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AUTOIMMUNE DISEASES. Martin Liška. Autoimmune disease. Results from a failure of self-tolerance Immunological tolerance is specific unresponsiveness to an antigen All individuals are tolerant of their own (self) antigens. Autoimmunity. is defined as an immune response against self antigens - PowerPoint PPT Presentation
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AUTOIMMUNE DISEASESAUTOIMMUNE DISEASES
Martin LiškaMartin Liška
Autoimmune diseaseAutoimmune disease
Results from a failure of self-toleranceResults from a failure of self-tolerance Immunological tolerance is specific Immunological tolerance is specific
unresponsiveness to an antigenunresponsiveness to an antigen All individuals are tolerant of their own All individuals are tolerant of their own
(self) antigens(self) antigens
AutoimmunityAutoimmunity
is defined as an immune response against self is defined as an immune response against self antigensantigens
The principal factors in the development of The principal factors in the development of autoimmunity are the inheritance of susceptibility autoimmunity are the inheritance of susceptibility genes and environmental triggers, such as genes and environmental triggers, such as infectionsinfections
Most autoimmune diseases are polygenic and Most autoimmune diseases are polygenic and are asssociated wih multiple gene loci, the most are asssociated wih multiple gene loci, the most important of which are the MHC genesimportant of which are the MHC genes
Infections may activate self-reactive Infections may activate self-reactive lymphocytes, thereby triggering the development lymphocytes, thereby triggering the development of autoimmune diseasesof autoimmune diseases
AUTOIMMUNE PATOLOGICAL AUTOIMMUNE PATOLOGICAL RESPONSE- ETIOLOGYRESPONSE- ETIOLOGY
the diseases arethe diseases are chronic chronic and usually and usually irreversibleirreversible incidence: 5%-7% of population, higher frequencies in incidence: 5%-7% of population, higher frequencies in
women, increases with agewomen, increases with age
factors factors contribute to autoimmunitycontribute to autoimmunity:: - internal- internal (HLA association, polymorphism of cytokine (HLA association, polymorphism of cytokine
genes, defect in genes regulating apoptosis, polymorphism genes, defect in genes regulating apoptosis, polymorphism in genes for TCR a H immunoglobulin chains, association in genes for TCR a H immunoglobulin chains, association with immunodeficiency, hormonal factors) with immunodeficiency, hormonal factors)
- external- external (infection, stress by activation of (infection, stress by activation of neuroendocrine‘s line and hormonal dneuroendocrine‘s line and hormonal dyysbalance, drug and sbalance, drug and ionization through modification of autoantigens)ionization through modification of autoantigens)
CLINICAL CATEGORIESCLINICAL CATEGORIES
systemicsystemic - affect many organs and tissue - affect many organs and tissue
organ localizedorgan localized - affect predominantly one organ - affect predominantly one organ
accompanied by affection of other organs accompanied by affection of other organs (inflammatory bowel diseases, celiac disease, (inflammatory bowel diseases, celiac disease, AI hepatitis, pulmonary fibrosis)AI hepatitis, pulmonary fibrosis)
organ specificorgan specific - affect one organ or group of organs - affect one organ or group of organs
connected withconnected with development or functiondevelopment or function
EXAMPLES OF SYSTEMIC EXAMPLES OF SYSTEMIC AUTOIMMUNE DISEASES AUTOIMMUNE DISEASES
examples examples autoantibodies autoantibodies
SYSTEMIC AUTOIMMUNE DISEASESSYSTEMIC AUTOIMMUNE DISEASES
Systemic lupus erythematosusSystemic lupus erythematosus Rheumathoid arthritisRheumathoid arthritis Sjögren‘s syndromeSjögren‘s syndrome DermatopolymyositisDermatopolymyositis Systemic sclerosisSystemic sclerosis Mixed connective tissue disease Mixed connective tissue disease VasculitisVasculitis
