Complement System Proteins
Complement Membrane Attack Complex
Complement Inactivator Proteins
Complement C3-C5 Convertases
Complement Factor B
Complement Pathway, Alternative
Complement Pathway, Classical
Receptors, Complement 3b
Complement Factor H
Receptor, Anaphylatoxin C5a
Complement Activating Enzymes
Complement Inactivating Agents
Complement Hemolytic Activity Assay
Complement C1 Inactivator Proteins
Receptors, Complement 3d
Complement Fixation Tests
Complement Factor D
Complement Factor I
Complement C4b-Binding Protein
Complement C3b Inactivator Proteins
Complement C3-C5 Convertases, Classical Pathway
Complement C3-C5 Convertases, Alternative Pathway
Complement C1 Inhibitor Protein
Complement C3 Convertase, Alternative Pathway
Complement C5 Convertase, Classical Pathway
Molecular Sequence Data
Complement C3 Convertase, Classical Pathway
Lupus Erythematosus, Systemic
Complement C5 Convertase, Alternative Pathway
Amino Acid Sequence
Complement Pathway, Mannose-Binding Lectin
Complement C5a, des-Arginine
Genetic Complementation Test
Enzyme-Linked Immunosorbent Assay
Major Histocompatibility Complex
Disease Models, Animal
Blood Bactericidal Activity
Electrophoresis, Polyacrylamide Gel
Complement C3 Nephritic Factor
Surface Plasmon Resonance
Sequence Homology, Amino Acid
Polymerase Chain Reaction
Gene Expression Regulation
Mannose-Binding Protein-Associated Serine Proteases
Adrenal Hyperplasia, Congenital
Protein Structure, Tertiary
Sequence Homology, Nucleic Acid
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Reverse Transcriptase Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Immune Adherence Reaction
Fluorescent Antibody Technique
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Immune Complex Diseases
The N-terminal CUB-epidermal growth factor module pair of human complement protease C1r binds Ca2+ with high affinity and mediates Ca2+-dependent interaction with C1s. (1/76)The Ca2+-dependent interaction between complement serine proteases C1r and C1s is mediated by their alpha regions, encompassing the major part of their N-terminal CUB-EGF-CUB (where EGF is epidermal growth factor) module array. In order to define the boundaries of the C1r domain(s) responsible for Ca2+ binding and Ca2+-dependent interaction with C1s and to assess the contribution of individual modules to these functions, the CUB, EGF, and CUB-EGF fragments were expressed in eucaryotic systems or synthesized chemically. Gel filtration studies, as well as measurements of intrinsic Tyr fluorescence, provided evidence that the CUB-EGF pair adopts a more compact conformation in the presence of Ca2+. Ca2+-dependent interaction of intact C1r with C1s was studied using surface plasmon resonance spectroscopy, yielding KD values of 10.9-29.7 nM. The C1r CUB-EGF pair bound immobilized C1s with a higher KD (1.5-1.8 microM), which decreased to 31.4 nM when CUB-EGF was used as the immobilized ligand and C1s was free. Half-maximal binding was obtained at comparable Ca2+ concentrations ranging from 5 microM with intact C1r to 10-16 microM for C1ralpha and CUB-EGF. The isolated CUB and EGF fragments or a CUB + EGF mixture did not bind C1s. These data demonstrate that the C1r CUB-EGF module pair (residues 1-175) is the minimal segment required for high affinity Ca2+ binding and Ca2+-dependent interaction with C1s and indicate that Ca2+ binding induces a more compact folding of the CUB-EGF pair. (+info)
A novel PCR-based technique using expressed sequence tags and gene homology for murine genetic mapping: localization of the complement genes. (2/76)The complement system is a cascade of serum proteins and receptors which forms a vital arm of innate immunity and enhances the adaptive immune response. This work establishes the chromosomal localization of four key genes of the murine complement system. Mapping was performed using a novel and rapid PCR restriction length polymorphism method which was developed to exploit the murine expressed sequence tag (EST) database. This technique circumvents the laborious cDNA or genomic cloning steps of other mapping methods by relying on EST data and the prediction of exon-intron boundaries. This method can be easily applied to the genes of other systems, ranging from the interests of the individual researcher to large-scale gene localization projects. Here the complement system, probably one of the most well-characterized areas of immunology, was used as a model system. It was shown that the C3a receptor C1r and C1s genes form an unexpected complement gene cluster towards the telomeric end of chromosome 6. The second mannose binding lectin-associated serine protease gene was mapped to the telomeric end of chromosome 4, which is distinct from other complement-activating serine proteases. These results provide new insights into the evolution of this group of proteins. (+info)
Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19. (3/76)Mannan-binding lectin (MBL) and C1q activate the complement cascade via attached serine proteases. The proteases C1r and C1s were initially discovered in a complex with C1q, whereas the MBL-associated serine proteases 1 and 2 (MASP-1 and -2) were discovered in a complex with MBL. There is controversy as to whether MBL can utilize C1r and C1s or, inversely, whether C1q can utilize MASP-1 and 2. Serum deficient in C1r produced no complement activation in IgG-coated microwells, whereas activation was seen in mannan-coated microwells. In serum, C1r and C1s were found to be associated only with C1q, whereas MASP-1, MASP-2, and a third protein, MAp19 (19-kDa MBL-associated protein), were found to be associated only with MBL. The bulk of MASP-1 and MAp19 was found in association with each other and was not bound to MBL or MASP-2. The interactions of MASP-1, MASP-2, and MAp19 with MBL differ from those of C1r and C1s with C1q in that both high salt concentrations and calcium chelation (EDTA) are required to fully dissociate the MASPs or MAp19 from MBL. In the presence of calcium, most of the MASP-1, MASP-2, and MAp19 emerged on gel-permeation chromatography as large complexes that were not associated with MBL, whereas in the presence of EDTA most of these components formed smaller complexes. Over 95% of the total MASPs and MAp19 found in serum are not complexed with MBL. (+info)
