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96-504: C3b's ability to perform these important functions derives from its ability to covalently bind to the surface of invading pathogens within an organism's body. The cleavage of C3 leaves C3b with an exposed thioester bond, allowing C3b to effectively coat and tag foreign cells by covalently binding to hydroxyl (-OH) and amine (-NH2) groups on foreign cell surfaces. This cleavage can occur via three mechanisms ( classical pathway , alternative pathway and lectin pathway ) that ultimately lead to

192-403: A linear combination of atomic orbitals is performed first, followed by filling of the resulting molecular orbitals with electrons. The two approaches are regarded as complementary, and each provides its own insights into the problem of chemical bonding. As valence bond theory builds the molecular wavefunction out of localized bonds, it is more suited for the calculation of bond energies and

288-470: A buildup of apoptotic debris can be observed in GC because of an ineffective clearance of apoptotic cells. Close to TBM, follicular dendritic cells (FDC) are localised in GC, which attach antigen material to their surface and, in contrast to bone marrow -derived DC, neither take it up nor present it via MHC molecules. Autoreactive B cells can accidentally emerge during somatic hypermutation and migrate into

384-546: A cSLE-like disorders. )(Note that mutations in the UNC93B1 gene may cause either cSLE or the chilblain lupus erythematosus form of cSLE. ) Mutations in a wide range of other genes do not by themselves cause SLE but two or more of them may act together, act in concert with environmental factors, or act in some but not other populations (e.g., cause SLE in Chinese but not Europeans) to cause SLE or an SLE-like syndrome but do so in only

480-457: A definitive diagnosis is reached. Common initial and chronic complaints include fever , malaise , joint pains , muscle pains , and fatigue . Because these symptoms are so often seen in association with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms, however, they are considered suggestive. While SLE can occur in both males and females, it

576-442: A full (or closed) outer electron shell. In the diagram of methane shown here, the carbon atom has a valence of four and is, therefore, surrounded by eight electrons (the octet rule ), four from the carbon itself and four from the hydrogens bonded to it. Each hydrogen has a valence of one and is surrounded by two electrons (a duet rule) – its own one electron plus one from the carbon. The numbers of electrons correspond to full shells in

672-456: A host-cell surface, regulators of complement activity (RCAs), a group of genetically-, structurally-, and functionally-related proteins, inactivate the complement component. Given the C3 is constantly being turned over in the alternative pathway and its ability to rapidly amplify a signal, these proteins are important in regulating the temporal and spatial effects of C3b to infected tissues. An example RCA

768-495: A lesser degree, etc.; thus a "co-valent bond", in essence, means that the atoms share " valence ", such as is discussed in valence bond theory . In the molecule H 2 , the hydrogen atoms share the two electrons via covalent bonding. Covalency is greatest between atoms of similar electronegativities . Thus, covalent bonding does not necessarily require that the two atoms be of the same elements, only that they be of comparable electronegativity. Covalent bonding that entails

864-473: A low serum level of vitamin D ) often occurs in patients with SLE and that its level is particularly low in patients with more active SLE. Furthermore, 5 studies reported that SLE patients treated with vitamin D had significant reductions in the activity of their disease. However, other studies have found that the levels of vitamin D in SLE are not low, that vitamin D does not reduce their SLE's activity, and/or that

960-458: A mixture of atoms and ions. On the other hand, simple molecular orbital theory correctly predicts Hückel's rule of aromaticity, while simple valence bond theory incorrectly predicts that cyclobutadiene has larger resonance energy than benzene. Although the wavefunctions generated by both theories at the qualitative level do not agree and do not match the stabilization energy by experiment, they can be corrected by configuration interaction . This

1056-432: A more severe form of SLE termed childhood-onset systemic lupus erythematosus . The cause of SLE is not clear. It is thought to involve a combination of genetics and environmental factors . Among identical twins , if one is affected there is a 24% chance the other one will also develop the disease. Female sex hormones , sunlight, smoking, vitamin D deficiency , and certain infections are also believed to increase

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1152-463: A person's risk. The mechanism involves an immune response by autoantibodies against a person's own tissues. These are most commonly anti-nuclear antibodies and they result in inflammation . Diagnosis can be difficult and is based on a combination of symptoms and laboratory tests. There are a number of other kinds of lupus erythematosus including discoid lupus erythematosus , neonatal lupus , and subacute cutaneous lupus erythematosus . There

1248-607: A population shift towards immature B cells. Memory B cells with increased CD27 +/ IgD —are less susceptible to immunosuppression. CD27-/IgD- memory B cells are associated with increased disease activity and renal lupus. T cells, which regulate B-cell responses and infiltrate target tissues, have defects in signaling, adhesion, co-stimulation, gene transcription, and alternative splicing. The cytokines B-lymphocyte stimulator (BLyS), also known as B-cell activating factor (BAFF), interleukin 6, interleukin 17, interleukin 18, type I interferons, and tumor necrosis factor α (TNFα) are involved in

