Pathogenesis of Common Childhood Viral Diseases PDF

PATHOGENESIS OF COMMON CHILDHOOD VIRAL DISEASES - Report on the basic viral taxonomy 2021 onwards virus needs binomial nomenclature Virus: - Broad term - Infectious at all stages - Taxonomic classification Virion: - Complex and complete manifestation - Viral genome + capsid + en...

PATHOGENESIS OF COMMON CHILDHOOD VIRAL DISEASES - Report on the basic viral taxonomy 2021 onwards virus needs binomial nomenclature Virus: - Broad term - Infectious at all stages - Taxonomic classification Virion: - Complex and complete manifestation - Viral genome + capsid + envelope - Transmitted form Pleomorphism: - Helical - Spherical - Polyhedral - Complex Viral characteristics: - Obligatory intracellular parasites Viral structure: - Viral attachment proteins - Envelope - Matrix protein - Overview key principles in the pathogenesis of viral disease Lytic cycle:  **Attachment**: The virus attaches to the surface of a specific host cell using proteins that bind to receptors on the cell\'s surface.  **Entry**: The virus injects its genetic material (DNA or RNA) into the host cell.  **Replication**: The viral genetic material takes over the host cell\'s machinery, directing it to make viral components like proteins and new copies of the viral genome.  **Assembly**: New viral particles are assembled from the replicated genetic material and proteins within the host cell.  **Lysis and Release**: The host cell bursts (lyses), releasing new virus particles that can go on to infect other cells. Lysogenic cycle:  **Attachment and Entry**: The virus attaches to a host cell and injects its genetic material (DNA or RNA) into the cell.  **Integration**: The viral DNA integrates into the host cell\'s DNA, becoming a **prophage** (in bacteriophages) or **provirus** (in other organisms).  **Dormancy**: The viral DNA remains inactive and is copied along with the host DNA as the cell divides. This way, the virus\'s genetic material is passed on to daughter cells without causing damage.  **Activation**: Under certain conditions (like stress or UV light), the viral DNA may be triggered to exit the host DNA and enter the **lytic cycle**. The virus then begins replicating and assembling, eventually causing cell lysis. Acute infection: - Recovery - Progression to chronic - Death Chronic: - Silent infection for life - Long silent period before disease - Reactivation - Relapses + exacerbation - Neoplastic changes - Describe how cells may respond to viral infection **Detection of Viral Infection** - **Pattern Recognition Receptors (PRRs)**: Cells use specialized receptors, like **Toll-like receptors (TLRs)** and **RIG-I-like receptors**, to detect viral molecules, such as viral RNA or DNA. PRRs are located on the cell surface or within cellular compartments, allowing them to detect viral presence promptly. **2. Antiviral Interferon Response** - **Interferon Production**: Upon detecting viral material, infected cells release **type I interferons** (IFN-α and IFN-β). Interferons act as signaling molecules that alert neighboring cells to the infection and initiate antiviral defenses. - **Antiviral State in Neighboring Cells**: Interferons bind to receptors on nearby cells, activating genes that inhibit viral replication. This creates an "antiviral state" in surrounding cells, making it harder for the virus to spread. **3. Inhibition of Viral Replication** - **Antiviral Proteins**: Interferon signaling activates the production of **antiviral proteins** in both infected and neighboring cells. These proteins, such as **protein kinase R (PKR)** and **RNase L**, interfere with viral replication by degrading viral RNA, inhibiting protein synthesis, or modifying cellular processes that viruses rely on. **4. Activation of Apoptosis (Programmed Cell Death)** - **Apoptotic Response**: Many infected cells activate programmed cell death (apoptosis) in response to viral infection. By undergoing apoptosis, the cell sacrifices itself to prevent the virus from replicating further. This is regulated by proteins like **p53** and caspases, which initiate and execute the cell death program. - **Cytotoxic T Cell-Induced Apoptosis**: **Cytotoxic T cells** (a part of the adaptive immune response) recognize viral peptides presented on the surface of infected cells and induce apoptosis through the release of cytotoxic molecules (e.g., perforin and granzyme). **5. Autophagy** - **Autophagy Pathway**: Cells can use **autophagy**, a process that involves engulfing and degrading parts of the cytoplasm, including viral particles. This helps contain the virus within cellular compartments, where it can be degraded and presented to the immune system. **6. Antigen Presentation to Activate Immune Cells** - **MHC Presentation**: Infected cells display viral peptides on their surface using **major histocompatibility complex (MHC) molecules**. This presentation is crucial for activating immune cells, such as **helper T cells** (which coordinate the immune response) and **cytotoxic T cells** (which target infected cells). - **NK Cell Activation**: Some viruses interfere with MHC presentation to avoid detection, but **natural killer (NK) cells** can recognize cells with low MHC expression and target them for destruction. **7. Production of Inflammatory Cytokines** - **Cytokine Release**: Infected cells and immune cells release **cytokines** like interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interferons to amplify the immune response. This attracts more immune cells to the site of infection, enhancing the body's ability to contain and eliminate the virus. - Describe general features of the course of viral infections **1. Entry and Incubation Period** - **Viral Entry**: Viruses enter the body through mucosal surfaces (like the respiratory tract, digestive tract, or urogenital tract), breaks in the skin, or via direct inoculation (such as insect bites or injections). - **Incubation Period**: This is the time between viral entry and the appearance of symptoms. During this period, the virus begins replicating within the host cells, usually without causing noticeable symptoms. The length of incubation varies depending on the virus and the host\'s immune response. **2. Prodromal Phase** - **Early Symptoms**: The prodromal phase is marked by the appearance of early, nonspecific symptoms (e.g., fever, malaise, body aches). These symptoms are often a result of the host's immune response, particularly the release of inflammatory cytokines like interferons. **3. Acute Phase** - **Peak Viral Replication**: During the acute phase, the virus replicates at a high rate, and specific symptoms related to the virus appear. This phase is characterized by tissue damage, immune response, and symptoms like cough, rash, or diarrhea, depending on the target cells and organs. - **Host Immune Response**: The innate immune system is active, releasing interferons and activating natural killer (NK) cells, while the adaptive immune response begins to ramp up, with T cells and antibodies targeting the virus. - **Symptom Severity**: Symptoms may range from mild to severe, and in some cases, life-threatening complications may arise if vital organs are affected (e.g., viral pneumonia, encephalitis). **4. Resolution or Persistence** - **Resolution**: In many cases, the immune system successfully eliminates the virus. **Cytotoxic T cells** kill infected cells, while **antibodies** neutralize free virus particles. Symptoms gradually resolve, and the host returns to health. - **Persistence**: Some viruses evade the immune system, leading to **chronic infections** (e.g., hepatitis B and C, HIV). These viruses may establish long-term infections by hiding within host cells or mutating to escape immune detection. Chronic infections can lead to long-term health issues or complications. **5. Latency and Reactivation (for Some Viruses)** - **Latency**: Certain viruses (e.g., herpesviruses) can enter a **latent phase** after the initial infection, where the viral genome remains dormant in specific cells (like neurons) without active replication or symptoms. - **Reactivation**: Under stress or immune suppression, latent viruses can reactivate, leading to recurrent symptoms or viral shedding. This is seen in infections like herpes simplex virus (cold sores) and varicella-zoster virus (shingles). **6. Immunity and Memory** - **Adaptive Immunity**: Following resolution, **memory T and B cells** remain in the body, ready to respond quickly if the virus reappears. This memory response can provide long-lasting immunity and is the basis of vaccination. - **Variable Immunity**: Immunity duration varies---some viruses (like measles) confer lifelong immunity, while others (like influenza) require