Mechanisms of Antigenic Variation. : An Overview. Antigens undergo variations in two ways: (1) through DNA alterations introduced by errors in DNA (or RNA) replication or repair, recombination between nonidentical genes, and reassortment of gene segments and (2) through programmed variations that are also called phase variations, multiphasic antigenic variations, true antigenic variations, or antigenic variations.
What is antigenic variation?
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.
What is the mechanism for antigenic variation based on inversion?
Figure 1. Mechanism for antigenic variation based on sequence inversion. Gene inversion (A) changes the sequence directly downstream of the promoter. Promoter inversion (B) changes the orientation of the promoter, thereby changing the active gene sequence. The grey symbols represent triggers for the inversion mechanisms.
What is antigenic shift?
Antigenic shift: reassortment of the viral genome that occurs when a single host cells is infected with two viral cells. As the viral cells go through replication they reassort and the genes of the two species get mixed up and make 256 new variations of the virus. This occurs in influenza every couple of decades.
What are some examples of antigenic variation in parasites?
Antigenic variation is employed by a number of different protozoan parasites. Trypanosoma brucei and Plasmodium falciparum are some of the best studied examples. Trypanosoma brucei, the organism that causes sleeping sickness,
Which are mechanisms of antigenic variation quizlet?
Which are mechanisms of antigenic variation? Mutation, recombination, and gene switching all are forms of antigenic variation.
What is an example of antigenic variation?
Examples of random antigenic variation are those that occur in viruses such as the influenza virus and the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). The major antigenic components of these viruses are glycoproteins that make up their viral coat.
What is antigenic variation quizlet?
Definition of antigenic variation. Systematic changes or variations in proteins or other structures on the surface of pathogens to avoid elimination by the adaptive. Antigenic variation for. The avoidance of antibodies usually. It is a mechanism for extracellular pathogens or those that have an extracellular phase.
What are antigenic types?
The three broad ways to define antigen include exogenous (foreign to the host immune system), endogenous (produced by intracellular bacteria and virus replicating inside a host cell), and autoantigens (produced by the host).
What is antigenic variation simple?
Antigenic variation is one of the ways by which an infectious agent evades a host immune response. For example, a pathogenic bacterium could alter its surface proteins and carbohydrates so as to circumvent the immune response of the host.
Why does antigenic variation occur?
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.
Why can antigenic shifts cause pandemics quizlet?
Antigenic shift, on the other hand, occurs when the flu virus undergoes a major genetic alteration by acquiring different RNA strands. This change could result in a new potential pandemic strain.
What is antigenic variation in trypanosomes?
Trypanosome persistence in the mammal is due to antigenic variation, which involves changes in the identity of the variant surface glycoprotein (VSG) that forms a dense cell surface coat to shield invariant surface antigens from immune recognition.
What are B cells activated by?
B cells are activated when their B cell receptor (BCR) binds to either soluble or membrane bound antigen. This activates the BCR to form microclusters and trigger downstream signalling cascades.
What are 4 types of antigens?
There are different types of antigens on the basis of origin:Exogenous Antigens. Exogenous antigens are the external antigens that enter the body from outside, e.g. inhalation, injection, etc. ... Endogenous Antigens. ... Autoantigens. ... Tumour Antigens. ... Native Antigens. ... Immunogen. ... Hapten.
What are examples of antigen?
Antigens are known to trigger the immune system. They can be endogenous, exogenous, or autoantigens. Examples of antigens are pollen, bacteria, parasitic worms, and viruses.
What are the 4 different types of blood antigens groups?
The ABO system blood group A – has A antigens on the red blood cells with anti-B antibodies in the plasma. blood group B – has B antigens with anti-A antibodies in the plasma. blood group O – has no antigens, but both anti-A and anti-B antibodies in the plasma. blood group AB – has both A and B antigens, but no ...
Does influenza have antigenic variation?
The influenza viruses are unique among the respiratory tract viruses as they undergo significant antigenic variation. Both the surface antigens of the influenza A viruses undergo two types of antigenic variation: antigenic drift and genetic shift.
