Last edited: 8/8/2021 TOLL-LIKE RECEPTORS AND INTERFERONS Immunology: Inflammation: Toll-like Receptors and Interferons OUTLINE I) TOLL-LIKE RECEPTORS II) INTERFERONS III) REVIEW QUESTIONS IV) REFERENCES I) TOLL-LIKE RECEPTORS ● Proteins present in the cell membrane/vesicles inside the cells that respond to foreign pathogens → elicit specific responses ● Receptors expressed on WBCs like macrophages ● These receptors bind various pathogen associated molecular proteins (PAMPs) (1) PAMPs o Detail viral nucleic acids (RNA and DNA) o Lipopolysaccharide on bacteria o Flagellin on bacteria ● When these receptors are activated by these PAMPs o → triggers WBC to increase expression of nuclear factor kappa beta (NfKB) →↑ expression of proinflammatory cytokines such as: IL-1 Beta IL-18 TNF-alpha Interferons Medical Editor: Dr. Sofia Suhada M. Uzir II) INTERFERONS ● Proteins made by virus infected cells ● Functions: o Signal nearby host cells, let them know that there’s a virus in the vicinity→ make antiviral peptides o Alerting macrophages and natural killer cell to become activated and proliferate ● Virus infects cells o Triggers virus infected cell to express genes for interferon production ● Interferon (IFN) types o Alpha & beta IFNs o Gamma IFNs (A) ALPHA & BETA INTERFERONS ● Tell nearby healthy cells that there is a virus in the vicinity ● The nearby healthy cells than ↑ expression of antiviral peptides o If virus does infect healthy cells these antiviral nucleases will destroy viral nucleic acids ● These IFNs also cause cells to ↑ expression of viral antigens on MHC I molecules to activate cytotoxic T-cells (B) GAMMA INTERFERONS ● These are made by natural killer cells and T helper type 1 cells when stimulated by IL-12 from activated macrophages ● Actions: o ↑ activity of macrophages → ↑ phagocytosis of virus o ↑ activity of natural killer cells →↑cell killing of virus infected cells o ↑ expression of viral antigens on MHC II molecules for antigen presentation to trigger ↑ antibody production against virus Figure 1. PAMPs recognition by TLRs [Hindawi] Figure 2. Interferon functions [LSE] TOLL-LIKE RECEPTORS AND INTERFERONS IMMUNOLOGY: Note #1. 1 of 2 III) REVIEW QUESTIONS Which of the following IS NOT a proinflammatory cytokines? a. IL-1 beta b. TNF-alpha c. TNF-delta d. IL-18 Concerning PAMPs, which is true? a. The toll like receptors decrease its amount b. Lipopolysaccharide on RNA is an example c. Flagellin on virus is an example d. Flagellin on bacteria is an example Which of the following is not a type of interferons? a. Alpha b. Beta c. Gamma d. Delta Which of the following is true concerning the actions of interferons? a. Increase activity of macrophages b. Decrease expression of viral antigens on MHC II molecules c. Alerting nearby healthy cells to initiate apoptosis d. Alerting nearby healthy cells to release macrophages IV) REFERENCES ● Asa Cusack. The London School of Economics and Political Science. Interferon functions [Digital image] LSE ● Ji-Yoon Noh, Suk Ran Yoon, Tae-Don Kim, Inpyo Choi, Haiyoung Jung, "Toll-Like Receptors in Natural Killer Cells and Their Application for Immunotherapy", Journal of Immunology Research, vol. 2020, Article ID 2045860, 9 pages, 2020. [Digital image] https://www.hindawi.com/journals/jir/2020/2045860/ ● Le T, Bhushan V, Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017 ● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ: Pearson; 2020. ● Boron WF, Boulpaep EL. Medical Physiology.; 2017. ● Urry LA, Cain ML, Wasserman SA, Minorsky PV, Orr RB, Campbell NA. Campbell Biology. New York, NY: Pearson; 2020. ● Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's Principles of Internal Medicine. New York etc.: McGraw-Hill Education; 2018. ● lberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P . Molecular Biology of the Cell. New York, NY: Garland Science; 2002 ● Murphy K, Weaver C. Janeway's Immunobiology. Garland Science; 2016 ● Doan T, Melvold R, Viselli S, Waltenbaugh C. Immunology. Lippincott Williams & Wilkins; 2012 ● Levinson W. Review of Medical Microbiology and Immunology. Lange; 2012 Regarding alpha interferons, which is true? a. It is considered as the late acting interferons b. It helps in stimulating macrophages c. It works by attaching to gamma interferons d. It helps in activating cytotoxic T-cells Regarding gamma interferons, which is true? a. It directly activates cytotoxic T-cells b. It helps increase cell expression of viral antigens on MHC I molecules c. It is made by natural killer cells d. It doesn’t increase the activity of macrophages Interferons are special defense mechanism which operates by a. Binding to viruses b. Binding to neighboring cells c. Producing a long-lasting state of resistance d. Inhibiting virus induced enzymes Cytotoxic T-cells can be activated via which of the following? a. By reacting with budding viruses b. By identifying virus peptides presented by antibodies c. By identifying virus peptides presented by MHC I d. By releasing complement How are antibody producing cells stimulated? a. Interacting with a virus short peptide b. Interacting with a T helper cell c. Interacting with a plasma cell d. Interacting with a virus infected cell Which of the following is a characteristic of toll-like receptors? a. Cytoplasmic pattern recognition receptors b. Type 1 membrane proteins consisting of a recognition and signaling domain c. Highly conserved receptors involved in programmed cell death d. Promotes activation of the transcription factor NFAT (nuclear factor of activated T cells) CHECK YOUR ANSWERS 2 of 2 IMMUNOLOGY: Note #1. TOLL-LIKE RECEPTORS AND INTERFERONS