Palaeoimmunology

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ELISA: a common immunoassay ELISA.jpg
ELISA: a common immunoassay

Palaeoimmunology or paleo-immunology ("paleo"=ancient, "immuno"=referring to immunology) is the analysis using histochemical techniques to look at the matrix proteins in historic and pre-historic materials. [1] Modern immunological assays are used to detect the presence of specific antigens in the sample material. Specimens subject to immunoassays have usually been preserved in a way that has prevented biomolecular targets from degrading. This has either been achieved through natural preservative circumstances, such as accelerated fossilization, [2] or through artificial mummification. [1] [3] [4] Regardless of the path taken to achieve this state, preservation has occurred before the denaturing of antigenic targets. The purpose of applying immunological assays to archaeological materials is to better understand the biochemical makeup and composition of these pre-historic samples. [1] [2] [5] Antigenic elements within these materials may reveal information regarding the "life" and "death" of the sample being studied. [1] [3] [4] [6]

Examples of use

Paleo-immunology encompasses a variety of immunoassays performed on a diverse array of archaeological materials. Paleo-immunology is a new, growing field that is still being properly defined. Examples of paleo-immunology as they appear in peer reviewed literature are as follows:

Related Research Articles

Antigen Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. The term antigen originally referred to a substance that is an antibody generator. Antigens can be proteins, peptides, polysaccharides, lipids, or nucleic acids.

Antibody Protein(s) forming a major part of an organisms immune system

An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

ELISA Method to detect an antigen using an antibody and enzyme

The enzyme-linked immunosorbent assay (ELISA) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence of a ligand in a liquid sample using antibodies directed against the protein to be measured. ELISA has been used as a diagnostic tool in medicine, plant pathology, and biotechnology, as well as a quality control check in various industries.

Microarray A small-scale two-dimensional array of samples on a solid support

A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample. It is a two-dimensional array on a solid substrate—usually a glass slide or silicon thin-film cell—that assays (tests) large amounts of biological material using high-throughput screening miniaturized, multiplexed and parallel processing and detection methods. The concept and methodology of microarrays was first introduced and illustrated in antibody microarrays by Tse Wen Chang in 1983 in a scientific publication and a series of patents. The "gene chip" industry started to grow significantly after the 1995 Science Magazine article by the Ron Davis and Pat Brown labs at Stanford University. With the establishment of companies, such as Affymetrix, Agilent, Applied Microarrays, Arrayjet, Illumina, and others, the technology of DNA microarrays has become the most sophisticated and the most widely used, while the use of protein, peptide and carbohydrate microarrays is expanding.

<i>Plasmodium falciparum</i> Protozoan species of malaria parasite

Plasmodium falciparum is a unicellular protozoan parasite of humans, and the deadliest species of Plasmodium that causes malaria in humans. The parasite is transmitted through the bite of a female Anopheles mosquito and causes the disease's most dangerous form, falciparum malaria. It is responsible for around 50% of all malaria cases. P. falciparum is therefore regarded as the deadliest parasite in humans. It is also associated with the development of blood cancer and is classified as a Group 2A (probable) carcinogen.

Immunoassay Biochemical test for a protein or other molecule using an antibody

An immunoassay (IA) is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody (usually) or an antigen (sometimes). The molecule detected by the immunoassay is often referred to as an "analyte" and is in many cases a protein, although it may be other kinds of molecules, of different sizes and types, as long as the proper antibodies that have the required properties for the assay are developed. Analytes in biological liquids such as serum or urine are frequently measured using immunoassays for medical and research purposes.

Merozoite surface protein

Merozoitesurface proteins are both integral and peripheral membrane proteins found on the surface of a merozoite, an early life cycle stage of a protozoan. Merozoite surface proteins, or MSPs, are important in understanding malaria, a disease caused by protozoans of the genus Plasmodium. During the asexual blood stage of its life cycle, the malaria parasite enters red blood cells to replicate itself, causing the classic symptoms of malaria. These surface protein complexes are involved in many interactions of the parasite with red blood cells and are therefore an important topic of study for scientists aiming to combat malaria.

Southeast Asian ovalocytosis is a blood disorder that is similar to, but distinct from hereditary elliptocytosis. It is common in some communities in Malaysia and Papua New Guinea, as it confers some resistance to cerebral Falciparum Malaria.

Digoxigenin Chemical compound

Digoxigenin (DIG) is a steroid found exclusively in the flowers and leaves of the plants Digitalis purpurea, Digitalis orientalis and Digitalis lanata (foxgloves), where it is attached to sugars, to form the glycosides.