What is antigenic variation parasite?
Antigenic variation is a powerful survival strategy adapted by certain species of parasitic protozoa to allow them to survive in the immunized host. It is exemplified by the African trypanosomes, which provide far and away the best characterized and most studied system of this kind.
What is the difference between phase variation and antigenic variation?
The key difference between antigenic and phase variation is that antigenic variation is the mechanism that refers to the expression of antigenically distinct proteins, carbohydrate or lipids on their surfaces while phase variation is the high frequency reversible on and off switching of phenotype expression.
Does Plasmodium falciparum show antigenic variation?
Much of the success of Plasmodium falciparum in establishing persistent infections is attributed to immune evasion through antigenic variation. This process involves periodically exchanging variants of the major surface antigen PfEMP1, a protein also responsible for parasite cytoadherence.
What are the two categories of variation?
These mechanisms can be roughly divided into two categories: random variation and programmed variation (antigenic variation sensu stricto ).
How does inversion move genes?
This is the simplest way to move genes relative to a fixed location, and can involve either gene or promoter inversion (Figure 1). The inversion is catalyzed by a site-specific DNA recombinase that recognizes a short DNA segment flanking both sides of the invertible segment. A more sophisticated mechanism involves several segments that can be rearranged in different ways, yielding different products (Figure 2).
What is the cassette mechanism?
Also known as the cassette mechanism, as a gene is inserted behind a single promoter in an expression site like a cassette inserted into a tape recorder. The first cassette mechanism described involved a site-specific endonuclease, but whether a dedicated endonuclease is also involved in antigenic variation in African trypanosomes, the pathogen using this mechanism most extensively, is under debate. The high rate of switching and the limited sequence homology available for gene conversion suggests, but does not prove, the involvement of a dedicated endonuclease, but this enzyme remains to be found.
What is programmed variation?
Programmed variation refers to the existence of specific mechanisms to generate gene diversity. This generally implies a family of paralogous genes encoding proteins with the same or similar functions and the ability to express only one of the family members at a time. In effect this is achieved by maintaining only one active promoter at a time and/or moving genes to a position downstream of an active promoter. This can be accomplished either through recombination or through in situ control:
How do pathogens survive?
Foreign antigens are quickly and efficiently targeted by the host immune system, so in order to survive in this harsh environment, pathogens have evolved various ways to circumvent or disarm these defenses . Because the adaptive immune system uses a complex and time-consuming clonal selection process to develop cell lines with high binding specificity to the presented antigens, one way to temporarily outpace immune surveillance is to continually vary the conformation of antigenic determinants. For this strategy to work, the pathogen must present a tightly controlled antigenic profile to the host and maintain the ability to introduce antigenically distinct variants at regular intervals. In general mutation rates found in typical genomic sequences are insufficient to introduce enough variability to prevent formation of cross-reactive antibodies and immunity. Consequently a number of mechanisms have evolved that tend to promote localized variation within genes coding for immunodominant surface proteins.
Which type of recombination is used for genes near the telomeres?
Reciprocal recombination is used for genes near the telomeres (Figure 3), providing a versatile mechanism in pathogens with large numbers of chromosomes or linear plasmids, e.g. trypanosomes, Pneumocystis and Borrelia .
What is the translational control of gene expression?
Figure 7. Translational control of gene expression involves a change in the length of a short repeat sequence in the coding region. This change generates a premature stop codon, resulting in a non-functional protein.
Why is antigenic variation required every year?
A new vaccine is required every year because influenza virus has the ability to undergo antigenic drift.
Why is antigen variation important?
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 ...
How does VSG work?
In the early stages of invasion, the VSG coat is sufficient to protect the parasite from immune detection. The host eventually identifies the VSG as a foreign antigen and mounts an attack against the microbe. However, the parasite's genome has over 1,000 genes that code for different variants of the VSG protein, located on the subtelomeric portion of large chromosomes, or on intermediate chromosomes. These VSG genes become activated by gene conversion in a hierarchical order: telomeric VSGs are activated first, followed by array VSGs, and finally pseudogene VSGs. Only one VSG is expressed at any given time. Each new gene is switched in turn into a VSG expression site (ES). This process is partially dependent on homologous recombination of DNA, which is mediated in part by the interaction of the T. brucei BRCA2 gene with RAD51 (however, this is not the only possible mechanism, as BRCA2 variants still display some VSG switching).