SYSTEMIC LUPUS ERYTHEMATOSUSSYSTEMIC LUPUS ERYTHEMATOSUS
chronic, inflammatory, multiorgan disorderchronic, inflammatory, multiorgan disorder
autoantibodies react with nuclear material and attack autoantibodies react with nuclear material and attack cell function, immune complexes with dsDNA deposit cell function, immune complexes with dsDNA deposit in the tissue in the tissue
general symptoms: general symptoms: include malaise, fever, weight include malaise, fever, weight lossloss
multiple tissuemultiple tissue are involved including the skin, are involved including the skin, mucosa, kidney, joints, brain and cardiovascular mucosa, kidney, joints, brain and cardiovascular systemsystem
characteristic features: characteristic features: butterfly rash, renal butterfly rash, renal involvement, CNS manifestation, pulmonary fibrosisinvolvement, CNS manifestation, pulmonary fibrosis
DIAGNOSTIC TESTSDIAGNOSTIC TESTS
a elevated a elevated ESRESR (erythrocyte sedimentation rate), (erythrocyte sedimentation rate), low low CRPCRP, trombocytopenia, leucopenia, hemolytic anemia, , trombocytopenia, leucopenia, hemolytic anemia, decreased levels of complement compoundsdecreased levels of complement compounds (C4, C3), (C4, C3), elevated serum elevated serum IIg levels, immune complexes in serumg levels, immune complexes in serum
AUTOANTIBODIESAUTOANTIBODIES
Autoantibodies: ANA, dsDNA Autoantibodies: ANA, dsDNA (double-(double-stranded)stranded), ENA, ENA (SS-A/Ro, SS-A/La), Sm, (SS-A/Ro, SS-A/La), Sm, against histones, phospholipidsagainst histones, phospholipids
RHEUMATOID ARTHRITISRHEUMATOID ARTHRITIS
chronic, inflammatory disease with systemic involvementchronic, inflammatory disease with systemic involvement characterized by an inflammatory joint lesion in the synovial characterized by an inflammatory joint lesion in the synovial
membrane, destruction of the cartilage and bone, results in the membrane, destruction of the cartilage and bone, results in the joint deformationjoint deformation
clinical features: arthritis, fever, fatigue, weakness, weight lossclinical features: arthritis, fever, fatigue, weakness, weight loss systemic features: vasculitis, pericarditis, uveitis, nodules under systemic features: vasculitis, pericarditis, uveitis, nodules under
skin, intersticial pulmonary fibrosisskin, intersticial pulmonary fibrosis diagnostic tests: diagnostic tests: elevated C- reactive protein elevated C- reactive protein and ESR, elevated serum gammaglobulin levelsand ESR, elevated serum gammaglobulin levels - - autoantibodies autoantibodies against IgG = rheumatoid factor against IgG = rheumatoid factor ((RFRF), ), a-CCPa-CCP (cyclic citrulline peptid), ANA (cyclic citrulline peptid), ANA - - X-raysX-rays of hands and legs- show a periarticular of hands and legs- show a periarticular porosis, marginal erosionporosis, marginal erosion
SJÖGREN‘S SYNDROMESJÖGREN‘S SYNDROME
chronic inflammatory disease affecting exocrine glandschronic inflammatory disease affecting exocrine glands the primary targetsthe primary targets are the lacrimal and salivary gland duct epitheliumare the lacrimal and salivary gland duct epithelium general featuresgeneral features: malaise, weakness, fever: malaise, weakness, fever primaryprimary syndrome - features: dry eyes and dry mouth, swollen syndrome - features: dry eyes and dry mouth, swollen
salivary glands, dryness of the nose, larynx, bronchi and vaginal salivary glands, dryness of the nose, larynx, bronchi and vaginal mucosa, involvement kidney, central and periferal nervous system, mucosa, involvement kidney, central and periferal nervous system, artarthhritisritis
secondarysecondary syndrome – is associated with others AI diseases (SLE, syndrome – is associated with others AI diseases (SLE, RA, sclerodermia, polymyositis, primary biliary cirhosis,AI thyroiditis) RA, sclerodermia, polymyositis, primary biliary cirhosis,AI thyroiditis)