Cross-reactivity, in a general sense, is the reactivity of an observed agent which initiates reactions outside the main reaction expected. This has implications for any kind of test or assay, including diagnostic tests in medicine, and can be a cause of false positives. In immunology, the definition of cross-reactivity refers specifically to the reaction of the immune system to antigens. There can be cross-reactivity between the immune system and the antigens of two different pathogens, or between one pathogen and proteins on non-pathogens, which in some cases can be the cause of allergies.

Antibody microarray

An antibody microarray is a specific form of protein microarray. In this technology, a collection of captured antibodies are spotted and fixed on a solid surface such as glass, plastic, membrane, or silicon chip, and the interaction between the antibody and its target antigen is detected. Antibody microarrays are often used for detecting protein expression from various biofluids including serum, plasma and cell or tissue lysates. Antibody arrays may be used for both basic research and medical and diagnostic applications.

Antigenic variation or antigenic alteration refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters the proteins or carbohydrates on its surface and thus avoids a host immune response, making it one of the mechanisms of antigenic escape. It is related to phase variation. Antigenic variation not only enables the pathogen to avoid the immune response in its current host, but also allows re-infection of previously infected hosts. Immunity to re-infection is based on recognition of the antigens carried by the pathogen, which are "remembered" by the acquired immune response. If the pathogen's dominant antigen can be altered, the pathogen can then evade the host's acquired immune system. Antigenic variation can occur by altering a variety of surface molecules including proteins and carbohydrates. Antigenic variation can result from gene conversion, site-specific DNA inversions, hypermutation, or recombination of sequence cassettes. The result is that even a clonal population of pathogens expresses a heterogeneous phenotype. Many of the proteins known to show antigenic or phase variation are related to virulence.

Malaria antigen detection tests

Malaria antigen detection tests are a group of commercially available rapid diagnostic tests of the rapid antigen test type that allow quick diagnosis of malaria by people who are not otherwise skilled in traditional laboratory techniques for diagnosing malaria or in situations where such equipment is not available. There are currently over 20 such tests commercially available. The first malaria antigen suitable as target for such a test was a soluble glycolytic enzyme Glutamate dehydrogenase. None of the rapid tests are currently as sensitive as a thick blood film, nor as cheap. A major drawback in the use of all current dipstick methods is that the result is essentially qualitative. In many endemic areas of tropical Africa, however, the quantitative assessment of parasitaemia is important, as a large percentage of the population will test positive in any qualitative assay.

Basigin Mammalian protein found in Homo sapiens

Basigin (BSG) also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147) is a protein that in humans is encoded by the BSG gene. This protein is a determinant for the Ok blood group system. There are three known antigens in the Ok system; the most common being Oka, OK2 and OK3. Basigin has been shown to be an essential receptor on red blood cells for the human malaria parasite, Plasmodium falciparum.

Malaria vaccine Vaccine that is used to prevent malaria

A malaria vaccine is a vaccine that is used to prevent malaria. The only approved vaccine, as of 2021, is RTS,S, known by the brand name Mosquirix. In October 2021, the WHO for the first time recommended the large-scale use of a malaria vaccine for children living in areas with moderate-to-high malaria transmission. Four injections are required for full protection.

The mainstay of malaria diagnosis has been the microscopic examination of blood, utilizing blood films. Although blood is the sample most frequently used to make a diagnosis, both saliva and urine have been investigated as alternative, less invasive specimens. More recently, modern techniques utilizing antigen tests or polymerase chain reaction have been discovered, though these are not widely implemented in malaria endemic regions. Areas that cannot afford laboratory diagnostic tests often use only a history of subjective fever as the indication to treat for malaria.

Mass spectrometric immunoassay (MSIA) is a rapid method is used to detect and/ or quantify antigens and or antibody analytes. This method uses an analyte affinity isolation to extract targeted molecules and internal standards from biological fluid in preparation for matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). This method allows for "top down" and "bottom up" analysis. This sensitive method allows for a new and improved process for detecting multiple antigens and antibodies in a single assay. This assay is also capable of distinguishing mass shifted forms of the same molecule via a panantibody, as well as distinguish point mutations in proteins. Each specific form is detected uniquely based on their characteristic molecular mass. MSIA has dual specificity because of the antibody-antigen reaction coupled with the power of a mass spectrometer.

