Noun explanation of HLA

HLA (human leukocyte antigen) system is the most complex polymorphic system in human body. From the discovery of the first HLA antigen in 1958 to the 1970s, HLA has become an important emerging research field in immunology, immunology and biochemistry. Now, the composition, structure and function of its system have been basically clarified, and its physical and chemical properties and biological functions have also been clarified. These research results not only have important theoretical significance, but also have great biomedical value.

The essence and structure of 1 HLA

HLA is a highly polymorphic allogenic antigen, and its chemical essence is a glycoprotein, which consists of an α heavy chain (glycosylation) and a β light chain. The amino end of the peptide chain is outward (about 3/4 of the whole molecule), the carboxyl end goes deep into the cytoplasm, and the hydrophobic part in the middle is in the cell membrane. HLA can be divided into class I antigen and class II antigen according to its distribution and function.

Genetic control of 2 HLA

HLA is controlled by a gene cluster called Human Major Histocompatibility Complex (MHC). MHC is located on the short arm of chromosome 6.

The specificity of HALⅰⅰ antigen depends on α heavy chain, which is encoded by HLA-A, B and C sites. Its β light chain is β2- microglobulin, and its coding gene is on chromosome 15. HLA class ⅱ antigens are controlled by HLA-D region (including five subregions), in which A gene and B gene are encoded by α heavy chain and β light chain respectively, and the polymorphism of antigens depends on β light chain. The above genes (whose names were revised by WHO Nomenclature Committee 1975) are all polymorphic loci (multiple alleles) and are * * * dominant. If MHC is taken as a whole, its polymorphism is more prominent. It is conservatively estimated that there are at least 1300 different haplotypes, and correspondingly, there are about 17× 107 genotypes. This is the genetic basis of people who hardly have the same HLA except identical twins, so HLA can be regarded as an individual's "identity card".

Biological significance of 3 HLA

HLA is a polymorphic system, which has been preserved during the development of its species and has special biological significance.

3. 1 objective function

HLA antigens are distributed in all nucleated cells. Its antigen specificity lies in the specific amino acid sequence of peptide chain antigenic determinant. These antigens can be changed by foreign substances, such as some viruses or chemicals. When these gene products change, they become autoimmune and become the rake of immune rejection. It can be seen that the essence of rake function lies in "self-identification" to ensure the integrity of the body. Therefore, the distribution and polymorphism in all cells are very important.

3.2 Identification function

The recognition function of HLA actually refers to the unique synergy in immune response. Antibodies are produced in B cells, but in most cases, macrophages and T lymphocytes are needed. The process is as follows: after the antigen is treated by macrophages, the antigen information is transmitted to T helper cells, and then the T helper cells transmit the information to B cells to differentiate B cells into specific antibodies. In this process, T helper cells not only identify the antigen on sensitized macrophages, but also identify whether macrophages are consistent with their own class II antigens. That is to say, only when the haplotypes of macrophages and helper T cells are consistent, helper T cells will be activated, so that the immune response will be carried out under strict genetic control.

4 the medical value of HLA

4. 1 HLA and organ transplantation

The study of HLA was initially carried out under the impetus of organ transplantation. So HLA is also called transplantation antigen. Clinical practice shows that allograft rejection (except identical twins) should be the biggest obstacle to the success rate. In genetics, MHC is transmitted as a unit in Mendelian way. So there are three kinds of HLA-identical, semiidentical and fraternal. Practice has proved that more than 90% sibling donors with the same HLA are effective in kidney transplantation. Different haplotypes of donors, the effect is obviously reduced; Those with different haplotypes rarely survive. The revelation of the essence and function of HLA provides an important theoretical basis for transplantation matching. It can be said that organ transplantation is an important achievement of contemporary medicine.

4.2 As a genetic marker of some diseases

In 1972, Russel first reported that psoriasis patients carry HLA-B 13 or HLA-B 17. Since then, a large number of other diseases have been found to be related to specific HLA. Among them, HLA-B27 antigen is found in about 90% patients with ankylosing spondylitis, which makes HLA typing have diagnostic value and can even confirm the clinical differences between disease subtypes earlier. For example, psoriasis vulgaris is related to HLA, while pustular psoriasis is not related to HLA. Adolescent insulin-dependent diabetes mellitus is associated with HLA-B8, HLA-Bw 15 and HLA-B 18, but not with late-onset diabetes mellitus. Therefore, specific types of HLA have become genetic markers of some diseases. For example, autosomal recessive adrenal hyperplasia is due to the lack of 2 1- hydroxylase. Population association analysis and pedigree linkage analysis using HLA antigen polymorphism showed that two hydroxylase loci (2 1-OHA and 2 1-OHB) were closely linked with HLA-B and Dr. Therefore, HLA can be used for prenatal diagnosis. In eugenics, we can calculate the relative risk rate of children's illness for some diseases according to the existing data. On the other hand, the relationship between HLA and longevity has also become a research hotspot.

4.3 human leukocyte antigen and forensic medicine

Because of its high polymorphism, HLA has become the genetic marker that can best represent individual specificity and accompany individuals' lifelong stability, and the probability of the same HLA type among unrelated individuals is low. Forensic medicine identifies individuals by HLA genotype or phenotype detection, which is also an important means of paternity test because of its haplotype genetic characteristics.