autoantibodies against ENA autoantibodies against ENA (SS-A, SS-B),(SS-A, SS-B), ANA, RFANA, RF The Schirmer test - measures the production The Schirmer test - measures the production of tearsof tears
Systemic sclerosisSystemic sclerosis
sclerosis in the skin or other organssclerosis in the skin or other organs Diffuse sclerodermaDiffuse scleroderma (progressive systemic (progressive systemic
sclerosis) is the most severe formsclerosis) is the most severe form,, involves skin, will generally cause internal involves skin, will generally cause internal
organ damage (specifically the lungs and organ damage (specifically the lungs and gastrointestinal tractgastrointestinal tract))
The The limited formlimited form is much milder is much milder The limited form is often referred to as The limited form is often referred to as
CREST syndromeCREST syndrome ((CREST is an acronym for CREST is an acronym for the five main features: the five main features: CCalcinosis, alcinosis, RRaynaud's aynaud's syndrome, syndrome, EEsophageal dysmotility, sophageal dysmotility, SSclerodactyclerodactylyly, , TTelangiectasiaelangiectasia
Immunological findingsImmunological findings
ANA, ENA - anti-Scl-70 ANA, ENA - anti-Scl-70 (fluorescence of (fluorescence of nucleolus)nucleolus), anti-centromers, anti-centromers
Mixed connective Mixed connective tissue diseasetissue disease
combines features of polymyositis, systemic combines features of polymyositis, systemic lupus erythematosus, scleroderma, and lupus erythematosus, scleroderma, and dermatomyositis dermatomyositis ((overlap syndromeoverlap syndrome))
Causes : joint pain/swelling, malaise, Causes : joint pain/swelling, malaise, Raynaud phenomenon, muscle inflammation Raynaud phenomenon, muscle inflammation and sclerodactyly (thickening of the skin of and sclerodactyly (thickening of the skin of the pads of the fingers) the pads of the fingers)
Distinguishing laboratory characteristics: Distinguishing laboratory characteristics: a positive, speckled anti-nuclear antibody a positive, speckled anti-nuclear antibody
(ANA) and anti-U1-RNP antibody (ENA)(ANA) and anti-U1-RNP antibody (ENA)
Heliotrope rash is a violaceous eruption on the upper eyelids, often with swelling
• a connective-tissue disease related to polymyositis (PM) that is characterized by inflammation of the muscles and the skin.
Gottron's sign is an erythematous, scaly eruption occurring in symmetric fashion over the MCP and interphalangeal joints
Dermatopolymyositis
DermatopolymyositisDermatopolymyositis
Elevated creatine phosphokinase (CPK)Elevated creatine phosphokinase (CPK)
muscle biopsy (a mixed B- and T-cell muscle biopsy (a mixed B- and T-cell perivascular inflammatory infiltrate, perivascular inflammatory infiltrate, perifascicular muscle fiber atrophy) perifascicular muscle fiber atrophy)
EMG (electromyogram)EMG (electromyogram) autoantibodies autoantibodies - - ENA (Jo-1)ENA (Jo-1)
VasculitisVasculitis
characterized by inflammatory destruction characterized by inflammatory destruction of vessels leading to thrombosis and of vessels leading to thrombosis and
aneurysmaneurysmss pproliferaroliferation of the tion of the intimintimal part of blood-vessel al part of blood-vessel
wall and wall and fibrinoid nefibrinoid necrosiscrosis affect mostly lung, kidneys, skinaffect mostly lung, kidneys, skin
diagnostic tests: diagnostic tests: elevated ESR, CRP, elevated ESR, CRP, leuleuccocytosis, biopsy of affected organ ocytosis, biopsy of affected organ ((necrosis, granulomasnecrosis, granulomas)), angiography, angiography
VasculitisVasculitis
p- ANCA p- ANCA (myeloperoxidase) positivity ((myeloperoxidase) positivity (Polyarteritis Polyarteritis nodosa, Churg- Strauss,nodosa, Churg- Strauss, Microscopic polyarteritis Microscopic polyarteritis nodosa)nodosa)