The cleavage of two C1s subunits by a single active C1r reveals substantial flexibility of the C1s-C1r-C1r-C1s tetramer in the C1 complex. (4/76)The activation of the C1s-C1r-C1r-C1s tetramer in the C1 complex, which involves the cleavage of an Arg-Ile bond in the catalytic domains of the subcomponents, is a two-step process. First, the autolytic activation of C1r takes place, then activated C1r cleaves zymogen C1s. The Arg463Gln mutant of C1r (C1rQI) is stabilized in the zymogen form. This mutant was used to form a C1q-(C1s-C1rQI-C1r-C1s) heteropentamer to study the relative position of the C1r and C1s subunits in the C1 complex. After triggering the C1 by IgG-Sepharose, both C1s subunits are cleaved by the single proteolytically active C1r subunit in the C1s-C1rQI-C1r-C1s tetramer. This finding indicates that the tetramer is flexible enough to adopt different conformations within the C1 complex during the activation process, enabling the single active C1r to cleave both C1s, the neighboring and the sequentially distant one. (+info)
Identification of cDNA encoding a serine protease homologous to human complement C1r precursor from grafted mouse skin. (5/76)We isolated a cDNA clone from grafted mouse skin that encodes a serine protease homologous to human C1r. The C1r protease is involved in the activation of the first component of the classical pathway in the complement system. In order to identify novel transcripts whose expression is regulated in grafted mouse skin, we first performed differential display reverse transcription polymerase chain reaction analysis and obtained 18 partial cDNA clones whose protein products are likely to play an important role in allograft rejection. One of these showed significant sequence homology with human complement C1r precursor. The other clones displayed no homology to any known sequences, however. Northern blot analysis demonstrated that the level of this transcript was upregulated in day 8 postgrafted skin. The full-length cDNA 2121 nucleotides in length obtained from screening a mouse skin cDNA library contained a single open reading frame encoding 707 amino acid residues with a calculated molecular weight of 80,732 Da. Its deduced amino acid sequence revealed an 81% identity and 89% similarity to the human C1r counterpart. In particular, mouse C1r contained His501, Asp559, and Ser656, which were conserved among this group of serine proteases. This protein was thus designated as mouse C1r. We have expressed a truncated fragment of C1r protein without the N-terminal hydrophobic sequence in Escherichia coli and generated a polyclonal antibody against it. Subsequent immunohistochemical analysis confirmed that mouse C1r was significantly expressed 8 d after the skin graft in both allografted and autografted skins, compared with normal skins. These collective data suggest that a component of the complement system, C1r, might contribute to the graft versus host immune responses in mice. (+info)
Assembly and enzymatic properties of the catalytic domain of human complement protease C1r. (6/76)The catalytic properties of C1r, the protease that mediates activation of the C1 complex of complement, are mediated by its C-terminal region, comprising two complement control protein (CCP) modules followed by a serine protease (SP) domain. Baculovirus-mediated expression was used to produce fragments containing the SP domain and either 2 CCP modules (CCP1/2-SP) or only the second CCP module (CCP2-SP). In each case, the wild-type species and two mutants stabilized in the proenzyme form by mutations at the cleavage site (R446Q) or at the active site serine residue (S637A), were produced. Both wild-type fragments were recovered as two-chain, activated proteases, whereas all mutants retained a single-chain, proenzyme structure, providing the first experimental evidence that C1r activation is an autolytic process. As shown by sedimentation velocity analysis, all CCP1/2-SP fragments were dimers (5.5-5.6 S), and all CCP2-SP fragments were monomers (3.2-3.4 S). Thus, CCP1 is essential to the assembly of the dimer, but formation of a stable dimer is not a prerequisite for self-activation. Activation of the R446Q mutants could be achieved by extrinsic cleavage by thermolysin, which cleaved the CCP2-SP species more efficiently than the CCP1/2-SP species and yielded enzymes with C1s-cleaving activities similar to their active wild-type counterparts. C1r and its activated fragments all cleaved C1s, with relative efficiencies in the order C1r < CCP1/2-SP < CCP2-SP, indicating that CCP1 is not involved in C1s recognition. (+info)
C1 inhibitor: analysis of the role of amino acid residues within the reactive center loop in target protease recognition. (7/76)Previous analysis of a naturally occurring C1 inhibitor P2 mutant (Ala(443)-->Val) indicated a role for P2 in specificity determination. To define this role and that of other reactive center loop residues, a number of different amino acids were introduced at P2, as well as at P6 (Ala(439)) and P8'/9' (Gln(452)Gln(453)). Ala(439)-->Val is a naturally occurring mutant observed in a patient with hereditary angioedema. Previous data suggested that Gln(452)Gln(453) might be a contact site for C1s. Reactivity of the inhibitors toward target (C1s, C1r, kallikrein, beta factor XIIa, and plasmin) and nontarget proteases (alpha-thrombin and trypsin) were studied. Substitution of P2 with bulky or charged residues resulted in decreased reactivity with all target proteases. Substitution with