How can antiviral antibodies be used to map antigenic evolution?
The ability of an antiviral antibody to inhibit hemagglutination can be measured and used to generate a two-dimensional map using a process called antigenic cartography so that antigenic evolution can be visualized. These maps can show how changes in amino acids can alter the binding of an antibody to virus particle and help to analyze the pattern of genetic and antigenic evolution. Recent findings show that as a result of antibody-driven antigenic variation in one domain of the H1 hemagglutinin Sa site, a compensatory mutation in NA can result leading to NA antigenic variation. As a consequence, drug resistance develops to NA inhibitors. Such a phenomenon can mask the evolution of NA evolution in nature because the resistance to NA inhibitors could be due to antibody-driven, HA escape.
How are antigenic properties determined?
The antigenic properties of influenza viruses are determined by both hemagglutinin and neuraminidase. Specific host proteases cleave the single peptide HA into two subunits HA1 and HA2. The virus becomes highly virulent if the amino acids at the cleavage sites are lipophilic. Selection pressure in the environment selects for antigenic changes in the antigen determinants of HA, that includes places undergoing adaptive evolution and in antigenic locations undergoing substitutions, which ultimately results in changes in the antigenicity of the virus. Glycosylation of HA does not correlate with either the antigenicity or the selection pressure. Antigenic variation may be classified into two types, antigenic drift that results from a change in few amino acids and antigenic shift which is the outcome of acquiring new structural proteins. A new vaccine is required every year because influenza virus has the ability to undergo antigenic drift. Antigenic shift occurs periodically when the genes for structural proteins are acquired from other animal hosts resulting in a sudden dramatic change in viral genome. Recombination between segments that encode for hemagglutinin and neuraminidase of avian and human influenza virus segments have resulted in worldwide influenza epidemics called pandemics such as the Asian flu of 1957 when 3 genes from Eurasian avian viruses were acquired and underwent reassortment with 5 gene segments of the circulating human strains. Another example comes from the 1968 Hong Kong flu which acquired 2 genes by reassortment from Eurasian avian viruses with the 6 gene segments from circulating human strains.
What is antigenic rift?
Antigenic rift: Recombination of viral gene. This occurs when there are again two viral cells that infect the same host cell. In this instance the viruses recombine with pieces of each gene creating a new gene instead of simply switching out genes. Recombination has been extensively studied in avian influenza strains as to how the genetics of H5N1 have changed over time.
What is the mechanism by which an infectious agent such as a protozoan, bacterium or virus alter?
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.
What is antigenic variation?
Antigenic variation is the multiphasic expression of antigenically different, but functionally conserved, molecules within a clonal population. This article describes representative examples of antigenic variation systems in human pathogens, including capsule switching in Neisseria meningitidis and Streptococcus pneumoniae, pilin antigenic variation in Neisseria gonorrhoeae, variant surface antigen (VSG) switching in Trypanosoma brucei, and antigenic drift and antigenic shift in influenza A viruses. Selection pressures of the host’s immune response can drive antigenic variability of surface molecules. Antigenic variants of many pathogens are problematic for vaccine design and remain a major reason for the inability to control some infectious diseases.
Why is antigenic variation important?
Antigenic variation of protozoans, bacteria and animal viruses provides a mechanism for persistence of the organism in its host, but makes immunological control difficult. The strategy used for the development of influenza A virus vaccines has been to identify the circulating strains early in the influenza season and to rapidly produce a vaccine against the predominant strains. In lentiviruses this strategy cannot be used because mutation and selection occur in a single infected host. Thus a wide repertoire of neutralizing epitopes must be included in a vaccine to prevent the evolution of lentiviruses that can evade the host immune response.