1344-437: A positive test for antiphospholipid antibodies; the combination of such findings have earned the term " lupus anticoagulant -positive". Another autoantibody finding in SLE is the anti-cardiolipin antibody , which can cause a false positive test for syphilis . SLE may cause pericarditis (inflammation of the outer lining surrounding the heart), myocarditis (inflammation of the heart muscle), or endocarditis (inflammation of

1440-411: A pro-inflammatory form of cell death, is increased in T lymphocytes, due to mitochondrial dysfunction, oxidative stress, and depletion of ATP. Impaired clearance of dying cells is a potential pathway for the development of this systemic autoimmune disease . This includes deficient phagocytic activity, impaired lysosomal degradation, and scant serum components in addition to increased apoptosis . SLE

1536-508: A regular hexagon exhibiting a greater stabilization than the hypothetical 1,3,5-cyclohexatriene. In the case of heterocyclic aromatics and substituted benzenes , the electronegativity differences between different parts of the ring may dominate the chemical behavior of aromatic ring bonds, which otherwise are equivalent. Certain molecules such as xenon difluoride and sulfur hexafluoride have higher co-ordination numbers than would be possible due to strictly covalent bonding according to

1632-653: A result have impaired degradation of internalized apoptotic debris, which results in chronic activation of Toll-like receptors and permeabilization of the phagolysosomal membrane, allowing activation of cytosolic sensors. In addition, intact apoptotic debris recycles back to the cell membrane and accumulate on the surface of the cell. Recent research has found an association between certain people with lupus (especially those with lupus nephritis ) and an impairment in degrading neutrophil extracellular traps (NETs). These were due to DNAse1 inhibiting factors, or NET protecting factors in people's serum, rather than abnormalities in

1728-761: A result of treating the disease. It can rarely present with intracranial hypertension syndrome , characterized by an elevated intracranial pressure , papilledema , and headache with occasional abducens nerve paresis , absence of a space-occupying lesion or ventricular enlargement, and normal cerebrospinal fluid chemical and hematological constituents. More rare manifestations are acute confusional state , Guillain–Barré syndrome , aseptic meningitis , autonomic disorder , demyelinating syndrome , mononeuropathy (which might manifest as mononeuritis multiplex ), movement disorder (more specifically, chorea ), myasthenia gravis , myelopathy , cranial neuropathy and plexopathy . Neurological disorders contribute to

1824-704: A significant percentage of morbidity and mortality in people with lupus. As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates. One aspect of this disease is severe damage to the epithelial cells of the blood–brain barrier . In certain regions, depression affects up to 60% of women with SLE. Up to one-third of patients report that their eyes are affected. The most common diseases are dry eye syndrome and secondary Sjögren's syndrome , but episcleritis , scleritis , retinopathy (more often affecting both eyes than one), ischemic optic neuropathy , retinal detachment , and secondary angle-closure glaucoma may occur. In addition,

1920-420: A single Lewis structure is insufficient to explain the electron configuration in a molecule and its resulting experimentally-determined properties, hence a superposition of structures is needed. The same two atoms in such molecules can be bonded differently in different Lewis structures (a single bond in one, a double bond in another, or even none at all), resulting in a non-integer bond order . The nitrate ion

2016-447: A small percentage of cases. The development of a genetically-regulated trait or disorder that is dependent on the inheritance of two or more genes is termed oligogenic inheritance or polygenic inheritance . SLE is regarded as a prototype disease due to the significant overlap in its symptoms with other autoimmune diseases. Patients with SLE have higher levels of DNA damage than normal subjects, and several proteins involved in

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2112-435: A threat to the tolerization of B cells and T cells. Dendritic cells in the germinal center may endocytose such antigenic material and present it to T cells, activating them. Also, apoptotic chromatin and nuclei may attach to the surfaces of follicular dendritic cells and make this material available for activating other B cells that may have randomly acquired self-protein specificity through somatic hypermutation. Necrosis,

2208-533: Is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common symptoms include painful and swollen joints , fever , chest pain , hair loss , mouth ulcers , swollen lymph nodes , feeling tired , and a red rash which is most commonly on the face. Often there are periods of illness, called flares , and periods of remission during which there are few symptoms. Children up to 18 years old develop

2304-470: Is associated with defects in apoptotic clearance, and the damaging effects caused by apoptotic debris. Early apoptotic cells express "eat-me" signals, of cell-surface proteins such as phosphatidylserine, that prompt immune cells to engulf them. Apoptotic cells also express find-me signals to attract macrophages and dendritic cells. When apoptotic material is not removed correctly by phagocytes, they are captured instead by antigen-presenting cells, which leads to

2400-400: Is coated in antibodies ( IgG and IgM ) released by B cells . The C1 complement complex binds to these antibodies resulting in its activation via cross proteolysis. This activated C1 complex cleaves C4 and C2 forming a C4bC2b complex that covalently bonds to the surface of the microbe and functions as a C3 convertase, binding and cleaving C3 into C3a and C3b. Binding of a C3b molecule to

