Infection Recognition Molecules - Podcast Version TeachMePhysiology 0:00 / 0:00 1x 0.25x 0.5x 0.75x 1x 1.25x 1.5x 1.75x 2x Pathogens establish themselves in the body by breaching the innate immune system, then evading the adaptive immune system. Therefore, both systems have evolved to recognise pathogens, differentiating between ‘self’ and ‘non-self’. The innate immune system recognises pathogen-associated molecular patterns (PAMPs), leading to a rapid, non-specific immune response that includes inflammation and phagocytosis. The adaptive immune system recognises pathogens through specific antigens, leading to a more targeted immune response that includes the production of antibodies and the activation of cytotoxic T cells to eliminate infected cells. This article will discuss how the immune system recognises foreign cells through infection recognition molecules. Pro Feature - 3D Model You've Discovered a Pro Feature Access our 3D Model Library Explore, cut, dissect, annotate and manipulate our 3D models to visualise anatomy in a dynamic, interactive way. Learn More Pattern Recognition Receptors The immune system has evolved to recognize pathogens through specific molecules that are associated with infection. These molecules are known as pathogen-associated molecular patterns (PAMPs) and are recognized by pattern recognition receptors (PRRs) on antigen-presenting cells (APCs) such as macrophages and dendritic cells. PRRs are a diverse group of receptors that can recognize a wide range of PAMPs, including bacterial lipopolysaccharide and peptidoglycan, viral nucleic acid and fungal cell wall components. Unlike components of the adaptive immune system, PRRs are not specific to individual pathogens, but to groups of pathogens. Thus, they do not possess cellular memory. Major PRRs The main type of PRR is called Toll-like receptors (TLRs). There are 10 types of TLR in humans. In order to detect both extracellular (e.g. bacteria) and intracellular pathogens (e.g. viruses), TLRs are located on the cell surface and within endosomes intracellularly. Toll Like Receptor (TLR) PAMP Recognised Type of Pathogen TLR2 Peptidoglycan Gram Positive Bacteria TLR3 dsRNA Viruses TLR4 Lipopolysaccharide Gram Negative Bacteria TLR5 Flagellin Bacteria TLR7 ssDNA Viruses TLR9 dsDNA Viruses When a TLR recognizes a PAMP, it triggers a signalling cascade that leads to the production of cytokines and chemokines that results in activation of the immune response. This includes the recruitment of other immune cells to the site of infection, activation of phagocytosis and the presentation of antigens to T cells. Secreted PRRs The liver also produces a number of secreted PRRs as part of the acute phase response to infection. These can recognize PAMPs in the bloodstream and act as opsonins, meaning they can bind to pathogens and enhance their recognition and uptake by phagocytic cells. Examples include: mannose-binding lectin (MBL) – a member of the collectin family that acts as an opsonin by binding to mannose residues on the surface of pathogens. It also activates the lectin pathway of the complement system. C-reactive protein (CRP) – another opsonin that binds to phosphocholine on the surface of bacteria and damaged cells. It can activate the classical pathway of the complement system. CRP is used clinically as a marker of ongoing inflammation, though it is not specific for infection and can be elevated in other inflammatory conditions. Major Histocompatibility Complexes When a pathogen breaches the innate immune system, the adaptive immune system is activated. This involves: uptake of the pathogen by antigen-presenting cells (APCs) processing of the pathogen into smaller peptides (antigens) presentation of these antigens to T cells via MHC molecules on APC surface. The MHC is a set of genes that encode for cell surface proteins that present antigens to T cells. There are two main classes of MHC molecules: class I and class II. Created in BioRender Fig 1Structures of the MHC classes I and II molecules Note: All vertebrates possess an MHC, and the human MHC is also known as the human leukocyte antigen (HLA) system. Therefore, in humans, the terms MHC and HLA are interchangeable. Summary of differences between MHC class I and class II:  MHC class I MHC class II Expression All nucleated cells (including APCs) Professional APCs only (dendritic cells, macrophages, Langerhans cells, B cells) Antigens Processes and presents endogenous antigens (e.g. viruses) via endogenous pathway Processes and presents exogenous antigens (e.g. bacteria) via exogenous pathway T cells Presents antigens to CD8+ cytotoxic T cells Presents antigens to CD4+ helper T cells (This can be remembered as: 8 × I = 4 × II = 8) Response CD8+ T cell is activated. When it recognises the antigen presented by MHC class I, it kills the infected cell by cell-mediated cytotoxicity. CD4+ T cell is activated. When it recognises the antigen presented by MHC class II, it helps activate other immune cells, including: B cells to produce antibodies macrophages to enhance phagocytosis. Subtypes HLA-A, HLA-B and HLA-C HLA-DP, HLA-DQ and HLA-DR Clinical Relevance Septic Shock Endotoxin is a lipopolysaccharide located on the surface of gram-negative bacteria. It binds to Toll-like receptor 4 (TLR4) which stimulates macrophages and dendritic cells to release cytokines. Cytokines can trigger an inflammatory response and act on endothelial cells to cause vasodilation. This can be helpful in supplying immune cells and opsonins to the infected site. A severe infection can trigger an inappropriate widespread vasodilation causing septic shock. Untreated, the sudden drop in blood pressure results in hypoperfusion and multi-organ failure with a very high mortality rate. Clinical Relevance Organ Transplantation The MHC is highly polymorphic, meaning that there are many different alleles of MHC genes in the population, which allows for a wide range of immune responses to different pathogens. This polymorphism has implications for organ transplantation. Do you think you’re ready? Take the quiz below Pro Feature - Quiz Infection Recognition Molecules Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePhysiology Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Frequent questions What are pathogen-associated molecular patterns (PAMPs)? PAMPs are molecules found on pathogens that are recognised by the innate immune system, triggering a rapid and non-specific immune response. They include components like bacterial lipopolysaccharides and viral nucleic acids, which help differentiate between self and non-self. How do Toll-like receptors (TLRs) function in the immune response? TLRs are a type of pattern recognition receptor that detect specific PAMPs on pathogens, leading to the activation of immune responses. When TLRs recognise a PAMP, they initiate a signalling cascade that results in the production of cytokines and the recruitment of immune cells to the site of infection. What role do Major Histocompatibility Complex (MHC) molecules play in the immune system? MHC molecules present processed antigens from pathogens to T cells, activating the adaptive immune response. There are two classes of MHC: class I presents endogenous antigens to CD8+ T cells, while class II presents exogenous antigens to CD4+ T cells. What is the significance of secreted pattern recognition receptors in the immune response? Secreted pattern recognition receptors, such as mannose-binding lectin and C-reactive protein, enhance pathogen recognition by binding to PAMPs in the bloodstream. They act as opsonins, facilitating the uptake of pathogens by phagocytic cells and activating the complement system. How does septic shock relate to the immune response and pathogen recognition? Septic shock occurs when endotoxins from gram-negative bacteria bind to TLR4, causing excessive cytokine release and widespread vasodilation. This can lead to a dangerous drop in blood pressure and multi-organ failure if not treated promptly. Rate This Article