Basic Pathology: Infectious Diseases PDF

Basic Pathology: Infectious Diseases Norsyuhada Alias, P hD How Pathogens Cause Disease? 3 1 2 Enter host cells = infection/ tissue damage...

Basic Pathology: Infectious Diseases Norsyuhada Alias, P hD How Pathogens Cause Disease? 3 1 2 Enter host cells = infection/ tissue damage Induce host immune Release toxins = kill the cells responses= tissue Release enzymes= tissue damage to the host component degradation/ damage of blood vessels - restrict blood supply - necrosis Mechanism of Viral Injury Mechanisms of Viral Injury Viral injury ○ the damagecaused to host cells as a result of viral infections. ○ vary : type of virus, the host cell involved, and the stage of infection. Viruses can directly damage host cells by entering them and replicating at the host’s expense. Viral infection is influenced by… How? ---- > Tissue tropism 1. T he presence of viral receptors on host cells. 2. T he presence of specific transcription factors in the host cell. 3. P hysical circumstances. 4. Cytopathic effects. 5. Antiviral immune responses. 6. T ransformation of infected cells into benign or malignant tumor cells. Tissue Tropism T he range of cells and tissues of a host that support growth of a particular pathogen, such as a virus, bacterium or parasite. T he selective preferenceor affinity of a pathogen for specific types of host cells or tissues within the body. Some bacteria and viruses have a broad tissue tropism and can infect many types of cells and tissues.  The presence of viral receptors on Virus cell surface proteins host cells Influenza virus Normal receptors of the host Sialic acid residue The presence of specific transcription factors in the host cell T he presence of cell type-specific transcription factors that recognize viral enhancer and promoter elements. Eg: Human polyomavirus 2 (J C virus) replicates specifically in oligodendroglia in the CNS, because the promoter and enhancer DNA sequences that regulate the viral expression are active in glial cells. Physical circumstances- temperature Eg. Rhinoviruses infect cells only within the URT because they replicate optimally at the lower temperatures. Physical circumstances- chemicals Eg. Enteroviruses replicate in the intestine - they can resist in activation by acids, bile and digestive enzymes. Cytopathic Effect (CPE) - visible morphological changes in cell cultures due to viral infection. W hen viruses infect host cells, they often induce alterations in the morphology, structure, and function of the infected cells. T hese changes can be observed under a microscope and are collectively termed cytopathic effects. Cytopathic effects are commonly observed in virology laboratories when studying viral infections in cell cultures. Researchers use these effects as indicators of viral presence and activity. Key features of cytopathic effects include: 1. Cell Morphology Changes 2. Cell Lysis 3. Syncytium F ormation 4. Inclusion Bodies 5. Nuclear Changes 6. Altered Cellular F unctions Source: https://www.slideserve.com/Ava/immune-response-to-virus Key features of cytopathic effects include: 1. Cell Morphology Changes: ○ Viral infection can lead to various alterations in the shape and structure of host cells. ○ This may include cell rounding, shrinkage, enlargement, and the formation of cellular inclusions. 2. Cell Lysis: ○ Some viruses cause the destruction or lysis of infected cells. ○ This is often associated with the release of newly formed viral particles, which can go on to infect neighboring cells. ○ The destruction of cells can be observed as areas of cell death in a tissue culture. 3. Syncytium Formation: ○ In certain viral infections, infected cells may fuse with neighboring cells, forming multinucleated giant cells known as syncytia. ○ This can be seen in some viral infections, including certain paramyxoviruses and retroviruses. 4. Inclusion Bodies: ○ Viral replication may lead to the formation of characteristic structures called inclusion bodies within the infected cells. ○ Inclusion bodies are often composed of viral proteins and nucleic acids and can be visualized using microscopy. 5. Nuclear Changes: ○ Viral infections can cause changes within the cell nucleus, such as chromatin condensation, margination, or the formation of viral replication centers. ○ These nuclear changes are indicative of the host cell's response to viral replication. 6. Altered Cellular Functions: ○ Viral infection can interfere with normal cellular functions, including protein synthesis, DNA replication, and cellular metabolism. ○ The disruption of these processes contributes to the overall cytopathic effect.  