2496-423: Is defined as where g | n , l , m l , m s ⟩ A ( E ) {\displaystyle g_{|n,l,m_{l},m_{s}\rangle }^{\mathrm {A} }(E)} is the contribution of the atomic orbital | n , l , m l , m s ⟩ {\displaystyle |n,l,m_{l},m_{s}\rangle } of

2592-493: Is denoted as the covalency of the A−B bond, which is specified in the same units of the energy ⁠ E {\displaystyle E} ⁠ . An analogous effect to covalent binding is believed to occur in some nuclear systems, with the difference that the shared fermions are quarks rather than electrons. High energy proton -proton scattering cross-section indicates that quark interchange of either u or d quarks

2688-468: Is done by combining the valence bond covalent function with the functions describing all possible ionic structures or by combining the molecular orbital ground state function with the functions describing all possible excited states using unoccupied orbitals. It can then be seen that the simple molecular orbital approach overestimates the weight of the ionic structures while the simple valence bond approach neglects them. This can also be described as saying that

2784-449: Is for joint pain , with the small joints of the hand and wrist usually affected, although all joints are at risk. More than 90 percent of those affected will experience joint or muscle pain at some time during the course of their illness. Unlike rheumatoid arthritis , lupus arthritis is less disabling and usually does not cause severe destruction of the joints. Fewer than ten percent of people with lupus arthritis will develop deformities of

2880-669: Is found far more often in women, and the symptoms associated with each sex are different. Females tend to have a greater number of relapses , a low white blood cell count , more arthritis , Raynaud syndrome , and psychiatric symptoms . Males tend to have more seizures , kidney disease , serositis (inflammation of tissues lining the lungs and heart), skin problems , and peripheral neuropathy . As many as 70% of people with lupus have some skin symptoms. The three main categories of lesions are chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. People with discoid lupus may exhibit thick, red scaly patches on

2976-400: Is found to be highly effective. Covalent bond A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms . These electron pairs are known as shared pairs or bonding pairs . The stable balance of attractive and repulsive forces between atoms, when they share electrons , is known as covalent bonding. For many molecules ,

C3b - Misplaced Pages Continue

3072-508: Is membrane cofactor protein (MCP; CD46), which is ubiquitously expressed and plays a critical role in protecting host cells from damage by the C3b. Furthermore, host cells express p33 (globular C1q receptor) on the surface, which binds C1q, and prevents it from initiating complement activation. Due to the importance of C3b, disruptions resulting in deficiencies or up regulation of C3b generation can have serious implications for human health. For example,

3168-403: Is no cure for SLE, but there are experimental and symptomatic treatments. Treatments may include NSAIDs , corticosteroids , immunosuppressants , hydroxychloroquine , and methotrexate . Although corticosteroids are rapidly effective, long-term use results in side effects. Alternative medicine has not been shown to affect the disease. Men have higher mortality. SLE significantly increases

3264-683: Is one of the most difficult challenges in medicine, because it can involve so many different patterns of symptoms, some of which may be mistaken for signs of infectious disease or stroke. A common neurological disorder people with SLE have is headache , although the existence of a specific lupus headache and the optimal approach to headache in SLE cases remains controversial. Other common neuropsychiatric manifestations of SLE include cognitive disorder , mood disorder , cerebrovascular disease , seizures , polyneuropathy , anxiety disorder , psychosis , depression , and in some extreme cases, personality disorders. Steroid psychosis can also occur as

3360-408: Is one such example with three equivalent structures. The bond between the nitrogen and each oxygen is a double bond in one structure and a single bond in the other two, so that the average bond order for each N–O interaction is ⁠ 2 + 1 + 1 / 3 ⁠ = ⁠ 4 / 3 ⁠ . [REDACTED] In organic chemistry , when a molecule with a planar ring obeys Hückel's rule , where

3456-498: Is the dominant process of the nuclear force at short distance. In particular, it dominates over the Yukawa interaction where a meson is exchanged. Therefore, covalent binding by quark interchange is expected to be the dominating mechanism of nuclear binding at small distance when the bound hadrons have covalence quarks in common. Systemic lupus erythematosus Lupus , formally called systemic lupus erythematosus ( SLE ),

3552-527: Is the occurrence of SLE symptoms in an infant born from a mother with SLE, most commonly presenting with a rash resembling discoid lupus erythematosus , and sometimes with systemic abnormalities such as heart block or enlargement of the liver and spleen . Neonatal lupus is usually benign and self-limited. Medications for treatment of SLE can carry severe risks for female and male reproduction. Cyclophosphamide (also known as Cytoxan), can lead to infertility by causing premature ovarian insufficiency (POI),

3648-720: The macrophage activation syndrome . Mutations in about 40 genes have been reported to cause cSLE and/or a cSLE-like disease. These genes include 5 which as of February, 2024 were classified as inborn errors of immunity genes, i.e., DNASE1L3 , TREX1 , IFIH1 , Tartrate-resistant acid phosphatase and PRKCD and 28 other genes, i.e., NEIL3 , TMEM173 , ADAR1 , NRAS , SAMHD1 , SOS1 , FASLG , FAS receptor gene , RAG1 , RAG2 , DNASE1 , SHOC2 , KRAS , PTPN11 , PTEN , BLK , RNASEH2A , RNASEH2B , RNASEH2C , Complement component 1qA , Complement component 1qB , Complement component 1r , Complement component 1s , Complement component 2 , Complement component 3 , UNC93B1 , and

