Immunology of malaria
David A Warrell, Herbert M Gilles in Essential Malariology, 2017
The relationship between malaria and the red cell has played a central role in the development of ideas on the selection of single genes by infective agents, but it seems certain that many other host genes will be important. Human leucocyte antigens (HLA) are a highly polymorphic family of proteins that play critical roles in the genesis of immune responses (see below). There is some evidence from studies in Sardinia of selection for particular HLA types in populations historically exposed to malaria when compared with populations of the same ancestral stock living at a higher altitude, where malaria has never been endemic. More recently, evidence has emerged for associations between a few HLA antigens common in African populations and protection from severe disease. An HLA class 1 antigen, HLA-BW53, and an HLA class 11 haplotype, DRBI*1302-DQB 1*0501, have been associated with reduced susceptibility to severe disease (Hill et al., 1991).
Autoimmune Disease
Gia Merlo, Kathy Berra in Lifestyle Nursing, 2023
An immune system that functions properly protects humans from invading hosts that cause disease or infection (Lerner et al., 2016). The immune system consists of proteins and cells that recognize invaders and implement an inflammatory response to destroy the invading pathogens. The immune system uses inflammation as a central component to eliminate pathogens and repair tissue (Kopp, 2019). Once activated, the immune system secretes pro-inflammatory cytokines, triggering the production of free radicals until the body is healed. The immune system recognizes pathogens as foreign due to a protein called human leukocyte antigen, which is present on the surface of every cell in the human body. A malfunctioning immune system will attack its own cells, leading to chronic inflammation, which leads to chronic disease.
Gynecological Cancer—Ovarian, Endometrial, Cervical
Peter G. Shields in Cancer Risk Assessment, 2005
Genetic Polymorphisms:Human leukocyte antigen polymorphisms: An individual’s level of immunity is one factor that may be associated with a woman’s risk of CIN III or invasive cervical cancer. Human leukocyte antigen (HLA) classes I and II genes, are known to be involved in the immune response (364). There are 20 class I genes in the HLA region, three of these, HLA-A, B, and C, are mainly involved in the immune response. Class I genes are expressed in most somatic cells and class II are expressed by a subgroup of immune cells including B cells, activated T cells, macrophages, dendritic cells and thymic epithelial cells. The function of both class I and II molecules is to present short peptides to T cells thereby initiate an immune response (391). A number of studies have shown an association between particular HLA polymorphisms and cervical neoplasia. Hildeshem et al. reported a ninefold increased risk of HSIL if a woman was homozygous for DQB1*302 or a carrier of both B7 and DQB1*(302,392,393). Neuman et al. reported a positive association, between HLA DQB1*0303 and the risk of invasive cancer, only among HPV positive patients (p = 0.005) (394). Cuzick et al. reported similar findings of increased risk but with different variants of HLADQB1 (395).
Human leukocyte antigen (HLA)-DRB1 allele polymorphisms and systemic sclerosis
Published in Modern Rheumatology, 2019
Yanzhen Xu, Nanfang Mo, Zhiwen Jiang, Shaoming Lu, Shien Fu, Xinyan Wei, Dong Zhao, Zhibin Xie, Wenxian Jia, Jiayi Liu, Xiao Wang, Dongchen Shi, Yang Jiao, Chengwu Liu, Xiaoli Yang
The human leukocyte antigen (HLA) gene, located on chromosome 6, is important for the regulation of the fundamental molecular and cellular processes of the immune system. It has been confirmed that the HLA gene is associated with more than 100 different diseases [16]. HLA genes are categorized into three basic groups: class I, class II, and class III [17]. Class I (HLA A, B, and C) molecules are expressed in almost all nucleated cells and are responsible for the presentation of endogenous antigens. Class II (HLA DR, DQ, and DP) molecules mainly exist in CD4+ T cells, presenting exogenous antigens [18,19]. HLA-DR molecules are heterodimers composed of an α chain and a β chain. The α chain is encoded by the DRA gene, which has no polymorphisms. The β chain is encoded by the DRB gene, which has many polymorphisms, including DRB1, DRB3, DRB4 and DRB5 [8]. The HLA gene is characterized by high gene density and, more importantly, the coding genes for these loci are in strong linkage disequilibrium, which makes it very difficult to confirm the association between these genes and the disease [20]. In studies comparing the HLA gene and SSc, results have revealed that HLA alleles are strongly associated with susceptibility for SSc [21,22]. Several studies have reported that HLA Class II DRB1 alleles have a significant association with SSc [23,24], however, this conclusion is currently still under debate.