c- ANCA c- ANCA (serin prote(serin proteininase) positivase) positivee ( (Wegener Wegener granulomatosisgranulomatosis, Churg- Strauss syndrome), Churg- Strauss syndrome)
ClassificationClassification
Large vessel vasculitis (Large vessel vasculitis (Takayasu arteritis, Takayasu arteritis, Giant cell (temporal) arteritis)Giant cell (temporal) arteritis)
Medium vessel vasculitis Medium vessel vasculitis (Polyarteritis nodosa, (Polyarteritis nodosa, Wegener's granulomatosis, Kawasaki disease)Wegener's granulomatosis, Kawasaki disease)
Small vessel vasculitis Small vessel vasculitis (Churg-Strauss (Churg-Strauss arteritis, Microscopic polyarteritis, Henoch-arteritis, Microscopic polyarteritis, Henoch-SchSchöönlein purpura)nlein purpura)
Symptoms:Symptoms: fatigue, weakness, fever, fatigue, weakness, fever, arthralgias, abdominal pain, hypertension, renal arthralgias, abdominal pain, hypertension, renal insufficiency, and neurologic dysfunctioninsufficiency, and neurologic dysfunction
EXAMPLES OF ORGAN- SPECIFIC EXAMPLES OF ORGAN- SPECIFIC AUTOIMMUNE DISEASESAUTOIMMUNE DISEASES
diseasesdiseases autoantibodiesautoantibodies
ORGANOLEPTIC AUTOIMMUNE ORGANOLEPTIC AUTOIMMUNE DISEASESDISEASES
Ulcerative colitisUlcerative colitis Crohn‘s diseaseCrohn‘s disease Autoimmune hepatitisAutoimmune hepatitis Primary biliary cirhosisPrimary biliary cirhosis Pulmonary fibrosisPulmonary fibrosis
Ulcerative colitisUlcerative colitis
chronic inflammation of the large intestine chronic inflammation of the large intestine mucosa and submucosa mucosa and submucosa
features: diarrheafeatures: diarrhea,, blood bloodyy and mucus and mucus stools stools extraintestinal features (artextraintestinal features (arthhritis, uveitis)ritis, uveitis) autoantibodies autoantibodies against against pANCApANCA, a- large , a- large
intestine intestine
Crohn‘s diseaseCrohn‘s disease
the granulomatous inflammation of the granulomatous inflammation of whole whole intestinal wall with ulceration and scarring that intestinal wall with ulceration and scarring that can result in abscess and fistula formationcan result in abscess and fistula formation
the inflammation of Crohn's disease the most the inflammation of Crohn's disease the most commonly affects the terminal ileum, presents commonly affects the terminal ileum, presents with diarrhea and is accompanied by with diarrhea and is accompanied by extraintestinal features - iridocyclitis, uveitis, extraintestinal features - iridocyclitis, uveitis, artritis, spondylitis artritis, spondylitis
antibodies againstantibodies against Saccharomyces Saccharomyces cerevisiaecerevisiae ( (ASCAASCA), a- pancreas), a- pancreas
Primary biliary cirhosisPrimary biliary cirhosis
autoimmune disease of the liver marked by the slow autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts; can lead to progressive destruction of the small bile ducts; can lead to cirrhosiscirrhosis
AMAAMA= antimitochondrial autoantibodies= antimitochondrial autoantibodies
AUTOIMMUNE HEPATITISAUTOIMMUNE HEPATITIS
typetype II – association with autoantibodies against – association with autoantibodies against smooth muscles smooth muscles SMASMA, ANA, ANCA, SLA, ANA, ANCA, SLA
type II –type II – autoantibodies against microsomes autoantibodies against microsomes LKM-1 LKM-1 = liver-kidney microsomes= liver-kidney microsomes
type IIItype III – autoantibodies against – autoantibodies against SLA SLA (solubile liver (solubile liver
antigen)antigen)
type IVtype IV – overlap syndrome with PBC – – overlap syndrome with PBC – autoantibodies against mitochondries autoantibodies against mitochondries AMAAMA
Pulmonary fibrosisPulmonary fibrosis
isis associated with SLE, RA, systemic associated with SLE, RA, systemic sclerosis, polymyositissclerosis, polymyositis
autoantibodies nonspecific- RF, ANAautoantibodies nonspecific- RF, ANA biopsy, biopsy, lung function testinglung function testing, X-ray, X-ray
ORGAN SPECIFIC AUTOIMMUNE ORGAN SPECIFIC AUTOIMMUNE DISEASESDISEASES