residues with hydrophobic or polar side chains resulted in decreased reactivity with some proteases, but in unaltered or increased reactivity with others. Second order rate constants for the reaction with C1s were determined for the mutants with activities most similar to the wild-type protein. The three P2 mutants showed reductions in rate from 3.35 x 10(5) M(-1)s(-1) for the wild type to 1.61, 1.29, and 0.63 x 10(5) for the Ser, Thr, and Val mutants, respectively. In contrast, the Ala(439)-->Val and the Gln(452)Gln(453)-->Ala mutants showed little difference in association rates with C1s, in comparison with the wild-type inhibitor. The data confirm the importance of P2 in specificity determination. However, the P6 position appears to be of little, if any, importance. Furthermore, it appears unlikely that Gln(452)Gln(453) comprise a portion of a protease contact site within the inhibitor. (+info)
The role of the individual domains in the structure and function of the catalytic region of a modular serine protease, C1r. (8/76)The first enzymatic event in the classical pathway of complement activation is autoactivation of the C1r subcomponent of the C1 complex. Activated C1r then cleaves and activates zymogen C1s. C1r is a multidomain serine protease consisting of N-terminal alpha region interacting with other subcomponents and C-terminal gammaB region mediating proteolytic activity. The gammaB region consists of two complement control protein modules (CCP1, CCP2) and a serine protease domain (SP). To clarify the role of the individual domains in the structural and functional properties of the gammaB region we produced the CCP1-CCP2-SP (gammaB), the CCP2-SP, and the SP fragments in recombinant form in Escherichia coli. We successfully renatured the inclusion body proteins. After renaturation all three fragments were obtained in activated form and showed esterolytic activity on synthetic substrates similar to each other. To study the self-activation process in detail zymogen mutant forms of the three fragments were constructed and expressed. Our major statement is that the ability of autoactivation and C1s cleavage is an inherent property of the SP domain. We observed that the CCP2 module significantly increases proteolytic activity of the SP domain on natural substrate, C1s. Therefore, we propose that CCP2 module provides accessory binding sites. Differential scanning calorimetric measurements demonstrated that CCP2 domain greatly stabilizes the structure of SP domain. Deletion of CCP1 domain from the CCP1-CCP2-SP fragment results in the loss of the dimeric structure. Our experiments also provided evidence that dimerization of C1r is not a prerequisite for autoactivation. (+info)
There are two main types of hemolysis:
1. Intravascular hemolysis: This type occurs within the blood vessels and is caused by factors such as mechanical injury, oxidative stress, and certain infections.
2. Extravascular hemolysis: This type occurs outside the blood vessels and is caused by factors such as bone marrow disorders, splenic rupture, and certain medications.
Hemolytic anemia is a condition that occurs when there is excessive hemolysis of RBCs, leading to a decrease in the number of healthy red blood cells in the body. This can cause symptoms such as fatigue, weakness, pale skin, and shortness of breath.
Some common causes of hemolysis include:
1. Genetic disorders such as sickle cell anemia and thalassemia.
2. Autoimmune disorders such as autoimmune hemolytic anemia (AIHA).
3. Infections such as malaria, babesiosis, and toxoplasmosis.
4. Medications such as antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and blood thinners.
5. Bone marrow disorders such as aplastic anemia and myelofibrosis.
6. Splenic rupture or surgical removal of the spleen.
7. Mechanical injury to the blood vessels.
Diagnosis of hemolysis is based on a combination of physical examination, medical history, and laboratory tests such as complete blood count (CBC), blood smear examination, and direct Coombs test. Treatment depends on the underlying cause and may include supportive care, blood transfusions, and medications to suppress the immune system or prevent infection.
The term "systemic" refers to the fact that the disease affects multiple organ systems, including the skin, joints, kidneys, lungs, and nervous system. LES is a complex condition, and its symptoms can vary widely depending on which organs are affected. Common symptoms include fatigue, fever, joint pain, rashes, and swelling in the extremities.
There are several subtypes of LES, including:
1. Systemic lupus erythematosus (SLE): This is the most common form of the disease, and it can affect anyone, regardless of age or gender.
2. Discoid lupus erythematosus (DLE): This subtype typically affects the skin, causing a red, scaly rash that does not go away.
3. Drug-induced lupus erythematosus: This form of the disease is caused by certain medications, and it usually resolves once the medication is stopped.
4. Neonatal lupus erythematosus: This rare condition affects newborn babies of mothers with SLE, and it can cause liver and heart problems.
There is no cure for LES, but treatment options are available to manage the symptoms and prevent flares. Treatment may include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, immunosuppressive medications, and antimalarial drugs. In severe cases, hospitalization may be necessary to monitor and treat the disease.
It is important for people with LES to work closely with their healthcare providers to manage their condition and prevent complications. With proper treatment and self-care, many people with LES can lead active and fulfilling lives.
Idiopathic membranous nephropathy (IMN) is an autoimmune disorder that causes GNM without any identifiable cause. Secondary membranous nephropathy, on the other hand, is caused by systemic diseases such as lupus or cancer.