3744-510: The mantle zone , autoreactive B cells require further survival signals from autoreactive helper T cells, which promote the maturation of autoantibody-producing plasma cells and B memory cells. In the presence of autoreactive T cells , a chronic autoimmune disease may be the consequence. Anti-nRNP autoantibodies to nRNP A and nRNP C initially targeted restricted, proline -rich motifs . Antibody binding subsequently spread to other epitopes . The similarity and cross-reactivity between

3840-615: The octet rule . This is explained by the three-center four-electron bond ("3c–4e") model which interprets the molecular wavefunction in terms of non-bonding highest occupied molecular orbitals in molecular orbital theory and resonance of sigma bonds in valence bond theory . In three-center two-electron bonds ("3c–2e") three atoms share two electrons in bonding. This type of bonding occurs in boron hydrides such as diborane (B 2 H 6 ), which are often described as electron deficient because there are not enough valence electrons to form localized (2-centre 2-electron) bonds joining all

3936-705: The pleurae known as pleurisy , which can rarely give rise to shrinking lung syndrome involving a reduced lung volume. Other associated lung conditions include pneumonitis , chronic diffuse interstitial lung disease , pulmonary hypertension , pulmonary emboli , and pulmonary hemorrhage . Painless passage of blood or protein in the urine may often be the only presenting sign of kidney involvement. Acute or chronic renal impairment may develop with lupus nephritis , leading to acute or end-stage kidney failure . Because of early recognition and management of SLE with immunosuppressive drugs or corticosteroids, end-stage renal failure occurs in less than 5% of cases; except in

C3b - Misplaced Pages Continue

4032-465: The C4bC2b complex (C4b2b3b) results in the formation of a C5 convertase, which cleaves C5 into C5a and C5b. C5b associates with C6 , C7 , C8 , and C9 , all of which form a complex that results in a pore through the pathogen's membrane. This pore disrupts the ionic and osmotic balance provided by the pathogen's membrane, and leads to the death of the pathogen cell. In the alternative pathway, C3, present in

4128-668: The DNAse1 itself. DNAse1 mutations in lupus have so far only been found in some Japanese cohorts. The clearance of early apoptotic cells is an important function in multicellular organisms. It leads to a progression of the apoptosis process and finally to secondary necrosis of the cells if this ability is disturbed. Necrotic cells release nuclear fragments as potential autoantigens , as well as internal danger signals, inducing maturation of dendritic cells (DCs) since they have lost their membranes' integrity. Increased appearance of apoptotic cells also stimulates inefficient clearance. That leads to

4224-459: The ability to form three or four electron pair bonds, often form such large macromolecular structures. Bonds with one or three electrons can be found in radical species, which have an odd number of electrons. The simplest example of a 1-electron bond is found in the dihydrogen cation , H 2 . One-electron bonds often have about half the bond energy of a 2-electron bond, and are therefore called "half bonds". However, there are exceptions: in

4320-432: The atom A to the total electronic density of states ⁠ g ( E ) {\displaystyle g(E)} ⁠ of the solid where the outer sum runs over all atoms A of the unit cell. The energy window ⁠ [ E 0 , E 1 ] {\displaystyle [E_{0},E_{1}]} ⁠ is chosen in such a way that it encompasses all of the relevant bands participating in

4416-986: The atoms together, but generally, there are negligible forces of attraction between molecules. Such covalent substances are usually gases, for example, HCl , SO 2 , CO 2 , and CH 4 . In molecular structures, there are weak forces of attraction. Such covalent substances are low-boiling-temperature liquids (such as ethanol ), and low-melting-temperature solids (such as iodine and solid CO 2 ). Macromolecular structures have large numbers of atoms linked by covalent bonds in chains, including synthetic polymers such as polyethylene and nylon , and biopolymers such as proteins and starch . Network covalent structures (or giant covalent structures) contain large numbers of atoms linked in sheets (such as graphite ), or 3-dimensional structures (such as diamond and quartz ). These substances have high melting and boiling points, are frequently brittle, and tend to have high electrical resistivity . Elements that have high electronegativity , and

4512-400: The atoms. However the more modern description using 3c–2e bonds does provide enough bonding orbitals to connect all the atoms, so that the molecules can instead be classified as electron-precise. Each such bond (2 per molecule in diborane) contains a pair of electrons which connect the boron atoms to each other in a banana shape, with a proton (the nucleus of a hydrogen atom) in the middle of

4608-629: The black population, where the risk is many times higher. The histological hallmark of SLE is membranous glomerulonephritis with "wire loop" abnormalities. This finding is due to immune complex deposition along the glomerular basement membrane , leading to a typical granular appearance in immunofluorescence testing. Neuropsychiatric syndromes can result when SLE affects the central or peripheral nervous system . The American College of Rheumatology defines 19 neuropsychiatric syndromes in systemic lupus erythematosus. The diagnosis of neuropsychiatric syndromes concurrent with SLE (now termed as NPSLE),

