- produce interleukin 4 (IL-4), IL-5 and IL-13
explain the sequence of events involved in dry eye mediated inflammation involving APCs and T cells
T cells are activated by recognizing antigen in the context of MHC class II molecules on antigen presenting cells such. as. macrophages -- antigen presenting cells infiltrate the inflamed tissue toward the end of the acute response -- APCs engulf the foreign antigen, process it into peptides, and present the peptides in the context of their MHC class II molecules -- then presented to T cells -- T cells are activated --(differentiation of CD4+ T cells into TH1 and TH2 is dependent on cytokine expression at site of injury) -- typically due to desiccating nature of dry eye setting, more likely TH1 inducing environment
what are the two pathways activated in type 1 hypersensitivity response and the end products of the pathways?
antigen enters body and. binds igE, second exposure can activate mast cells -- this results in either
-granule release of performed mediators(results in histamine and ish??) OR
-phospholipase A released from mast cell membrane(results in thromboxane A or prostoglandins or leukotrine?)
name some common mediators released due to activation of mast cells. what are the two main phases involved in type 1 hypersensitivity response and. their main effects.
histamine and cytokines
sensitization phase and activation phase -- immediate hypersensitivity
what are the two main. mechanisms of immunopathological damage in type. 2 hypersensitivity reaction?
when the antigen is. localized in a particular organ ---
-classical complement pathway
-antibody. dependent cell cytotoxicity (ADCC)
disease autoimmune hemmolytic anemia
what is the mechanism. involved in type III. hypersensitivity reaction? name 2 diseases involving this mechanmism.
leads to inflammation through complement activation and phagocyte recruitment
RA(directly stimulates cytokine TNFa)
what is the mechanism involved in Type IV hypersensitivity reaction? Identify a disease involving this mechanism.
delayed type, CD4+ cells respond to tissue antigens by secreting cytokines stimulating inflammation and active phagocytosis, injuring tissue in some dz, CD8+ directly kill tissue cells
type 1 insulin dependent diabetes
what are the two influential factors in autoimmune disease?
explain adn give an example of how genetic factors can play a role in manifestation of additional autoimmune disorders
families with ra are likely to develop others..
organ specific autoimmunity---organ specific autoantibodies
specify the chromosome number and location of MHC region that contributes to disease susceptibility in several. autoimmune diseases
autoimmune diseases tend to be associated wtih particular. HLA specificities
MHC region located on chromosome 6
what is the HLA gene associated with. ankylosing. spondylitis?
single HLA genes-HLA B27
name some autoimmune diseases associated with PTPN22
(genes outside of the HLA region)...
type 1 diabetes and RA
briefly. explain the stages during progression of autoimmune disease
1-predisposition by genes or other factors
2-initiation by. event or environmental trigger (infection, uv light..loss of tolerance and autoantibody regulation)
3-tissue damage from autoimmune attack(further release of self antigens...clinical manifestation of disease)
briefly explain the autoimmune mechanism involving APCs and B cells?
-complex of autoantigen and autoantibody. taken up by APC
-peptides derived from idiotypic segment are presented to the TH cells
-B. cells that express the pathogenic autoantibody can. capture. the complex and receive T cell help via presentation of processed Id to TH cell
-autoreactive B. cells proliferate and produce
identify the sequential events involved in induction of autoimmunity by microbial antigens
naive TH cells fail to recognize autoantigen on a tissue cell due to low concentration or low affinity
--can be overcome by a. cross reacting microbial antigen at higher concentration OR with higher innate affinity together with a costimulator such. as B7
how do cross-reactive foreign antigens induce autoantibody production?
cross reactive microbial antigens stimulate autoreactive lymphocytes -- microbe bearing antigens can cross react with the. cryptic epitopes -- loading of professional APCs with peptides.. sufficient to activate. the naive autoreactive T cells
how is direct stimulation of autoreactive cells by foreign antigen achieved? give an example
antigens or another stimulator can directly trigger autoreactive receptor cells -
examples: direct b cell stimulation adn lipopolysachharide epstein barr virus
what is the influence of infection in an autoimmune disease? give an example
infxs can trigger autoimmune disease relapse
Chronic Staphylococcus aureus nasal carriage
what is the gene influencing cytokines that is implicated in autoimmune disease?
how can introduction of a transgene induce an autoimmune reaction? Give an example
introduction of a transgene for interferong (IFN g ) into pancreatic b -islet cells - upregulation of MHC class II genes if the gene for IFN g is fully expressed
can lead to autoimmune destruction of the islet cells
what class of MHC molecules is implicated in Grave's disease?
MHC class II.
what changes occur during myasthenia gravis? give examples
acetyl choline. receptors. are blocked on teh post synaptic. membrane of the neuromuscular jx
results in muscle weakness and fatigue
what do autoantibodies target in bronchial asthma and Guillain-Barre syndrome?
bronchial. asthma - alpha. adrenergic
guillan barre - sodium channels
describe the mechanism involved in development of pernicious anemia?
autoantibody interferes. with the normal uptake of vitamin B12. -- B12 reacts with intrinsic factor -- but autoantibody binds to intrinsic factor therefore B12. cant get absorbed
how do autoantibodies bring about the damage in rheumatoid arthritis?
erosion of cartilage and bone mediated by. macrophages and fibroblasts
Immune complexes and neutrophils (PMNs) are detectable in the joint space and in the extra-articular tissues
how is pernicious anemia and myasthenia gravis controlled metabolically?
anemia treated by injected B12
myasthenia gravis is treated with administration of cholinesterase inhibitors
what are the two approaches of targeting B cells in SLE?
molecules which target APC mediated stim of T- cells, targeting of T cells using peptide or direct stimulation by anti CD-20 and CD-22 antibodies, target IL-10 with antibodies
what are the four biological agents used to target TNF
what are the targets of Rituximab, toclizumab, abatacept and anakinra? Give their application
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