The symptoms of GNM can vary depending on the severity of the disease and may include blood in the urine, proteinuria, edema, high blood pressure, and decreased kidney function. The diagnosis of GNM is based on a combination of clinical findings, laboratory tests, and renal biopsy.
Treatment for GNM is aimed at slowing the progression of the disease and managing symptoms. Medications such as corticosteroids, immunosuppressive drugs, and blood pressure-lowering drugs may be used to treat GNM. In some cases, kidney transplantation may be necessary.
The prognosis for GNM varies depending on the severity of the disease and the underlying cause. In general, the prognosis for IMN is better than for secondary membranous nephropathy. With proper treatment, some patients with GNM can experience a slowing or stabilization of the disease, while others may progress to end-stage renal disease (ESRD).
The cause of GNM is not fully understood, but it is believed to be an autoimmune disorder that leads to inflammation and damage to the glomerular membrane. Genetic factors and environmental triggers may also play a role in the development of GNM.
There are several risk factors for developing GNM, including family history, age (GMN is more common in adults), and certain medical conditions such as hypertension and diabetes.
The main complications of GNM include:
1. ESRD: Progression to ESRD is a common outcome of untreated GNM.
2. High blood pressure: GNM can lead to high blood pressure, which can further damage the kidneys.
3. Infections: GNM increases the risk of infections due to impaired immune function.
4. Kidney failure: GNM can cause chronic kidney failure, leading to the need for dialysis or a kidney transplant.
5. Cardiovascular disease: GNM is associated with an increased risk of cardiovascular disease, including heart attack and stroke.
6. Malnutrition: GNM can lead to malnutrition due to decreased appetite, nausea, and vomiting.
7. Bone disease: GNM can cause bone disease, including osteoporosis and bone pain.
8. Anemia: GNM can cause anemia, which can lead to fatigue, weakness, and shortness of breath.
9. Increased risk of infections: GNM increases the risk of infections due to impaired immune function.
10. Decreased quality of life: GNM can significantly decrease a person's quality of life, leading to decreased mobility, pain, and discomfort.
It is important for individuals with GNM to receive early diagnosis and appropriate treatment to prevent or delay the progression of these complications.
The symptoms of glomerulonephritis can vary depending on the underlying cause of the disease, but may include:
* Blood in the urine (hematuria)
* Proteinuria (excess protein in the urine)
* Reduced kidney function
* Swelling in the legs and ankles (edema)
* High blood pressure
Glomerulonephritis can be caused by a variety of factors, including:
* Infections such as staphylococcal or streptococcal infections
* Autoimmune disorders such as lupus or rheumatoid arthritis
* Allergic reactions to certain medications
* Genetic defects
* Certain diseases such as diabetes, high blood pressure, and sickle cell anemia
The diagnosis of glomerulonephritis typically involves a physical examination, medical history, and laboratory tests such as urinalysis, blood tests, and kidney biopsy.
Treatment for glomerulonephritis depends on the underlying cause of the disease and may include:
* Antibiotics to treat infections
* Medications to reduce inflammation and swelling
* Diuretics to reduce fluid buildup in the body
* Immunosuppressive medications to suppress the immune system in cases of autoimmune disorders
* Dialysis in severe cases
The prognosis for glomerulonephritis depends on the underlying cause of the disease and the severity of the inflammation. In some cases, the disease may progress to end-stage renal disease, which requires dialysis or a kidney transplant. With proper treatment, however, many people with glomerulonephritis can experience a good outcome and maintain their kidney function over time.
Arteriolosclerosis is often associated with conditions such as hypertension, diabetes, and atherosclerosis, which is the buildup of plaque in the arteries. It can also be caused by other factors such as smoking, high cholesterol levels, and inflammation.
The symptoms of arteriolosclerosis can vary depending on the location and severity of the condition, but may include:
* Decreased blood flow to organs or tissues
* Shortness of breath
* Dizziness or lightheadedness
* Pain in the affected limbs or organs
Arteriolosclerosis is typically diagnosed through a combination of physical examination, medical history, and diagnostic tests such as ultrasound, angiography, or blood tests. Treatment for the condition may include lifestyle changes such as exercise and dietary modifications, medications to control risk factors such as hypertension and high cholesterol, and in some cases, surgical intervention to open or bypass blocked arterioles.
In summary, arteriolosclerosis is a condition where the arterioles become narrowed or obstructed, leading to decreased blood flow to organs and tissues and potentially causing a range of health problems. It is often associated with other conditions such as hypertension and atherosclerosis, and can be diagnosed through a combination of physical examination, medical history, and diagnostic tests. Treatment may include lifestyle changes and medications to control risk factors, as well as surgical intervention in some cases.
1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.
2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.
3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.
4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.
5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.
6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.
7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.
8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.
9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.
10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.
There are several types of lupus nephritis, each with its own unique characteristics and symptoms. The most common forms include:
* Class I (mesangial proliferative glomerulonephritis): This type is characterized by the growth of abnormal cells in the glomeruli (blood-filtering units of the kidneys).
* Class II (active lupus nephritis): This type is characterized by widespread inflammation and damage to the kidneys, with or without the presence of antibodies.
* Class III (focal lupus nephritis): This type is characterized by localized inflammation in certain areas of the kidneys.
* Class IV (lupus nephritis with crescentic glomerulonephritis): This type is characterized by widespread inflammation and damage to the kidneys, with crescent-shaped tissue growth in the glomeruli.