4704-441: The blood stream, spontaneously cleaves at low rates into C3b and C3a. If a microbe is present, the C3b component will covalently bind to the surface of foreign invader. It then associates with Factor B, which is cleaved by Factor D into Factor Bb. This C3bBb convertase is stabilized by properdin (Factor P) preferentially on microbial surfaces over normal host surfaces, and is now able to cleave many more C3 molecules thus amplifying

4800-737: The bond covalency can be provided in this way. The mass center ⁠ c m ( n , l , m l , m s ) {\displaystyle cm(n,l,m_{l},m_{s})} ⁠ of an atomic orbital | n , l , m l , m s ⟩ , {\displaystyle |n,l,m_{l},m_{s}\rangle ,} with quantum numbers ⁠ n , {\displaystyle n,} ⁠ ⁠ l , {\displaystyle l,} ⁠ ⁠ m l , {\displaystyle m_{l},} ⁠ ⁠ m s , {\displaystyle m_{s},} ⁠ for atom A

4896-430: The bond, sharing electrons with both boron atoms. In certain cluster compounds , so-called four-center two-electron bonds also have been postulated. After the development of quantum mechanics, two basic theories were proposed to provide a quantum description of chemical bonding: valence bond (VB) theory and molecular orbital (MO) theory . A more recent quantum description is given in terms of atomic contributions to

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4992-438: The bond. If the range to select is unclear, it can be identified in practice by examining the molecular orbitals that describe the electron density along with the considered bond. The relative position ⁠ C n A l A , n B l B {\displaystyle C_{n_{\mathrm {A} }l_{\mathrm {A} },n_{\mathrm {B} }l_{\mathrm {B} }}} ⁠ of

5088-440: The case of dilithium , the bond is actually stronger for the 1-electron Li 2 than for the 2-electron Li 2 . This exception can be explained in terms of hybridization and inner-shell effects. The simplest example of three-electron bonding can be found in the helium dimer cation, He 2 . It is considered a "half bond" because it consists of only one shared electron (rather than two); in molecular orbital terms,

5184-455: The cell nucleus . These antibody attacks are the immediate cause of SLE. SLE is a chronic inflammatory disease believed to be a type III hypersensitivity response with potential type II involvement. Reticulate and stellate acral pigmentation should be considered a possible manifestation of SLE and high titers of anti-cardiolipin antibodies , or a consequence of therapy. People with SLE have intense polyclonal B-cell activation, with

5280-587: The connected atoms which determines the chemical polarity of the bond. Two atoms with equal electronegativity will make nonpolar covalent bonds such as H–H. An unequal relationship creates a polar covalent bond such as with H−Cl. However polarity also requires geometric asymmetry , or else dipoles may cancel out, resulting in a non-polar molecule. There are several types of structures for covalent substances, including individual molecules, molecular structures , macromolecular structures and giant covalent structures. Individual molecules have strong bonds that hold

5376-605: The contributions of the magnetic and spin quantum numbers are summed. According to this definition, the relative position of the A levels with respect to the B levels is where, for simplicity, we may omit the dependence from the principal quantum number ⁠ n {\displaystyle n} ⁠ in the notation referring to ⁠ C n A l A , n B l B . {\displaystyle C_{n_{\mathrm {A} }l_{\mathrm {A} },n_{\mathrm {B} }l_{\mathrm {B} }}.} ⁠ In this formalism,

5472-505: The developing world are unclear. Lupus is Latin for 'wolf': the disease was so-named in the 13th century as the rash was thought to appear like a wolf's bite. SLE is one of several diseases known as " the great imitator " because it often mimics or is mistaken for other illnesses. SLE is a classical item in differential diagnosis , because SLE symptoms vary widely and come and go unpredictably. Diagnosis can thus be elusive, with some people having unexplained symptoms of SLE for years before

5568-706: The development of antinuclear antibodies. Monocytes isolated from whole blood of people with SLE show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBMs), which are found in the germinal centres of lymph nodes , even show a definitely different morphology; they are smaller or scarce and die earlier. Serum components like complement factors, CRP , and some glycoproteins are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient. Macrophages during SLE fail to mature their lysosomes and as

5664-413: The disease or a side effect of pharmacological treatment. People with SLE may have an association with antiphospholipid antibody syndrome (a thrombotic disorder), wherein autoantibodies to phospholipids are present in their serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged partial thromboplastin time (which usually occurs in hemorrhagic disorders) and

5760-503: The drug. The VigiBase drug safety data repositor diagnosed 12,166 cases of drug-induced SLE recorded between 1968 and 2017. Among the 118 agents causing SLE, five main classes were most often associated with drug-induced SLE. These drugs were antiarrhythmic agents such as procainamide or quinidine ; antihypertensive agents such as hydralazine , captopril , or acebutolol ; antimicrobial agents such as minocycline , isoniazid , carbamazepine , or phenytoin ; and agents that inhibit