How do mutations occur in RNA?
There are several mechanisms that allow mutations to occur with sufficiently high frequency to be selected by antibodies. Viruses with an RNA genome show the highest degrees of antigenic variation. The mutations are not induced by antibody but are present in the population and can be selected out by antibodies when wild-type virus particles are neutralized. The origin of this rather high rate of mutation is the viral replicase. RNA polymerases have no 3′ editing function and so insertion of an occasional mismatched base is not corrected and quasispecies with random mutations are present in any RNA virus population. The mystery of RNA viruses is not why they show so much antigenic variation, but why some RNA viruses are antigenically almost invariant. Rhinoviruses exist in over 100 serotypes while poliovirus, another picornavirus, is stable enough that the vaccine did not need updating during the WHO Global Eradication campaign. Dengue virus exists in four serotypes and shows large variations in antigenic cross-reactivity within each serotype, but another flavivirus, yellow fever virus, is antigenically stable. Respiratory syncytial virus exists as two distinct antigenic groups with high antigenic diversity within each group, but other paramyxoviruses, such as measles, mumps, and rubella, are stable and therefore amenable to easier vaccination protocols.
Why do viruses have little antigenic memory?
As antibodies accumulate in the population against one serotype, another can move in because it is not neutralized by those antibodies. Presumably, there is little antigenic memory against these viruses, because even with > 100 serotypes of rhinoviruses, a person would eventually become exposed to all of them. Alternatively, the lack of immunity against all serotypes could be because the immune response focuses on single or a few immunodominant but non-crossreactive epitopes (a phenomenon known as original antigenic sin) or rapid clearance of the antigen may result in failure to achieve affinity maturation of the antibody response. Influenza viruses, on the other hand, are constantly evolving into new antigenic variants and the old ones do not return, with the exception of re-introduction of a 1950 H1N1 virus in 1977. It is not clear if other viruses, even very variable RNA viruses, undergo the same style of antigenic drift as influenza: a progressive, unidirectional evolution. The most variable virus of all is human immunodeficiency virus (HIV), the cause of AIDS. During HIV infection each infected individual generates a unique swarm of virus variants known as a quasispecies that continuously diversifies over the course of viral infection. For many virus species, the pattern of variation is not well understood, due to infrequent epidemics, geographic isolation, or lack of sufficiently extensive molecular analysis. Here we compare and contrast the antigenic variability of the most-studied viruses, influenza virus and HIV.
How does the immune system respond to viruses?
Immune responses to viruses are generally thought of as negative selection – that is, elimination or substantial reduction in replicative capacity of the pathogen. There are a few examples where immune recognition has a positive influence on the continued proliferation of the pathogen, due to viral mechanisms to exploit immune elimination. Some viruses can use Fc receptors or mannose receptors to internalize antibody-bound virus into a replication mode instead of a destructive one. Alternatively, the virus may sabotage the immune response by changing antigenicity. A primary basis of antigenic variation is selection of virus mutants by antibodies. These are known as escape mutants, and since the escaped virus is resistant to antibody neutralization it possesses a fitness advantage in the presence of antibody. Escape mutants may also be selected by CD4 + or CD8 + T cells. There is certainly variation in the T-cell epitopes, but a lack of definitive examples that these have been selected by T cells as an immune evasion mechanism in the same way as occurs with antibody selection.
What are some examples of random antigenic variation?
Examples of random antigenic variation are those that occur in viruses such as the influenza virus and the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). The major antigenic components of these viruses are glycoproteins that make up their viral coat.
Where did Eyav come from?
Alternatively, it has been also proposed that EYAV might have been derived from an ancestral virus introduced into Europe with the migration of ancestral lagomorphs (hares, rabbits) from North America through Asia. Lagomorph ancestors first appeared during the Eocene epoch (57.8–36.6 MYA) in what was then North America. They are thought to have first migrated into Asia during the Oligocene epoch (34–23 MYA) and by the high Miocene epoch (23–5 MYA) they were common in Europe. Genetic findings support the second hypothesis.