* Class V (lupus nephritis with sclerotic changes): This type is characterized by hardening and shrinkage of the glomeruli due to scarring.
Lupus Nephritis can cause a range of symptoms, including:
* Proteinuria (excess protein in the urine)
* Hematuria (blood in the urine)
* Reduced kidney function
* Swelling (edema)
* Joint pain
Lupus Nephritis can be diagnosed through a combination of physical examination, medical history, laboratory tests, and kidney biopsy. Treatment options for lupus nephritis include medications to suppress the immune system, control inflammation, and prevent further damage to the kidneys. In severe cases, dialysis or a kidney transplant may be necessary.
There are several key features of inflammation:
1. Increased blood flow: Blood vessels in the affected area dilate, allowing more blood to flow into the tissue and bringing with it immune cells, nutrients, and other signaling molecules.
2. Leukocyte migration: White blood cells, such as neutrophils and monocytes, migrate towards the site of inflammation in response to chemical signals.
3. Release of mediators: Inflammatory mediators, such as cytokines and chemokines, are released by immune cells and other cells in the affected tissue. These molecules help to coordinate the immune response and attract more immune cells to the site of inflammation.
4. Activation of immune cells: Immune cells, such as macrophages and T cells, become activated and start to phagocytose (engulf) pathogens or damaged tissue.
5. Increased heat production: Inflammation can cause an increase in metabolic activity in the affected tissue, leading to increased heat production.
6. Redness and swelling: Increased blood flow and leakiness of blood vessels can cause redness and swelling in the affected area.
7. Pain: Inflammation can cause pain through the activation of nociceptors (pain-sensing neurons) and the release of pro-inflammatory mediators.
Inflammation can be acute or chronic. Acute inflammation is a short-term response to injury or infection, which helps to resolve the issue quickly. Chronic inflammation is a long-term response that can cause ongoing damage and diseases such as arthritis, asthma, and cancer.
There are several types of inflammation, including:
1. Acute inflammation: A short-term response to injury or infection.
2. Chronic inflammation: A long-term response that can cause ongoing damage and diseases.
3. Autoimmune inflammation: An inappropriate immune response against the body's own tissues.
4. Allergic inflammation: An immune response to a harmless substance, such as pollen or dust mites.
5. Parasitic inflammation: An immune response to parasites, such as worms or fungi.
6. Bacterial inflammation: An immune response to bacteria.
7. Viral inflammation: An immune response to viruses.
8. Fungal inflammation: An immune response to fungi.
There are several ways to reduce inflammation, including:
1. Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying anti-rheumatic drugs (DMARDs).
2. Lifestyle changes, such as a healthy diet, regular exercise, stress management, and getting enough sleep.
3. Alternative therapies, such as acupuncture, herbal supplements, and mind-body practices.
4. Addressing underlying conditions, such as hormonal imbalances, gut health issues, and chronic infections.
5. Using anti-inflammatory compounds found in certain foods, such as omega-3 fatty acids, turmeric, and ginger.
It's important to note that chronic inflammation can lead to a range of health problems, including:
3. Heart disease
5. Alzheimer's disease
6. Parkinson's disease
7. Autoimmune disorders, such as lupus and rheumatoid arthritis.
Therefore, it's important to manage inflammation effectively to prevent these complications and improve overall health and well-being.
There are three main forms of ACH:
1. Classic congenital adrenal hyperplasia (CAH): This is the most common form of ACH, accounting for about 90% of cases. It is caused by mutations in the CYP21 gene, which codes for an enzyme that converts cholesterol into cortisol and aldosterone.
2. Non-classic CAH (NCAH): This form of ACH is less common than classic CAH and is caused by mutations in other genes involved in cortisol and aldosterone production.
3. Mineralocorticoid excess (MOE) or glucocorticoid deficiency (GD): These are rare forms of ACH that are characterized by excessive production of mineralocorticoids (such as aldosterone) or a deficiency of glucocorticoids (such as cortisol).
The symptoms of ACH can vary depending on the specific form of the disorder and the age at which it is diagnosed. In classic CAH, symptoms typically appear in infancy and may include:
* Premature puberty (in girls) or delayed puberty (in boys)
* Abnormal growth patterns
* Distended abdomen
* Weight gain or obesity
* Easy bruising or bleeding
In NCAH and MOE/GD, symptoms may be less severe or may not appear until later in childhood or adulthood. They may include:
* High blood pressure
* Low blood sugar (hypoglycemia)
* Weight gain or obesity
* Mood changes
If left untreated, ACH can lead to serious complications, including:
* Adrenal gland insufficiency
* Heart problems
* Bone health problems
* Increased risk of infections
* Mental health issues (such as depression or anxiety)
Treatment for ACH typically involves hormone replacement therapy to restore the balance of hormones in the body. This may involve taking medications such as cortisol, aldosterone, or other hormones to replace those that are deficient or imbalanced. In some cases, surgery may be necessary to remove an adrenal tumor or to correct physical abnormalities.
With proper treatment, many individuals with ACH can lead healthy, active lives. However, it is important for individuals with ACH to work closely with their healthcare providers to manage their condition and prevent complications. This may involve regular check-ups, hormone level monitoring, and lifestyle changes such as a healthy diet and regular exercise.
Proteinuria is usually diagnosed by a urine protein-to-creatinine ratio (P/C ratio) or a 24-hour urine protein collection. The amount and duration of proteinuria can help distinguish between different underlying causes and predict prognosis.