5856-422: The electronic density of states. The two theories represent two ways to build up the electron configuration of the molecule. For valence bond theory, the atomic hybrid orbitals are filled with electrons first to produce a fully bonded valence configuration, followed by performing a linear combination of contributing structures ( resonance ) if there are several of them. In contrast, for molecular orbital theory

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5952-412: The feasibility and speed of computer calculations compared to nonorthogonal valence bond orbitals. Evaluation of bond covalency is dependent on the basis set for approximate quantum-chemical methods such as COOP (crystal orbital overlap population), COHP (Crystal orbital Hamilton population), and BCOOP (Balanced crystal orbital overlap population). To overcome this issue, an alternative formulation of

6048-410: The formation of a C3 convertase. Formation of a C3 convertase functions as a positive feedback loop, so as more C3b is cleaved, more C3 convertases are formed, further amplifying the signal on the surface of the microbial invader. This amplification of signal serves as a powerful tool for the immune system in effective clearance of the invading pathogen. In the classical pathway, the microbial pathogen

6144-419: The germinal center light zone. Autoreactive B cells, maturated coincidentally, normally do not receive survival signals by antigen planted on follicular dendritic cells and perish by apoptosis. In the case of clearance deficiency, apoptotic nuclear debris accumulates in the light zone of GC and gets attached to FDC. This serves as a germinal centre survival signal for autoreactive B-cells. After migration into

6240-400: The greater the value of ⁠ C A , B , {\displaystyle C_{\mathrm {A,B} },} ⁠ the higher the overlap of the selected atomic bands, and thus the electron density described by those orbitals gives a more covalent A−B bond. The quantity ⁠ C A , B {\displaystyle C_{\mathrm {A,B} }} ⁠

6336-467: The hands and feet. People with SLE are at particular risk of developing osteoarticular tuberculosis . A possible association between rheumatoid arthritis and SLE has been suggested, and SLE may be associated with an increased risk of bone fractures in relatively young women. Anemia is common in children with SLE and develops in about 50% of cases. Low platelet count ( thrombocytopenia ) and low white blood cell count ( leukopenia ) may be due to

6432-430: The inflammation-inducing actions of interferon or tumor necrosis factor . Discoid (cutaneous) lupus is limited to skin symptoms and is diagnosed by biopsy of rash on the face, neck, scalp or arms. Approximately 5% of people with DLE progress to SLE. SLE is triggered by environmental factors that are unknown. In SLE, the body's immune system produces antibodies against self-protein , particularly against proteins in

6528-604: The inflammatory process and are potential therapeutic targets. SLE is associated with low C3 levels in the complement system . Tingible body macrophages (TBMs) – large phagocytic cells in the germinal centers of secondary lymph nodes  – express CD68 protein. These cells normally engulf B cells that have undergone apoptosis after somatic hypermutation . In some people with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present

6624-523: The inner lining of the heart). The endocarditis of SLE is non-infectious, and is also called Libman–Sacks endocarditis . It involves either the mitral valve or the tricuspid valve . Atherosclerosis also occurs more often and advances more rapidly than in the general population. Steroids are sometimes prescribed as an anti-inflammatory treatment for lupus; however, they can increase one's risk for heart disease, high cholesterol, and atherosclerosis. SLE can cause pleuritic pain as well as inflammation of

6720-467: The liver, where the C3b-tagged immune complex is then destroyed. In both cases C3b interacts with the C3b receptor, complement receptor 1 on phagocytic cells, such as macrophages and neutrophils , allowing for engulfment of the pathogen. Furthermore, erythrocytes with Cr1 on their surface bind and deliver the immune complexes to the mononuclear phagocyte system via interactions with C3b. The key to

6816-612: The loss of normal function of one's ovaries prior to age forty. Methotrexate can cause termination or deformity in fetuses and is a common abortifacient , and for men taking a high dose and planning to father, a discontinuation period of 6 months is recommended before insemination. Fatigue in SLE is probably multifactorial and has been related to not only disease activity or complications such as anemia or hypothyroidism , but also to pain , depression , poor sleep quality, poor physical fitness and lack of social support . Some studies have found that vitamin D deficiency (i.e.,

6912-413: The mass center of | n A , l A ⟩ {\displaystyle |n_{\mathrm {A} },l_{\mathrm {A} }\rangle } levels of atom A with respect to the mass center of | n B , l B ⟩ {\displaystyle |n_{\mathrm {B} },l_{\mathrm {B} }\rangle } levels of atom B is given as where

7008-441: The maturation of DCs and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules. Autoimmunity possibly results from the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation and

7104-430: The medication that triggered the episode is stopped. While there are no established criteria for diagnosing drug-induced SLE, most authors have agreed on the following definition: the afflicted patient had a sufficient and continuing exposure to the drug, at least one symptom compatible with SLE, no history suggestive of SLE before starting the drug, and resolution of symptoms within weeks or months after stopping intake of