Autoimmune endocrinopathyAutoimmune endocrinopathy Autoimmune neurological diseasesAutoimmune neurological diseases Autoimmune cytopeniaAutoimmune cytopenia
AUTOIMMUNE ENDOCRINOPATHYAUTOIMMUNE ENDOCRINOPATHY
Hashimoto‘s thyroiditisHashimoto‘s thyroiditis Graves-Basedow diseaseGraves-Basedow disease Diabetes mellitus I. typeDiabetes mellitus I. type Addison‘s diseaseAddison‘s disease Autoimmune polyglandular syndromeAutoimmune polyglandular syndrome Pernicious anemiaPernicious anemia
Hashimoto‘s thyroiditisHashimoto‘s thyroiditis
thyroid disease result to hypothyroidism on the thyroid disease result to hypothyroidism on the base of lymphocytes and plasma cells infiltratebase of lymphocytes and plasma cells infiltrate
autoantibodies against thyroidal peroxidase (autoantibodies against thyroidal peroxidase (a-a-
TPOTPO) and/or against thyroglobulinu () and/or against thyroglobulinu (a-TGa-TG))
Grave‘s diseaseGrave‘s disease
thyrotoxicosis from overproduction of thyroid thyrotoxicosis from overproduction of thyroid hormone (patient exhibit fatigue, nervousness, hormone (patient exhibit fatigue, nervousness, increased sweating, palpitations, weight loss,increased sweating, palpitations, weight loss,
exophtalmus)exophtalmus)
autoantibodies against autoantibodies against thyrotropinthyrotropin receptor,receptor, autoantibodies cause thyroid cells proliferationautoantibodies cause thyroid cells proliferation
Diabetes mellitus (insulin- Diabetes mellitus (insulin- dependent)dependent)
characterized by an inability to process sugars in characterized by an inability to process sugars in the diet, due to a decrease in or total absence of the diet, due to a decrease in or total absence of insulin production insulin production
results from immunologic destruction of the results from immunologic destruction of the insuline- producing insuline- producing β-cells of the islets of β-cells of the islets of Langerhans in the pancreasLangerhans in the pancreas
autoantibodies against autoantibodies against GADGAD- glutamic acid - glutamic acid decarboxylase = primary antigen), decarboxylase = primary antigen), autoantibodies anti- islet cell, anti- insulin autoantibodies anti- islet cell, anti- insulin
islets are islets are infiltrated with B and T cellsinfiltrated with B and T cells
Polyglandular autoimmune syndromePolyglandular autoimmune syndrome
combination of several different AI combination of several different AI endocrinopathiesendocrinopathies
autoantibodies appear in according with the autoantibodies appear in according with the
connected disordersconnected disorders
Pernicious anemiaPernicious anemia the deficiency of the intrinsic factor results in the deficiency of the intrinsic factor results in
inadequate and abnormal formation of inadequate and abnormal formation of erythrocytes and failure to absorb vitamin B12 erythrocytes and failure to absorb vitamin B12
clinical feature- atrophic gastritis, macrocytic clinical feature- atrophic gastritis, macrocytic anemiaanemia
autoantibodies against autoantibodies against parietal cells of gastric parietal cells of gastric mucosemucose, against intrinsic factor (transportation , against intrinsic factor (transportation of B12 vitamin)of B12 vitamin)
AUTOIMMUNE NEUROPATHYAUTOIMMUNE NEUROPATHY
Guillain-Barré syndrome (acute idiopathic Guillain-Barré syndrome (acute idiopathic polyneuritis)polyneuritis)
Myasthenia gravisMyasthenia gravis
Multiple sclerosisMultiple sclerosis
Guillain-Barré syndromeGuillain-Barré syndrome
inflammation demyelinateinflammation demyelinatess peripheral neuropathy that peripheral neuropathy that causes progressive muscle weakness and paralysiscauses progressive muscle weakness and paralysis
the cause is the loss of myelinthe cause is the loss of myelin occurs often 1-3 weeks after infection occurs often 1-3 weeks after infection
(Campylobacter jej.) (Campylobacter jej.)