Proteinuria can have significant clinical implications, as it is associated with increased risk of cardiovascular disease, kidney damage, and malnutrition. Treatment of the underlying cause can help reduce or eliminate proteinuria.
There are two main types of MD:
1. Dry Macular Degeneration (DMD): This is the most common form of MD, accounting for about 90% of cases. It is caused by the gradual accumulation of waste material in the macula, which can lead to cell death and vision loss over time.
2. Wet Macular Degeneration (WMD): This type of MD is less common but more aggressive, accounting for about 10% of cases. It occurs when new blood vessels grow underneath the retina, leaking fluid and causing damage to the macula. This can lead to rapid vision loss if left untreated.
The symptoms of MD can vary depending on the severity and type of the condition. Common symptoms include:
* Blurred vision
* Distorted vision (e.g., straight lines appearing wavy)
* Difficulty reading or recognizing faces
* Difficulty adjusting to bright light
* Blind spots in central vision
MD can have a significant impact on daily life, making it difficult to perform everyday tasks such as driving, reading, and recognizing faces.
There is currently no cure for MD, but there are several treatment options available to slow down the progression of the disease and manage its symptoms. These include:
* Anti-vascular endothelial growth factor (VEGF) injections: These medications can help prevent the growth of new blood vessels and reduce inflammation in the macula.
* Photodynamic therapy: This involves the use of a light-sensitive drug and low-intensity laser to damage and shrink the abnormal blood vessels in the macula.
* Vitamin supplements: Certain vitamins, such as vitamin C, E, and beta-carotene, have been shown to slow down the progression of MD.
* Laser surgery: This can be used to reduce the number of abnormal blood vessels in the macula and improve vision.
It is important for individuals with MD to receive regular monitoring and treatment from an eye care professional to manage their condition and prevent complications.
There are several types of disease susceptibility, including:
1. Genetic predisposition: This refers to the inherent tendency of an individual to develop a particular disease due to their genetic makeup. For example, some families may have a higher risk of developing certain diseases such as cancer or heart disease due to inherited genetic mutations.
2. Environmental susceptibility: This refers to the increased risk of developing a disease due to exposure to environmental factors such as pollutants, toxins, or infectious agents. For example, someone who lives in an area with high levels of air pollution may be more susceptible to developing respiratory problems.
3. Lifestyle susceptibility: This refers to the increased risk of developing a disease due to unhealthy lifestyle choices such as smoking, lack of exercise, or poor diet. For example, someone who smokes and is overweight may be more susceptible to developing heart disease or lung cancer.
4. Immune system susceptibility: This refers to the increased risk of developing a disease due to an impaired immune system. For example, people with autoimmune disorders such as HIV/AIDS or rheumatoid arthritis may be more susceptible to opportunistic infections.
Understanding disease susceptibility can help healthcare providers identify individuals who are at risk of developing certain diseases and provide preventive measures or early intervention to reduce the risk of disease progression. Additionally, genetic testing can help identify individuals with a high risk of developing certain diseases, allowing for earlier diagnosis and treatment.
In summary, disease susceptibility refers to the predisposition of an individual to develop a particular disease or condition due to various factors such as genetics, environment, lifestyle choices, and immune system function. Understanding disease susceptibility can help healthcare providers identify individuals at risk and provide appropriate preventive measures or early intervention to reduce the risk of disease progression.
There are several symptoms of RA, including:
1. Joint pain and stiffness, especially in the hands and feet
2. Swollen and warm joints
3. Redness and tenderness in the affected areas
4. Fatigue, fever, and loss of appetite
5. Loss of range of motion in the affected joints
6. Firm bumps of tissue under the skin (rheumatoid nodules)
RA can be diagnosed through a combination of physical examination, medical history, blood tests, and imaging studies such as X-rays or ultrasound. Treatment typically involves a combination of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and biologic agents. Lifestyle modifications such as exercise and physical therapy can also be helpful in managing symptoms and improving quality of life.
There is no cure for RA, but early diagnosis and aggressive treatment can help to slow the progression of the disease and reduce symptoms. With proper management, many people with RA are able to lead active and fulfilling lives.
Explanation: Genetic predisposition to disease is influenced by multiple factors, including the presence of inherited genetic mutations or variations, environmental factors, and lifestyle choices. The likelihood of developing a particular disease can be increased by inherited genetic mutations that affect the functioning of specific genes or biological pathways. For example, inherited mutations in the BRCA1 and BRCA2 genes increase the risk of developing breast and ovarian cancer.
The expression of genetic predisposition to disease can vary widely, and not all individuals with a genetic predisposition will develop the disease. Additionally, many factors can influence the likelihood of developing a particular disease, such as environmental exposures, lifestyle choices, and other health conditions.
Inheritance patterns: Genetic predisposition to disease can be inherited in an autosomal dominant, autosomal recessive, or multifactorial pattern, depending on the specific disease and the genetic mutations involved. Autosomal dominant inheritance means that a single copy of the mutated gene is enough to cause the disease, while autosomal recessive inheritance requires two copies of the mutated gene. Multifactorial inheritance involves multiple genes and environmental factors contributing to the development of the disease.
Examples of diseases with a known genetic predisposition:
1. Huntington's disease: An autosomal dominant disorder caused by an expansion of a CAG repeat in the Huntingtin gene, leading to progressive neurodegeneration and cognitive decline.
