Disease resistance
!["This vein (4) shows the interaction between the malaria sporozoites (6) with sickle cells (3) and regular cells (1). While malaria is still affecting the regular cells (2), the ratio of sickle to regular cells is 50/50 due to sickle cell anemia being a heterozygous trait, so the malaria can’t affect enough cells with schizonts (5) to harm the body."[1]](/wiki/File:Sickle_Cell_genetic_resistance_to_Malaria.jpg)
Disease resistance is the ability to prevent or reduce the presence of diseases in otherwise susceptible hosts. It can arise from genetic or environmental factors, such as incomplete penetrance.[2] Disease tolerance is different as it is the ability of a host to limit the impact of disease on host health.
In crops this includes plant disease resistance and can follow a gene-for-gene relationship.
Genetic Factors
[edit]Incomplete Penetrance
[edit]An example of a genetic factor causing disease resistance is incomplete penetrance. Incomplete penetrance is the result of a genetic mutation not fully manifesting as the associated trait or disease. In the combined case of sickle cell anemia and malaria, individuals with one normal allele and one sickle cell allele, (heterozygous HbAS), are largely healthy due to incomplete penetrance.[3] They do not experience the effects of having sickle cell anemia, (due to the incomplete nature of the mutation), and gain resistance to malaria. This is due to the altered shape of their red blood cells due to the partial sickle cell trait, which impedes the Plasmodium parasite, giving the individual resistance to the associated infection and disease caused by the parasite.[3]
Specific Genes
[edit]Certain genes themselves provide disease resistance by directly enhancing the immune response or directly inhibiting pathogens. For example, the Mx1 gene directly encodes a protein that blocks the replication of some viruses, such as influenza, providing natural resistance in certain organisms (like mice).[4] Similarly, Toll-like receptors (TLRs), which are naturally occurring proteins, are critical in recognizing pathogen-associated molecules, (including microbial and viral threats), and triggering immune responses.[5] Notably, variations or specific alleles in these genes can strengthen the body’s ability to combat infections, showing how genetic traits can further contribute to innate immunity and pathogen resistance.
Hemoglobinopathies
[edit]Hemoglobinopathies are a class of monogenic disorders that impact the major red blood cell protein hemoglobin.[6] Hemoglobinopathies interfere either with hemoglobin production or change hemoglobin’s protein structure, respectively splitting them into the two categories of thalassemias and structural variants.[7] These disorders exist due to alpha- or beta-globin gene mutations,[6] causing symptoms of moderate to severe anemia, organ damage, and reliance on blood transfusion for survival. Hemoglobinopathies provide an uncommon resistance against malarial infection, allowing an increased fitness of these mutations in regions where the mortality risk of malaria is high.[7]
Hormonal Immunity
[edit]Sex hormones, otherwise known as gonadal steroid hormones, play a role in regulating immune system functions through their modulation of disease resistance and immune responses.[8] Levels of type-1 interferon (IFN-I) cytokines involved in the stimulation of immune response and tumor necrosis factors (TNF) proteins involved in an inflammatory immune response can be altered by the introduction of testosterone hormones by individuals undergoing masculinizing gender-affirming treatment.[9] Interferons are synthesized by plasmacytoid dendritic cells (pDCs) which have toll-like receptors (TLR-7) that modulate their activity, so with the introduction of testosterone downregulating TLR-7 production in pDCs, interferons are consequently downregulated.[9] Testosterone reduces the impact of IFN-I responses in pDCs while increasing the intensity of pro-inflammatory pathways involving TNF.[9]
See also
[edit]- Disease resistance breeding
- Plant disease resistance
- Gene-for-gene relationship
- Malaria
- Sickle cell disease
- MX1
- Toll-like receptor
- Hemoglobinopathy
References
[edit]- ^ Burt, Benjamin (June 3, 2016). "Sickle Cell genetic resistance to Malaria". Wikimedia Commons. Retrieved December 3, 2024.
- ^ MacArthur, Daniel (May 2016). "Superheroes of disease resistance". Nature Biotechnology. 34 (5): 512–513. doi:10.1038/nbt.3555. ISSN 1546-1696. PMID 27065009.
- ^ a b Uyoga, Sophie; Olupot-Olupot, Peter; Connon, Roisin; Kiguli, Sarah; Opoka, Robert O; Alaroker, Florence; Muhindo, Rita; Macharia, Alexander W; Dondorp, Arjen M; Gibb, Diana M; Walker, A Sarah; George, Elizabeth C; Maitland, Kathryn; Williams, Thomas N (September 2022). "Sickle cell anaemia and severe Plasmodium falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children Trial (TRACT)". The Lancet Child & Adolescent Health. 6 (9): 606–613. doi:10.1016/S2352-4642(22)00153-5. PMC 7613576. PMID 35785794.
- ^ Müller, M.; Brem, G. (September 1991). "Disease resistance in farm animals". Experientia. 47 (9): 923–934. doi:10.1007/BF01929883. ISSN 0014-4754. PMID 1915776.
- ^ Novák, Karel (January 2014). "Functional polymorphisms in Toll-like receptor genes for innate immunity in farm animals". Veterinary Immunology and Immunopathology. 157 (1–2): 1–11. doi:10.1016/j.vetimm.2013.10.016. PMID 24268689.
- ^ a b Lee, Young Kyung; Kim, Hee-Jin; Lee, Kyunghoon; Park, Sang Hyuk; Song, Sang Hoon; Seong, Moon-Woo; Kim, Myungshin; Han, Jin Yeong (2019-03-31). "Recent progress in laboratory diagnosis of thalassemia and hemoglobinopathy: a study by the Korean Red Blood Cell Disorder Working Party of the Korean Society of Hematology". Blood Research. 54 (1): 17–22. doi:10.5045/br.2019.54.1.17. ISSN 2287-979X. PMC 6439293. PMID 30956959.
- ^ a b Kohne, Elisabeth (2011-08-08). "Hemoglobinopathies". Deutsches Ärzteblatt International. 108 (31–32): 532–540. doi:10.3238/arztebl.2011.0532. ISSN 1866-0452. PMC 3163784. PMID 21886666.
- ^ Foo, Yong Zhi; Nakagawa, Shinichi; Rhodes, Gillian; Simmons, Leigh W. (2017). "The effects of sex hormones on immune function: a meta-analysis". Biological Reviews. 92 (1): 551–571. doi:10.1111/brv.12243. ISSN 1469-185X.
- ^ a b c Lakshmikanth, Tadepally; Consiglio, Camila; Sardh, Fabian; Forlin, Rikard; Wang, Jun; Tan, Ziyang; Barcenilla, Hugo; Rodriguez, Lucie; Sugrue, Jamie; Noori, Peri; Ivanchenko, Margarita; Piñero Páez, Laura; Gonzalez, Laura; Habimana Mugabo, Constantin; Johnsson, Anette (September 26, 2024). "Author Correction: Immune system adaptation during gender-affirming testosterone treatment". Nature. 634 (8033): E5–E5. doi:10.1038/s41586-024-08081-w. ISSN 1476-4687. PMC 11464365. PMID 39317781.