7200-653: The medications used to treat SLE can cause eye disease: long-term glucocorticoid use can cause cataracts and secondary open-angle glaucoma, and long-term hydroxychloroquine treatment can cause vortex keratopathy and maculopathy . While most pregnancies have positive outcomes, there is a greater risk of adverse events occurring during pregnancy. SLE causes an increased rate of fetal death in utero and spontaneous abortion (miscarriage). The overall live-birth rate in people with SLE has been estimated to be 72%. Pregnancy outcome appears to be worse in people with SLE whose disease flares up during pregnancy. Neonatal lupus

7296-403: The neutrophils and likely plays a critical role in disease progression. The absence of regulatory proteins, resulting in excessive C3 activation and C3b formation, is associated with diseases such as atypical hemolytic uremic syndrome (aHUS), hemolytic disorders, and certain autoimmune disorders . In such cases treatment with the complement-inhibitory anti-C5 monoclonal antibody, eculizumab ,

7392-458: The number of π electrons fit the formula 4 n  + 2 (where n is an integer), it attains extra stability and symmetry. In benzene , the prototypical aromatic compound, there are 6 π bonding electrons ( n  = 1, 4 n  + 2 = 6). These occupy three delocalized π molecular orbitals ( molecular orbital theory ) or form conjugate π bonds in two resonance structures that linearly combine ( valence bond theory ), creating

7488-432: The preservation of genomic stability show polymorphisms , some of which increase the risk for SLE development. Defective DNA repair is a likely mechanism underlying lupus development. Drug-induced lupus erythematosus is a (generally) reversible condition that usually occurs in people being treated for a long-term illness. Drug-induced lupus mimics SLE. However, symptoms of drug-induced lupus generally disappear once

7584-453: The production of autoantibodies by plasma cells is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in people with cutaneous lupus erythematosus (CLE). In healthy conditions, apoptotic lymphocytes are removed in germinal centers (GC) by specialized phagocytes, the tingible body macrophages (TBM), which is why no free apoptotic and potential autoantigenic material can be seen. In some people with SLE,

7680-427: The quantum theory of the atom; the outer shell of a carbon atom is the n  = 2 shell, which can hold eight electrons, whereas the outer (and only) shell of a hydrogen atom is the n  = 1 shell, which can hold only two. While the idea of shared electron pairs provides an effective qualitative picture of covalent bonding, quantum mechanics is needed to understand the nature of these bonds and predict

7776-537: The risk of cardiovascular disease , with this being the most common cause of death. While women with lupus have higher risk pregnancies, most are successful. Rate of SLE varies between countries from 20 to 70 per 100,000. Women of childbearing age are affected about nine times more often than men. While it most commonly begins between the ages of 15 and 45, a wide range of ages can be affected. Those of African , Caribbean , and Chinese descent are at higher risk than those of European descent . Rates of disease in

7872-517: The same fertilized egg ) and genome-wide association studies have identified numerous genes that by themselves promote the development of SLE, particularly childhood-onset SLE, i.e., cSLE, in rare cases of SLE/cSLE. The single-gene (also termed monogenic) causes of cSLE (or a cSLE-like disorder) develop in individuals before they reach 18 years of age. cSLE typically is more severe and potentially lethal than adult-onset SLE because it often involves SLE-induced neurologic disease, renal failure, and/or

7968-708: The sharing of electron pairs between atoms (and in 1926 he also coined the term " photon " for the smallest unit of radiant energy). He introduced the Lewis notation or electron dot notation or Lewis dot structure , in which valence electrons (those in the outer shell) are represented as dots around the atomic symbols. Pairs of electrons located between atoms represent covalent bonds. Multiple pairs represent multiple bonds, such as double bonds and triple bonds . An alternative form of representation, not shown here, has bond-forming electron pairs represented as solid lines. Lewis proposed that an atom forms enough covalent bonds to form

8064-572: The sharing of electrons allows each atom to attain the equivalent of a full valence shell, corresponding to a stable electronic configuration. In organic chemistry, covalent bonding is much more common than ionic bonding . Covalent bonding also includes many kinds of interactions, including σ-bonding , π-bonding , metal-to-metal bonding , agostic interactions , bent bonds , three-center two-electron bonds and three-center four-electron bonds . The term covalent bond dates from 1939. The prefix co- means jointly, associated in action, partnered to

8160-661: The sharing of electrons over more than two atoms is said to be delocalized . The term covalence in regard to bonding was first used in 1919 by Irving Langmuir in a Journal of the American Chemical Society article entitled "The Arrangement of Electrons in Atoms and Molecules". Langmuir wrote that "we shall denote by the term covalence the number of pairs of electrons that a given atom shares with its neighbors." The idea of covalent bonding can be traced several years before 1919 to Gilbert N. Lewis , who in 1916 described

8256-546: The signal. Incorporation of an additional C3b into the C3bBb C3 convertase leads to the formation of C3Bb3b C5 convertase. Once cleaved C3b can either generate C3 or C5 convertases , as mentioned above, or else covalently bind to the microbial surface, tagging the cell for phagocytosis in a process known as opsonization. Additionally, C3b molecules can attach to the Fc regions of antigen-bound antibodies leading to phagocytosis or movement to