2. Cystic fibrosis: An autosomal recessive disorder caused by mutations in the CFTR gene, leading to respiratory and digestive problems.
3. BRCA1/2-related breast and ovarian cancer: An inherited increased risk of developing breast and ovarian cancer due to mutations in the BRCA1 or BRCA2 genes.
4. Sickle cell anemia: An autosomal recessive disorder caused by a point mutation in the HBB gene, leading to defective hemoglobin production and red blood cell sickling.
5. Type 1 diabetes: An autoimmune disease caused by a combination of genetic and environmental factors, including multiple genes in the HLA complex.
Understanding the genetic basis of disease can help with early detection, prevention, and treatment. For example, genetic testing can identify individuals who are at risk for certain diseases, allowing for earlier intervention and preventive measures. Additionally, understanding the genetic basis of a disease can inform the development of targeted therapies and personalized medicine."
The disorder is caused by mutations in the HBB gene that codes for the beta-globin subunit of hemoglobin. These mutations result in the production of abnormal hemoglobins that are unstable and prone to breakdown, leading to the release of free hemoglobin into the urine.
HP is classified into two types based on the severity of symptoms:
1. Type 1 HP: This is the most common form of the disorder and is characterized by mild to moderate anemia, occasional hemoglobinuria, and a normal life expectancy.
2. Type 2 HP: This is a more severe form of the disorder and is characterized by severe anemia, recurrent hemoglobinuria, and a shorter life expectancy.
There is no cure for HP, but treatment options are available to manage symptoms and prevent complications. These may include blood transfusions, folic acid supplements, and medications to reduce the frequency and severity of hemoglobinuria episodes.
The term "immune complex disease" was first used in the 1960s to describe a group of conditions that were thought to be caused by the formation of immune complexes. These diseases include:
1. Systemic lupus erythematosus (SLE): an autoimmune disorder that can affect multiple organ systems and is characterized by the presence of anti-nuclear antibodies.
2. Rheumatoid arthritis (RA): an autoimmune disease that causes inflammation in the joints and can lead to joint damage.
3. Type III hypersensitivity reaction: a condition in which immune complexes are deposited in tissues, leading to inflammation and tissue damage.
4. Pemphigus: a group of autoimmune diseases that affect the skin and mucous membranes, characterized by the presence of autoantibodies against desmosomal antigens.
5. Bullous pemphigoid: an autoimmune disease that affects the skin and is characterized by the formation of large blisters.
6. Myasthenia gravis: an autoimmune disorder that affects the nervous system, causing muscle weakness and fatigue.
7. Goodpasture's syndrome: a rare autoimmune disease that affects the kidneys and lungs, characterized by the presence of immune complexes in the glomeruli of the kidneys.
8. Hemolytic uremic syndrome (HUS): a condition in which red blood cells are destroyed and waste products accumulate in the kidneys, leading to kidney failure.
Immune complex diseases can be caused by various factors, including genetic predisposition, environmental triggers, and exposure to certain drugs or toxins. Treatment options for these diseases include medications that suppress the immune system, such as corticosteroids and immunosuppressive drugs, and plasmapheresis, which is a process that removes harmful antibodies from the blood. In some cases, organ transplantation may be necessary.
In conclusion, immune complex diseases are a group of disorders that occur when the body's immune system mistakenly attacks its own tissues and organs, leading to inflammation and damage. These diseases can affect various parts of the body, including the skin, kidneys, lungs, and nervous system. Treatment options vary depending on the specific disease and its severity, but may include medications that suppress the immune system and plasmapheresis.
Complement component 1s
Complement component 1r
List of MeSH codes (D08)
List of EC numbers (EC 3)
Outline of immunology
Complement component 1q
List of MeSH codes (D12.776.124)
List of primary immunodeficiencies
Classical complement pathway
Idempotent (ring theory)
C1R Mutations Trigger Constitutive Complement 1 Activation in Periodontal Ehlers-Danlos Syndrome - PubMed
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RCSB PDB - 6F1H: C1rC1s complex
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SMART: CCP domain annotation
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Pharos : Ligand List
NCIt Code NCIt PT NICHD Rheumatology PT NICHD Rheumatology SY NCIt Definition NICHD Rheumatology Definition NCIt Code of NICHD...