Circumsporozoite protein (CSP) is a secreted protein of the sporozoite stage of the malaria parasite and is the antigenic target of RTS,S, a pre-erythrocytic malaria vaccine currently undergoing clinical trials. The amino-acid sequence of CSP consists of an immunodominant central repeat region flanked by conserved motifs at the N- and C- termini that are implicated in protein processing as the parasite travels from the mosquito to the mammalian vector. CSP was discovered by Dame et al 1984 in P. gallinaceum.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a family of proteins present on the membrane surface of red blood cells that are infected by the malarial parasite Plasmodium falciparum. PfEMP1 is synthesized during the parasite's blood stage inside the RBC, during which the clinical symptoms of falciparum malaria are manifested. Acting as both an antigen and adhesion protein, it is thought to play a key role in the high level of virulence associated with P. falciparum. It was discovered in 1984 when it was reported that infected RBCs had unusually large-sized cell membrane proteins, and these proteins had antibody-binding (antigenic) properties. An elusive protein, its chemical structure and molecular properties were revealed only after a decade, in 1995. It is now established that there is not one but a large family of PfEMP1 proteins, genetically regulated (encoded) by a group of about 60 genes called var. Each P. falciparum is able to switch on and off specific var genes to produce a functionally different protein, thereby evading the host's immune system. RBCs carrying PfEMP1 on their surface stick to endothelial cells, which facilitates further binding with uninfected RBCs, ultimately helping the parasite to both spread to other RBCs as well as bringing about the fatal symptoms of P. falciparum malaria.

Paleoproteomics is a relatively young and rapidly growing field of molecular science in which proteomics-based sequencing technology is used to resolve species identification and evolutionary relationships of extinct taxa. While complementary to paleogenomics in application, the study of ancient proteins has the potential to reveal older, more complete phylogenies due to the relative stability of amino acids in proteins as compared to the nucleic acids of DNA. Ancient protein studies can further reveal types and sources of recovered tissues, as well as the developmental stages of fossilized specimens. Paleoproteomics can also be extended to archaeological materials such as textiles, animal skins, food remains, and pottery.

References

  1. 1 2 3 4 5 Wick, Georg; Kalischnig, Gerlinde; Maurer, Herbert; Mayerl, Christina; Muller, Pia Ulrike (2001). "Really old - Palaeoimmunology: Immunohistochemical analysis of extracellular matrix proteins in historic and pre-historic material". Experimental Gerontology. 36 (9): 1565–1579. doi:10.1016/s0531-5565(01)00141-3. PMID   11525878.
  2. 1 2 3 Schweitzer, M. H.; Chiappe, L.; Garrido, A. C.; Lowenstein, J. M.; Pincus, S. H. (2005). "Molecular preservation in Late Cretaceous sauropod dinosaur eggshells". Proceedings of the Royal Society B. 272 (1565): 775–784. doi:10.1098/rspb.2004.2876. PMC   1599869 . PMID   15888409.
  3. 1 2 3 Miller, R. L. (1994). "Diagnosis of Plasmodium falciparum infections in mummies using the rapid manual ParaSight™-F test". Transactions of the Royal Society of Tropical Medicine and Hygiene. 88: 31–32. doi:10.1016/0035-9203(94)90484-7.
  4. 1 2 3 Massa, Emma Rabino; Cerutti, Nicoletta; Savoia, A. Martin D. (2000). "Malaria In Ancient Egypt: Paleoimmunological Investigation On Predynastic Mummified Remains". Chungara: Revista de Antropología Chilena . 32 (1): 7–9. doi: 10.4067/s0717-73562000000100003 . JSTOR   27802107.
  5. 1 2 Semal, Patrick; Orban, Rosine (1995). "Collagen Extraction from Recent and Fossil Bones: Quantitative and Qualitative Aspects". Journal of Archaeological Science. 22 (4): 463–467. doi:10.1006/jasc.1995.0045.
  6. 1 2 Kacki, Sacha; Rahalison, Lila; Rajerison, Minoarisoa; Ferroglio, Ezio; Bianucci, Raffaella (2011). "Black Death in the rural cemetery of Saint-Laurent-de-la-Cabrerisse Aude-Languedoc, southern France, 14th century: immunological evidence". Journal of Archaeological Science. 38 (3): 581–587. doi:10.1016/j.jas.2010.10.012.
  7. Shiff, C. J.; Premji, Z.; Minjas, J. N. (1993). "The rapid manual ParaSight®-F test. A new diagnostic tool for Plasmodium falciparum infection". Transactions of the Royal Society of Tropical Medicine and Hygiene. 87 (6): 646–648. doi:10.1016/0035-9203(93)90273-s.