repeated exposure or vaccination due to frequent mutations. - Introduce key elements of the biological responses to viral infections **1. Innate Immune Response (First Line of Defense)** - **Recognition of Pathogens**: - **Pattern Recognition Receptors (PRRs)**: Cells like macrophages, dendritic cells, and natural killer (NK) cells use PRRs (such as Toll-like receptors) to recognize viral components (e.g., viral RNA or DNA). This recognition triggers early immune responses. - **Interferons (IFNs)**: - Infected cells release **type I interferons (IFN-α and IFN-β)**, which signal neighboring cells to produce antiviral proteins that inhibit viral replication. Interferons also enhance the activity of NK cells and activate other immune cells. - **Natural Killer (NK) Cells**: - NK cells identify and destroy infected cells by recognizing changes in cell surface markers. They release cytotoxic molecules to kill infected cells, helping to control viral spread early on. - **Inflammation**: - Cytokines released by immune cells increase **inflammation**, which attracts additional immune cells to the site of infection. This inflammatory response helps contain the virus but can also contribute to symptoms like fever and tissue damage. **2. Adaptive Immune Response (Specific and Long-Lasting)** - **Activation of T Cells**: - **Helper T Cells (CD4+ T Cells)**: These cells recognize viral antigens presented by antigen-presenting cells (APCs) and secrete cytokines that help coordinate the immune response. - **Cytotoxic T Cells (CD8+ T Cells)**: Once activated, they seek out and kill virus-infected cells by recognizing viral peptides presented on the cell surface, which helps clear the infection. - **B Cells and Antibody Production**: - **B Cells** recognize viral antigens and, with helper T cell assistance, differentiate into **plasma cells** that produce specific antibodies. Antibodies can neutralize viruses by binding to them and preventing them from entering host cells. They also label viruses for destruction by other immune cells. - **Memory Cells**: - After the infection is cleared, some T and B cells remain as **memory cells**. These cells provide long-term immunity, allowing the body to respond faster and more effectively if the virus is encountered again. **3. Viral Evasion Mechanisms** Viruses often evolve mechanisms to evade or suppress the immune system, such as by **mutating** to escape recognition, **blocking interferon signaling**, or **hiding** within host cells. This can lead to chronic infections or recurrent infections in the case of some viruses. - Recognise oral features of the 'common viral infections of childhood', cold, flu, COVID-19, measles, mumps, rubella, chicken pox, other herpetic infections etc. HPV: - Human papillomavirus - Benign neoplasia - \>70 types (many not all cause warts) - dsDNA - non-enveloped virus - not lytic necessarily but can become lytic with virions to become transmissible - cancer related to virus causes DNA dmg -\> increased expression of oncoproteins E6 + E7 -\> inhibit apoptosis - spread by contact/auto-inoculation - long incubation period -\> up to 12 months for wart to appear - 50% disappear in 6months, 90% in 2 years - Foot (verruca) and finger warts common in children - Oral = squamous papilloma -\> shouldn't be present in children Common cold: - \>100 viruses - Rhinovirus most common - ssRNA - non-enveloped - spread by direct contact/droplets - lytic replication - children main carriers - paramyxoviridae -\> 3 types; paramyxovirus, pneumovirus, morbillivirus - adenovirus; common virus causing flu-like symptoms - orthomyxovirus = influenza A, B, C influenza: - orthomyxovirus - ssRNA - enveloped virus - lysogenic cycle - parainfluenza virus - respiratory syncytial virus (RSV) - enterovirus - types A and B have emergence of new strains SARS-CoV-2: - ssRNA - enveloped virus - symptoms less severe in children - spread by contact/droplets - lysogenic cycle - ulcers, 'COVID-tongue', ulcers, erosions, bullae, vesicles, mucosal pustules, macules, papules and pigmentations, haemorrhgic manifestations, crusts, spontaneous bleeding hand foot and mouth -- picornavirus, ssRNA non-enveloped virus rubella -- rubivirus, enveloped ssRNA virus measles -- paramyxovirus, enveloped ssRNA virus mumps -- paramyxovirus, enveloped -ssRNA virus chicken pox -- varicella, enveloped dsDNA virus