LI PBMC MENACTRA AGE 18 45YO ANTI DT ANTIBODY CORRELATION PROFILE 3DY DN
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SPR - Integrated Structural Biology, Grenoble
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- In 17 of these families , we identified heterozygous missense or in-frame insertion/ deletion mutations in C1R (15 families ) or C1S (2 families ), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway . (bvsalud.org)
- Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis . (bvsalud.org)
- A Classical Complement Pathway, Mouse, Assay ELISA Kit is a type of ELISA kit that can measure the activity of the classical complement pathway in mouse serum or plasma samples. (immunoconceptindia.co)
- C1q together with C1r and C1s form the first part of the classical complement pathway, C1 macromolecules. (creative-biolabs.com)
- In addition, C1q can also recognize molecular patterns associated with pathogens, and can bind to apoptotic vesicles, thereby activating the classical complement pathway and mediating phagocytosis. (creative-biolabs.com)
- C1q composes together with C1r and C1s the C1 macromolecule, the first component of the classical complement pathway. (hycultbiotech.com)
- Furthermore C1q can bind to apoptotic blebs, where it activates the classical complement pathway and mediates phagocytosis. (hycultbiotech.com)
- The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. (embl.de)
- These modules have been identified more than 140 times in over 20 proteins, including 12 proteins of the complement system. (embl.de)
- Special Complements Research Reagents are products that are used for the analysis of the complement system, a part of the immune system that consists of a series of proteins that can be activated by various stimuli. (immunoconceptindia.co)
- These kits allow for the analysis of activation of key proteins and specific pathways of the complement system in serum, plasma, and other biological fluids. (immunoconceptindia.co)
- Analysis of Protein Array containing more than 19,000 full-length human proteins using Complement C3d-Monospecific Mouse Monoclonal Antibody (C3D/2891). (neobiotechnologies.com)
- The complement component proteins, C2, C3, C4 and C5, are potent anaphylatoxins that are released during complement activation. (neobiotechnologies.com)
- Binding of these proteins to their respective G protein-coupled receptors, C3aR, C1R and C5aR, induces proinflammatory events, such as cellular degranulation, smooth muscle contraction, arachidonic acid metabolism, cytokine release, leukocyte activation and cellular chemotaxis. (neobiotechnologies.com)
- A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. (nih.gov)
- When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. (nih.gov)
- The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. (nih.gov)
- From NCBI Gene: This gene encodes a serine protease, which is a major constituent of the human complement subcomponent C1. (nih.gov)
- Each generates a C3 convertase, a serine protease that cleaves the central complement protein C3, and generates the major cleavage fragment C3b. (eaglebio.com)
Subcomponent of complement1
- Mouse anti Human C1s antibody, clone M81, recognizes human C1s, a subcomponent of complement component 1 (C1). (bio-rad-antibodies.com)
- No fragment is released when either C1r or C1s is cleaved. (nih.gov)
- The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes. (antibodies-online.com)
- SDS-PAGE Analysis Purified Complement 3d Mouse Monoclonal Antibody (C3D/2891). (neobiotechnologies.com)
- Formalin-fixed, paraffin-embedded human rejected kidney transplant stained with Complement 3d Mouse Monoclonal Antibody (C3D/2891) at 2ug/ml in PBS. (neobiotechnologies.com)
- C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. (antibodies-online.com)
- A polymorphism in the complement component C1r is not associated with sporadic Alzheimer's disease. (cdc.gov)
- After liquid chromatography-tandem mass spectrometry analysis, the relative plasma levels of alpha-2-macroglobulin (A2M), C4b-binding protein alpha chain (C4BPA), complement C1r subcomponent-like protein (C1RL), complement component C6 (C6), complement component C8 gamma chain (C8G), and vitamin K-dependent protein S (PROS) were significantly different between the CRPS and CR groups. (tmu.edu.tw)
- C1 is a large inactive plasma complex containing one subunit of C1q, 2 subunits of C1r and 2 C1s subunits, which are non-covalently bound together. (bio-rad-antibodies.com)
Innate and adaptive1
- The complement system plays important roles in both innate and adaptive immune response and can produce an inflammatory and protective reaction to challenges from pathogens before an adaptive response can occur. (eaglebio.com)
- An Alternative Complement Pathway, Rat, Assay ELISA Kit is a type of assay kit that can measure the activity of the alternative complement pathway in rat serum or plasma samples. (immunoconceptindia.co)
- The solution structure of the 16th CCP module from human complement factor H has been determined by a combination of 2-dimensional nuclear magnetic resonance spectroscopy and restrained simulated annealing. (embl.de)
- complement factor H [Source:HGNC Symbol;Acc:H. (gsea-msigdb.org)
- This gene encodes a member of the signal peptide, complement subcomponents C1r/C1s, Uegf, bone morphogenetic protein-1 and epidermal growth factor-like domain containing protein family. (nih.gov)
- C3d is a terminal degradation product of C3 that plays an important role in modulation of the adaptive immune response through the interaction with complement receptor type 2 (CR2). (neobiotechnologies.com)
- Transcriptome Analysis of Post-Mortem Brain Tissue Reveals Up-Regulation of the Complement Cascade in a Subgroup of Schizophrenia Patients. (scilifelab.se)
- As a result the activation of the complement system is blocked. (eaglebio.com)
- This binding by C1q results in the auto-activation of C1r which subsequently releases active C1s units. (bio-rad-antibodies.com)
- We identified a novel, homozygous, loss-of-function mutation (p.Pro445Leufs*11) in the C1R gene. (nih.gov)
- C1-INH binding of C1 to the catalytic site of both C1r and C1s releases the latter two from the complex. (eaglebio.com)
- The increased complement expression is primarily driven by a subgroup of patients with increased expression of immune/inflammatory response genes, pointing to important differences in disease etiology within the patient group. (scilifelab.se)
- complement C1q C chain [Source:HGNC Symbol;Ac. (gsea-msigdb.org)
- When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. (nih.gov)
- Deficiencies in C1-INH allow unchecked activation of the classic complement pathway and other biochemical systems including the bradykinin system. (medscape.com)
- The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. (nih.gov)
- The complement components C3c and C4 as well as the immunoglobulins G (IgG), A (IgA) and M (IgM) were measured by nephelometry (Behring Nephelometer II Analyzer, Germany). (medscape.com)
- 8. Tumour-cell-derived complement components C1r and C1s promote growth of cutaneous squamous cell carcinoma. (nih.gov)