featuresfeatures:: progressive weakness and paresthesia of progressive weakness and paresthesia of the lower and later upper extremitas and respiratory the lower and later upper extremitas and respiratory muscles, weakness can leads to paralysis and muscles, weakness can leads to paralysis and respiratory failure respiratory failure
immunologic findings: autoantibodies against immunologic findings: autoantibodies against ganglioside ganglioside membranemembrane
Myasthenia gravisMyasthenia gravis
chronic disease with impaired neuromuscular chronic disease with impaired neuromuscular transmissiontransmission
characterized by muscle weakness and fatigue characterized by muscle weakness and fatigue the muscle weakness and neuromuscular the muscle weakness and neuromuscular
dysfunction result from blockage and depletion dysfunction result from blockage and depletion of acetylcholine receptors at the myoneural of acetylcholine receptors at the myoneural junctionjunction
immunological findings: autoantibodies against immunological findings: autoantibodies against Ach receptorsAch receptors
ptosis of the eyeptosis of the eye
Multiple sclerosisMultiple sclerosis
chronic demyelichronic demyelininizing disease with abnormal reaction zing disease with abnormal reaction T T cells to cells to myeline protein on the base of mimicry between a myeline protein on the base of mimicry between a virus and myeline proteinvirus and myeline protein
features: weakness, ataxia, impaired vision, urinary features: weakness, ataxia, impaired vision, urinary bladder dysfunction, paresthesias, mental abberations bladder dysfunction, paresthesias, mental abberations
autoantibodies against MOGautoantibodies against MOG (myelin-oligodendrocyte (myelin-oligodendrocyte glycoprotein) glycoprotein)
Magnetic resonanceMagnetic resonance imaging of the brain and spine imaging of the brain and spine shows areas of demyelination shows areas of demyelination
The cerebrospinal fluid is tested for The cerebrospinal fluid is tested for oligoclonal bandsoligoclonal bands, , can provide evidence of chronic inflammation of the can provide evidence of chronic inflammation of the central nervous system central nervous system
AUTOIMMUNE CYTOPENIAAUTOIMMUNE CYTOPENIA
AI hemolytic diseaseAI hemolytic disease- autoantibodies - autoantibodies against membrane erythrocyte antigens against membrane erythrocyte antigens
AI trombocytopeniaAI trombocytopenia - autoantibodies against - autoantibodies against
trombocyte antigens (GPIIb/IIIa) trombocyte antigens (GPIIb/IIIa)
AI neutropeniaAI neutropenia - autoantibodies against - autoantibodies against membrane neutrofil antigensmembrane neutrofil antigens
IMMUNOSUPPRESSIONIMMUNOSUPPRESSION
non-specific treatmentnon-specific treatmentexamples of drugsexamples of drugsindicationindicationrisksrisks
ImmunosuppressantsImmunosuppressants
Drugs that inhibit or prevent activity of the immune Drugs that inhibit or prevent activity of the immune systemsystem
They are used in immunosuppressive therapy to:They are used in immunosuppressive therapy to: Prevent the rejectionPrevent the rejection of transplanted organs and of transplanted organs and
tissues (bone marrow, heart, kidney, liver) tissues (bone marrow, heart, kidney, liver) Treat Treat autoimmune diseasesautoimmune diseases or diseases that are or diseases that are
most likely of autoimmune origin (rheumatoid arthritis, most likely of autoimmune origin (rheumatoid arthritis, multiple sclerosis, myasthenia gravis, systemic lupus multiple sclerosis, myasthenia gravis, systemic lupus erythematosus, Crohn's disease, pemphigus, erythematosus, Crohn's disease, pemphigus, ulcerative colitis). ulcerative colitis).
Treat some other Treat some other non-autoimmune inflammatorynon-autoimmune inflammatory diseasesdiseases (allergic asthma, atopic eczema). (allergic asthma, atopic eczema).
GlucocorticoidsGlucocorticoids
suppress the cell-mediated immunity- act by suppress the cell-mediated immunity- act by inhibiting genes that code for various cytokines inhibiting genes that code for various cytokines (e.g.IL-2)(e.g.IL-2)
decreasedecrease cytokine production reduces the T cytokine production reduces the T cell proliferation.cell proliferation.
suppress the humoral immunity, causing B suppress the humoral immunity, causing B cells to express smaller amounts of IL-2 and cells to express smaller amounts of IL-2 and IL-2 receptors- this diminishes both B cell clone IL-2 receptors- this diminishes both B cell clone expansion and antibody synthesis.expansion and antibody synthesis.