8352-530: The simple molecular orbital approach neglects electron correlation while the simple valence bond approach overestimates it. Modern calculations in quantum chemistry usually start from (but ultimately go far beyond) a molecular orbital rather than a valence bond approach, not because of any intrinsic superiority in the former but rather because the MO approach is more readily adapted to numerical computations. Molecular orbitals are orthogonal, which significantly increases

8448-453: The skin. Similarly, subacute cutaneous lupus manifests as red, scaly patches of skin but with distinct edges. Acute cutaneous lupus manifests as a rash. Some have the classic malar rash (commonly known as the butterfly rash ) associated with the disease. This rash occurs in 30–60% of people with SLE. Hair loss , mouth and nasal ulcers, and lesions on the skin are other possible manifestations. The most commonly sought medical attention

8544-406: The strongest covalent bonds and are due to head-on overlapping of orbitals on two different atoms. A single bond is usually a σ bond. Pi (π) bonds are weaker and are due to lateral overlap between p (or d) orbitals. A double bond between two given atoms consists of one σ and one π bond, and a triple bond is one σ and two π bonds. Covalent bonds are also affected by the electronegativity of

8640-531: The structures and properties of simple molecules. Walter Heitler and Fritz London are credited with the first successful quantum mechanical explanation of a chemical bond ( molecular hydrogen ) in 1927. Their work was based on the valence bond model, which assumes that a chemical bond is formed when there is good overlap between the atomic orbitals of participating atoms. Atomic orbitals (except for s orbitals) have specific directional properties leading to different types of covalent bonds. Sigma (σ) bonds are

8736-482: The success of the complement system in clearing antigens is regulating the effects of C3b to pathogens alone and not healthy, host cells. This is done through several different mechanisms. One mechanism, mentioned above, is the stabilization of the C3bBb convertase by properdin preferentially on microbial surfaces, not on host surfaces, a step necessary for formation of a functional C3 convertase. Furthermore, if C3b does bind to

8832-715: The third electron is in an anti-bonding orbital which cancels out half of the bond formed by the other two electrons. Another example of a molecule containing a 3-electron bond, in addition to two 2-electron bonds, is nitric oxide , NO. The oxygen molecule, O 2 can also be regarded as having two 3-electron bonds and one 2-electron bond, which accounts for its paramagnetism and its formal bond order of 2. Chlorine dioxide and its heavier analogues bromine dioxide and iodine dioxide also contain three-electron bonds. Molecules with odd-electron bonds are usually highly reactive. These types of bond are only stable between atoms with similar electronegativities. There are situations whereby

8928-586: The two complement component 4 genes , C4A and C4B . (The C4A and C4B genes code respectively for complement component A and complement component B proteins. These two proteins combine to form the complement component 4 protein which plays various roles in regulating immune function. Individuals normally have multiple copies of the C4A and C4B gene but if they have reduced levels of one and/or both of these genes make low levels of complement component 4 protein and thereby are at risk for developing cSLE or

9024-746: The uncontrolled cleavage of C3b is associated with the disease C3 glomerulopathy, in which deposits of C3 in the glomeruli disrupt kidney function and can eventually result in kidney failure. Patients with diseases associated with elevated levels of immune complexes such as systemic lupus erythematosus , leprosy , and AIDS are found to have significantly decreased levels of the C3b receptor, Cr1, expression on erythrocytes, as well as altered expression of Cr1 on neutrophils in response to stimulation. Healthy neutrophils increase their Cr1 expression tenfold in response to chemoattractant peptides. However, patients with diseases such as AIDS do not display this response to stimulation, which results in reduced phagocytosis by

9120-552: The understanding of reaction mechanisms . As molecular orbital theory builds the molecular wavefunction out of delocalized orbitals, it is more suited for the calculation of ionization energies and the understanding of spectral absorption bands . At the qualitative level, both theories contain incorrect predictions. Simple (Heitler–London) valence bond theory correctly predicts the dissociation of homonuclear diatomic molecules into separate atoms, while simple (Hartree–Fock) molecular orbital theory incorrectly predicts dissociation into

9216-1086: The vitamin D levels and responses to vitamin D treatment varied in different patient populations (i.e., varied based on whether the study was conducted on individuals living in Africa or Europe). Because of these conflicting findings, the following middle ground has been proposed for using vitamin D to treat SLE: a) patients with SLE that have 25-hydroxyvitamin D 2 plus 25-hydroxyvitamin D 3 serum levels less than 30 ng/ml should be treated with vitamin D to keep these levels at or above 30 ng/ml or, in patients having major SLE-related organ involvement, at 36 to 40 ng/ml and b) patients with 25-hydroxyvitamin D 2 plus 25-hydroxyvitamin D 3 levels at or above 30 ng/ml should not be treated with vitamin D unless they have major SLE-related organ involvement in which case they should be treated with 25-hydroxyvitamin D 2 plus 25-hydroxyvitamin D 3 to maintain their serum vitamin D levels between 36 and 40 ng/ml. Studies of identical twins (i.e., twins that develop from

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