High-level architecture

In1June, 1995, the modeling and simulation master plan (MSMP) formulated by the Office of Modeling and Simulation of National Defense (DMSO) put forward the same technical framework for future modeling/simulation. It includes three aspects: high-level architecture (HLA), conceptual model of task space (CMMS) and data standard (DS). Their common goal is to realize the interoperability between simulations and promote the reuse of simulation resources. Specifically, through the computer network, dispersed simulation components can run in a unified simulation time and simulation environment and can be reused. The basic idea of HLA is to design, develop and realize the object models of different levels and granularity of the system with object-oriented method, so as to obtain the interoperability and reusability of simulation components and simulation systems at a high level.

1August, 996, DMSO officially announced the definition and specification of HLA. After improvement and perfection, the rules, interface specifications and object model templates of HLA have been formally defined as IEEE 15 16, IEEE1516.1and IEEE15 by the American IEEE Standardization Committee on September 22nd, 2000. OMG, NATO M&A; S organization also adopts HLA as the standard.

1 HLA overview

The definition of HLA consists of three parts: (1) Object Model Template (OMT): it is a standardized description that defines objects, object attributes and the format and content of information interaction between objects in simulation. (2) Framework and rule set: HLA*** defines the 10 rule, and describes the responsibilities of simulation and federation members to ensure the correct interaction of simulation in a federation. The first five rules stipulate the requirements that the alliance must meet, while the last five rules are the conditions that the alliance members must meet. (3) Interface specification for federated members to access RTI: describe the simulation interaction mode during operation, provide the functional interface between federated members and RTI, and describe six types of services, * * *10/operation.

2 Object Model Template (OMT)

The object model in HLA is mainly used to describe two kinds of systems. One is to describe each federate, that is, to create a single HLA simulation object model (SOM). The other is used to describe the federate members who have the characteristics of information exchange with each other in a federation, that is, to create an HLA Federation Object Model (FOM). Whether describing SOM or FOM, the main purpose of OMT is to facilitate the interoperability of simulation systems and the reuse of simulation components.

As a template of object models, OMT provides a standard format and syntax for recording the contents of these object models. However, OMT itself does not explain how to build an object model and what OMT must record. OMT is one of the important mechanisms for HLA to achieve interoperability and reuse, which consists of the following table:

Object model identification table: used to record important information identifying HLA object model;

Object class structure table: used to record object classes and their parent-subclass relationships in Federation/Simulation;

Interactive class structure table: used to record interactive classes and their parent-subclass relationships in Federation/simulation;

Attribute table: used to describe the characteristics of object attributes in Federation/simulation;

Parameter table: used to explain the characteristics of interactive parameters in Federation/simulation;

Enumeration data type table: used to explain enumeration data types appearing in attribute table/parameter table;

Compound data type table: used to describe the compound data types appearing in the attribute table/parameter table;

Path space table: used to explain the path space of object attributes and interactions in a federation;

FOM/SOM dictionary: used to define all terms used in each table.

The above table must be used when describing the HLA object model of a federation or a single simulation system (federation member). In other words, OMT is suitable for federated object model (FOM) and simulated object model (SOM). An HLA object model must contain at least one object class or interaction class, but in some cases, some tables describing the object model may be empty.

3 HLA framework and rules

(1) federation should have a federation object model FOM, which should be compatible with OMT of HLA. FOM is a means to explain HLA federation data exchange, which records the agreements reached by federation members on the content, format and conditions of data exchange during federation operation.

(2) In a federation, all objects in FOM should belong to each member, not to RTI. In HLA, all the expressions of simulation-related object entities are put in federated members, not RTI, but RTI can have object instances in the Management Object Model (MOM).

(3) When the alliance is implemented, all data exchanges between members specified by FOM must be conducted through RTI. In HLA, the data of objects or interactive classes described by FOM are all data that may need to be exchanged between federated members, and the only way for members to exchange data is through the services provided by RTI.

(4) In federated execution, members should interact with RTI according to HLA interface specification, that is, access to RTI should follow interface specification.

(5) In joint execution, an object attribute can only be owned by one member at any given time. In HLA, different members can have different properties of the same object instance. In order to ensure the consistency of data in the whole federation, only one federation member can own (and therefore have the right to change) the properties of any given object instance at any given time.

(6) Federated members should have a member object model (SOM) conforming to the OMT specification. Federated members are usually composed of simulation systems that realize simulation functions. SOM describes the information that they need to obtain (order) and can provide (publish) to the outside world in order to realize their own simulation function.

(7) Members should be able to update and/or use the attributes of objects recorded in their SOM, and receive and send interactions recorded in SOM. The responsibility of each federate member is to publish the numerical values of the attributes of the objects that it is responsible for modeling to other members when the federate is running, and to receive the desired attribute data from other members with the help of the services provided by RTI.

(8) Members shall dynamically transfer and receive the ownership of attributes in federal execution according to the provisions in SOM. For HLA Federation, the realization of the actual simulation scene often needs the authority to dynamically transform the object attributes between specific Federation members. RTI provides corresponding services through "ownership management", and the concrete realization is the responsibility and cooperation between federal members.

(9) Members should update the conditions of object attributes specified in SOM (such as changing thresholds). HLA gives members who have the ownership of some object attributes the right to generate the ever-changing values of these attributes (often by solving the model), and it is responsible for publishing these attribute values continuously through RTI, so that other members who subscribe to these attributes can get the values of these attributes.

(10) Members should be able to manage local time to ensure that they can exchange data with other members of the federation in a coordinated manner. HLA provides a flexible time-marching simulation method for federate members through time management service, which enables HLA to be applied to continuous, discrete or mixed types of simulation. However, it requires federated members to manage their own logical simulation time.