GlucocorticoidsGlucocorticoids leads to diminished eicosanoid production, leads to diminished eicosanoid production,
supsupppression of the cyclooxygenase expression ression of the cyclooxygenase expression Glucocorticoids also stimulate the lipocortin-1 Glucocorticoids also stimulate the lipocortin-1
escaping to the extracellular space, where it binds to escaping to the extracellular space, where it binds to the leuthe leuccocyte membrane receptors and inhibits : ocyte membrane receptors and inhibits : epithelial adhesion, migration, chemotaxis, epithelial adhesion, migration, chemotaxis, phagocytosis, respiratory burst, and the release of phagocytosis, respiratory burst, and the release of various inflammatory mediators from neutrophils, various inflammatory mediators from neutrophils, macrophages, and mastocytes.macrophages, and mastocytes.
side-effectsside-effects: hypertension, dyslipidemia, : hypertension, dyslipidemia, hyperglycemia, peptic ulcers, osteoporosis, disturbed hyperglycemia, peptic ulcers, osteoporosis, disturbed growth in childrengrowth in children
Drugs affecting the Drugs affecting the proliferation of both T cells and proliferation of both T cells and B cellsB cells
CyclophosphamideCyclophosphamide -very efficient in the -very efficient in the therapy of therapy of systemic lupus erythematosus, systemic lupus erythematosus, autoimmune hemolytic anemiasautoimmune hemolytic anemias
high doses cause pancytopenia and high doses cause pancytopenia and hemorrhagic cystitishemorrhagic cystitis
MethotrexateMethotrexate is a folic acid antagonist, acts is a folic acid antagonist, acts during DNA and RNA synthesis, and thus it is during DNA and RNA synthesis, and thus it is cytotoxic during the S-phase of the cell cycle; cytotoxic during the S-phase of the cell cycle; used in the treatment of autoimmune diseases used in the treatment of autoimmune diseases ((RA, Crohn's diseaseRA, Crohn's disease) and in transplantations.) and in transplantations.
Drugs affecting the Drugs affecting the proliferation of both T cells and proliferation of both T cells and B cellsB cells
AzathioprineAzathioprine is a purine synthesis inhibitor, is a purine synthesis inhibitor, inhibiting the proliferation of cells, especially inhibiting the proliferation of cells, especially leuleuccocytes; SLE, RA, sclerosis multiplex, ocytes; SLE, RA, sclerosis multiplex, transplantationtransplantation
Mycophenolate mofetilMycophenolate mofetil – affects the enzyme – affects the enzyme that controls the purine synthesisthat controls the purine synthesis
Used in transplantation of solid organUsed in transplantation of solid organ
Drugs blocking the Drugs blocking the activation of lymphocytesactivation of lymphocytes TacrolimusTacrolimus - prevents the cell from transitioning from - prevents the cell from transitioning from
the Gthe G00 into G into G11 phase of the cell cycle phase of the cell cycle Used to prevent rejection reactions, atopic eczemaUsed to prevent rejection reactions, atopic eczema
Cyclosporin A-Cyclosporin A- inhibits calcineurin, which is inhibits calcineurin, which is responsible for activating the transcription of interleukin-responsible for activating the transcription of interleukin-2; inhibits cytokines production and interleukin release 2; inhibits cytokines production and interleukin release
Used to prevent rejection reactionsUsed to prevent rejection reactions
Side effectsSide effects: nephrotoxicity, neurotoxicity, : nephrotoxicity, neurotoxicity, hypertension, dyslipidemia, hyperglycemiahypertension, dyslipidemia, hyperglycemia
Monoclonal antibodiesMonoclonal antibodies
Monoclonal antibodies are directed towards Monoclonal antibodies are directed towards exactly defined antigensexactly defined antigens
DaclizumabDaclizumab - acts by binding the IL-2a - acts by binding the IL-2a receptor's α chain, preventing the IL-2 induced receptor's α chain, preventing the IL-2 induced clonal expansion of activated lymphocytes and clonal expansion of activated lymphocytes and shortening their survivalshortening their survival
used in the prophylaxis of the acute organ used in the prophylaxis of the acute organ rejection after the bilateral kidney rejection after the bilateral kidney transplantationtransplantation
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