HLA transgenic mice: application in reproducing idiosyncratic drug toxicity
Published in Drug Metabolism Reviews, 2020
Takeshi Susukida, Shigeki Aoki, Tomohiro Shirayanagi, Yushiro Yamada, Saki Kuwahara, Kousei Ito
Human leukocyte antigens (HLAs) are essential molecules ubiquitously expressed throughout the body. They are responsible for regulating the adaptive immune response by communicating with CD4+ or CD8+ T cells using peptide fragments that identify molecules as self or non-self (i.e. abnormal). HLAs can be roughly divided into 2 classes: class I molecules present endogenously processed peptides that target CD8+ T cells, while class II molecules are expressed on the surface of antigen-presenting cells, such as dendritic cells, macrophages, and B cells, which target CD4+ T cells (Redwood et al. 2018). HLA-mediated T cell activation is intended to protect our body from foreign substances, such as viruses, bacteria, drugs, and graft cells; however, excessive immune responses, represented as hypersensitivity reactions and autoimmune diseases, can severely damage organs. For example, the major histocompatibility complex (MHC) is associated with an autoimmune disease comprising HLA-B27 and ankylosing spondylitis, which was discovered in patients (Brewerton et al. 1973). Although this landmark observation provided beneficial insights into understanding onset risk, the fundamental mechanism of this association remained undetermined. Thus, researchers aimed to develop a novel approach to clarify the role of HLA molecules in autoimmune diseases.
Exploring Klebsiella pneumoniae capsule polysaccharide proteins to design multiepitope subunit vaccine to fight against pneumonia
Published in Expert Review of Vaccines, 2022
Jyotirmayee Dey, Soumya Ranjan Mahapatra, S Lata, Shubhransu Patro, Namrata Misra, Mrutyunjay Suar
The selected protein was submitted to IEDB MHC-II binding tool (http://tools.iedb.org/mhcii/) for 15-mer Helper T lymphocyte (HTL) epitope prediction [20] and their respective-binding alleles using the CONSENSUS method [21] considering human HLAs as a reference set by default. Twenty-seven human leukocyte antigens (HLA) were evaluated. The percentile rank threshold of ≤2 was used here to ensure accuracy. The server assigns IC50 values to the predicted epitopes, which are inversely related to the binding affinity toward the MHC-II. IC50 scores of <50 represent a high binding affinity. The IC50 value <500 nM corresponds to intermediate binding affinity; however, <5000 nM is related to the low binding affinity of epitopes toward MHC-II. The binding affinity of predicted epitopes toward the MHC-II is inversely related to the percentile rank. The lowest consensus scores of the peptides were chosen to be the best binders as according to the IEDB server, a lower percentile rank indicates higher affinity. The best candidates were further evaluated on NetMHCIIpan4.0 (http://www.cbs.dtu.dk/services/NetMHCIIpan/) server. NetMHCIIpan 4.0 server is a state-of-the-art method for the quantitative prediction of peptide binding to MHC class II molecule of known sequence. The parameters were set at default.
Related Knowledge Centers
- Chromosome 6
- Coeliac Disease
- Major Histocompatibility Complex
- Membrane Protein
- Type 1 Diabetes
- Immune System
- Autoimmune Disease
- Gene
- Base Pair
- Gene Polymorphism