Antiviral immune responses Tissue preference of a virus shapes how the immune system detects and fights the infection , with different responses in different tissues to eliminate the virus and minimize damage. Viral proteins on the surface of host cells may be recognized by the immune system  lymphocytes may attack virus- infected cells. Eg. Acute liver failure is accelerated by cytotoxic T lymphocytes (CT Ls) during hepatitis B infection  normal response to clear the infection/ to destroy infected hepatocytes but at the same time cause tissue injury. Note: Cytotoxic T lymphocytes (CTLs) = important for defense against viral infections, but it can also be responsible for tissue injury. Hepatocytes = the main functional cells of the liver. Transformation of infected cells into benign or malignant tumour cells - The specific tissues or cells targeted by a virus determine where it can potentially cause cancer. Virus -host interaction : Viruses with oncogenic potential infect specific tissues or cell types due to the presence of receptors or favorable conditions for viral replication. F or example: Human papillomavirus (HPV) targets epithelial cells in the cervix, leading to cervical cancer. Hepatitis B and C viruses target liver cells (hepatocytes), which can result in liver cancer. Tissue-specific tumour formation : T he tropism of a virus determines the type of cancer it may cause. F or example: HP V causes tumours in squamous epithelial cells, often in the cervix, throat, or anus. Mechanism of Bacterial Injury Mechanisms of Bacterial Injury 1. Bacterial virulence. 2. Bacterial adherenceto host cells. 3. Virulence of intracellular bacteria. 4. Bacterial toxins. Bacterial Virulence Pathogenicity islands Bacterial damage to host tissues depends on the ability of the bacteria to adhere to host cells, invade cells and tissues, or deliver toxins. Plasmids Mobile genetic elements that Bacterial virulence encode virulence factors Bacteriophages (Viruses) Mobile genetic elementsare pieces of DNA that can move from one location to another within a genome or between genomes. T hey play a key role in genetic diversity, evolution, and the spread of traits, including virulence Transposons factors and antibiotic resistance among bacteria.  Bacterial Virulence (disease producing power of an organism, the degree of pathogenicity ) Pathogenicity Islands (PAIs) carry genes encoding one or more virulence factors, including, but not limited to, adhesins, toxins, or invasins. may be located on a bacterial chromosome or may be acquired through horizontal gene transfer by plasmid, phage or transposon. cause non-invasive species to be pathogenic species. range from 10-200 kb. Eg. Salmonella sp.  has at least 5 P AIs  Activation of host signaling pathways in Salmonella host cells via delivery of SP I-1 virulence factors (yellow boxes) Salmonella Pathogenicity Island -1 (SPI -1) contains more than 28 genes that encode a complex bacterial type III secretion system (T 3SS), as well as secreted proteins and regulatory components. Source: https://www.cell.com/current-biology/fulltext/S0960-9822(99)80178-X Continue from previous page: Salmonella has invasive strategy which involves delivery of virulence factors to the host cytosol and induce cell ruffling on the host cell plasma membrane. T his way, Salmonella are able to ‘force feed’ themselves to host cells epithelium, giving them a place for replication and access to the underlying tissues. T hese secreted effectors (SoP ) modulate the functions of host cells and activate specific signalling cascades that result in the production of pro-inflammatory cytokines and intestinal inflammation. Note: Cell ruffling = the process where certain bacteria (or viruses) cause changes in the structure of the host cell's outer membrane (plasma membrane).  Conjugation in E.coli Plasmids P lasmid is a circular (most), double stranded DNA molecule that is not connected to the main bacterial chromosome and replicate independently. P lasmids act as the vector that transport the virulence genes from 1 host to another. Mechanism of gene transfer (horizontal): ○ Conjugation: a gene transfer process in which a recipient bacterium receives DNA from a donor bacterium by cell-to-cell contact through conjugative pili. ○ T ransformation: introduction, uptake and expression of foreign genetic material  Bacteriophages Viruses that infect bacteria  can influence the virulence of bacteria. Mechanism: T ransduction - the transfer of a DNA fragment from one bacterium to another by a bacteriophage. T ransduction can happen either by lytic cycle or lysogenic cycle based on the type of the bacteriophage ○ Generalized transduction ○ Lytic cycle - done by virulent bacteriophages in which bacterial cell is lysed when new bacteriophages are released. ○ Eg: Staphylococcus,Escherichia, Salmonella, and Pseudomonas ○ Specialized transduction ○ Lysogenic cycle - done by temperate bacteriophages in which bacterial cell is not lysed, and viral DNA integrates with bacterial DNA and survives in prophage stage within the bacteria for several generations, however, later may switch to lytic cycle under certain condition. ○ Eg: E. coli  GENERALIZED TRANSDUCTION Phage capsid accidently assembles around a small fragment of bacterial DNA→ phage injects the fragment of donor bacterial DNA it is carrying into the recipient during infection process → piece of the recipient's DNA is exchanged via homologous recombination  SPECIALIZED TRANSDUCTION Transposon T ransposons ("jumping genes") are small pieces of DNA that encode enzymes that enable the transposon to move from one DNA location to another, either on the same molecule of DNA or on a different molecule. T ransposons may be found as part of a bacterium's chromosome (conjugative transposons) or in plasmids. A transposon contains a number of genes, such as those coding for antibiotic resistance or other traits, flanked at both ends by insertion sequences coding for an enzyme called transposase. T ransposase is the enzyme that catalyzes the cutting and resealing of the DNA during transposition. Many conjugative transposons possess transfer systems that enables them to transfer DNA not only to like species, but also to unrelated species. Eg. E. coli Cut and paste Transposonsmove from one part of the genome to another. They are cut out from one location in the DNA and pasted into a new location. Two types of transposons under cut and paste: 1. transposons that carry its own excision enzyme (transposase). 2. transposons that depends on transposase made by another genefor its excision. Copy and paste Retrotransposons– RNA transposon (transcribe their DNA sequence into RNA  reverse-transcribed into DNA by the enzyme reverse transcriptase.) cDNA is then inserted back into the genome at a different location. T his "copy-and-paste" mechanism results in the production of a duplicate of the retrotransposon, which is integrated into a new part of the genome. Plasmids, bacteriophages, transposons P lasmids or bacteriophages can convert non pathogenic bacteria into virulent ones. P lasmids and bacteriophages are genetic elements that spread between bacteria and can encode virulence factors, including toxins, or enzymes that confer antibiotic resistance. Exchange of these elements between bacteria resulted in a survival advantage and/ or the capacity to causedisease. P lasmids, bacteriophages or transposons encoding antibiotic resistance can convert an antibiotic susceptible bacteria into a resistant one, making effective therapy difficult. Definition: P athogens: microorganisms that cause disease. P athogenicity: the ability of microbes to cause disease while virulence is the degree of pathogenicity. Virulence factor: the factor that enables an organism to invade a host and cause disease. Horizontal gene transfer: the transfer of genetic material from one organism to another one that is not its offspring; especially common among bacteria. Bacterial secretion systems: protein complexes present on the cell membranes of pathogenic bacteria functioned to secrete bacterial virulence factors (mainly of proteins) to invade the host cells.  Bacterial Adherence to Host Cells T he ability of bacteria to adhere to host cells is a critical factor in their ability to cause disease in a host organism. Adherence to host cells  the first step in the process of bacterial infection  a key role in the establishment of infection and the subsequent damageto host tissues. Eg. why bacterial adherence is important for pathogenicity: Delivery of virulence factors Adherence facilitates the delivery of virulence factors to host cells. Many pathogenic bacteria produce adhesins (proteins or structures that specifically bind to host cell receptors). Adhesins can serve as delivery mechanisms for other virulence factors, such as toxins or enzymes, directly impacting host cell function.  Example: Example: Streptococcus pyogenes E. coli, Neisseria gonorrhoeae Strains of E. coli express a specific pilus. Protein F and teichoic acid bind to N. gonorrhoeae has pili to adherence to host fibronectin on the surface of host cells and targets the host antibody response cells Virulence of Intracellular Bacteria Intracellular bacterial virulence refers to the ability of certain bacteria to invade and survive within the host's cells. Intracellular bacteria often use strategies to enter host cells, evade phagocytosis, and manipulate cellular processes to create a favourable environment for their survival. They may cause chronic or persistent infections. F acultative intracellular bacteria such as Shigella and enteroinvasive E. coli usually infect epithelial cells, while Mycobacteriumtuberculosisand Mycobacterium leprae infect macrophages, or they can infect both epithelial cells and macrophages such as Salmonella typhi. Example of intracellular bacteria: Mycobacterium tuberculosis, Chlamydia trachomatis, Salmonella spp., Listeria monocytogenes. Bacterial Toxins Any bacterial substance that contributes to illness. Classification: ○ Endotoxins - components of the bacterial cell. Lipopolysaccharide (LP S). ○ Exotoxins - proteins that are secreted by the bacterium. Classification based on their mechanism and site of action. Eg. Enzymes, superantigens, neurotoxins, enterotoxins Some of the role of bacterial toxins in host injury: Cell Membrane Damage: Many bacterial toxins target the host cell membrane, leading to its disruption. This can result in increased permeability, leakage of cellular contents, and ultimatelycell lysis. For example, toxins produced by bacteria likeStaphylococcus aureusand Streptococcus pneumoniae. Inhibition of Protein Synthesis: Some bacterial toxins interfere with host cell protein synthesis. F or example, the exotoxin produced by certain strains of Escherichia coli, known as Shiga toxin. Toxic Shock: Certain bacterial toxins can lead to systemic effects, causing conditions such as toxic shock syndrome. T oxins produced by Staphylococcus aureusand Streptococcus pyogenes can enter the bloodstream, leading to widespread inflammation, organ dysfunction, and potentially life- threatening systemic effects. Tissue Necrosis: Certain toxins have the ability to cause tissue necrosis (cell death) at the site of infection. Necrotizing toxins produced by bacteria like Clostridium perfringens contribute to tissue destruction and can lead to severe and rapidly progressing infections. Learning Outcomes: At the end of this lecture, it is expected that students should be able to explain the: 1. mechanism of viral injury. 2. mechanism of bacterial injury. THE END