LSM4223 Notes (1) PDF

### **Antimicrobial Strategies** - - 1. 2. 3. 4. 5. 6. ### **Antimicrobial peptides (AMPs)** - - - - ### **Phage therapy** - - - - - Pros: - - - Cons: - - - - - ### ### **Antisense oligonucleotides** - - - - - - ### **Anti...

### **Antimicrobial Strategies** - - 1. 2. 3. 4. 5. 6. ### **Antimicrobial peptides (AMPs)** - - - - ### **Phage therapy** - - - - - Pros: - - - Cons: - - - - - ### ### **Antisense oligonucleotides** - - - - - - ### **Antibiotics** ### **Mechanisms of Antibiotics** 1. - - - - - - - - **B-lactamase inhibitors** (e.g. clavulanic acid) - - - - - - - - - 2. - - - - - - - - 3. - - - - - - - - 1. - - ### **Resistance Mechanisms** 1. - - - 2. - 3. - - 4. - - ### **Key Antibiotics Overview** - - - - - ### **Important Questions** 1. 2. 3. 4. Lec 2: Laboratory Methods of Diagnosis in Microbiology ### **Diagnostic Microbiology Laboratory Overview** 1. - - - - - 2. - - - #### **Microscopy and Staining Techniques** 1. - - - - - - 2. - - - 3. - - 4. - - - 5. - - #### **Culture Methods** 1. - - - - - 2. - - 3. - 4. - #### **Non-Culture Methods** **Why would we choose these tests?** - - - - - 1. - - - - - - - - - - 2. - - - - - - - 3. - - - - - - - - - #### **Susceptibility Testing** 1. - - - 2. - - #### **Conclusion** - - - Lec 3: Microbial Pathogenesis ============================= #### **Microbe-Host Relationships** 1. Mutualism: Reciprocal benefits for both organisms. ================================================== - Example: Gut flora with 500--1,000 bacterial species (e.g., *E. coli* aids digestion). ====================================================================================== 2. Commensalism: One species benefits, the other is unaffected. ============================================================ - Example: Skin bacteria (e.g., *S. epidermidis*) consume waste products without harming the host. ================================================================================================ 3. Parasitism: Benefits the microbe but harms the host. ==================================================== - Basis of microbial pathogenesis. ================================ - Example: Smallpox virus causing systemic infection and rash. ============================================================ #### **Koch\'s Postulates & Rivers\' Modifications** 1. Koch's Postulates: ================== - Microbe must be present in all disease cases. ============================================= - Must be isolated and grown in pure culture. =========================================== - Disease must be reproducible in a healthy host when the pure culture is introduced. =================================================================================== - Microbe must be recoverable from the experimentally infected host. ================================================================== 2. Rivers' Modifications (for viral diseases): =========================================== - Virus isolated from diseased hosts, absent in healthy individuals. ================================================================== - Virus cultivable in laboratory host cells. ========================================== - Filterability proof confirms viral size. ======================================== - Disease reproducible in the original or related species. ======================================================== - Virus re-isolatable from inoculated hosts. ========================================== - Detectable specific immune response. ==================================== #### **Key Steps in Infectious Disease** 1. Attachment & Entry: =================== - Break protective barriers and bind to host receptors. ===================================================== 2. Multiplication: =============== - Increase in microbial numbers. ============================== 3. Evasion of Host Defenses: ========================= - Survival within host cells. =========================== 4. Exit & Spreading: ================= - Local infection: Spread to neighboring cells. ============================================= - Systemic infection: Spread via blood to other organs. ===================================================== - Horizontal transmission: Between individuals (e.g., respiratory droplets). ========================================================================== - Vertical transmission: Mother-to-child (e.g., HBV). =================================================== #### **Mechanisms of Harm** 1. Direct Mechanisms: ================== - Cytopathic Effects: =================== - Cell death and tissue damage. ============================= - Abnormal cellular structures (e.g., inclusion bodies). ====================================================== - Cell fusion or multinucleated cells. ==================================== - Activation of host cell-death pathways. ======================================= - Toxin Secretion: ================ - AB Toxins: Subunit A inhibits cellular functions; Subunit B binds to cell receptors. ==================================================================================== - Membrane-Damaging Toxins: Cause pore formation or disrupt membranes. ==================================================================== - Neurotoxins: Block nerve signals, causing paralysis (e.g., botulinum toxin, tetanus). ===================================================================================== 2. Indirect Mechanisms: ==================== - Immunopathology: ================ - Overactivation of the immune system (e.g., cytokine storm caused by LPS activating TLR4). ========================================================================================= - Antibody-Dependent Enhancement (ADE): ===================================== - Non-neutralizing antibodies from a prior infection facilitate infection by a related serotype. ============================================================================================== - Malignant Transformation: ========================= - \~18% of human cancers are linked to viral infections. ====================================================== - Persistent viral infection interacts with host tumor-promoting factors (e.g., HPV, HBV). ======================================================================================== #### **Acute vs. Chronic Viral Infections** - Acute: Rapid onset, short duration (e.g., Influenza A). ======================================================= - Chronic: Long-lasting infections with asymptomatic phases (e.g., HPV, HBV, HIV-1). ================================================================================== - Chronic infections increase cancer risk. ======================================== - Cancer-Causing Viruses: ======================= - Both DNA and RNA viruses (e.g., HPV, HBV). ========================================== - HPV vaccine targets high-risk subtypes to prevent cervical cancer. ================================================================== #### **Factors Affecting Disease Severity** 1. Microbe-Specific Factors: ========================= - Virulence factors aid in immune evasion (e.g., HA cleavage in Influenza A). =========================================================================== - Strain variations affect pathogenicity (e.g., H5N1 causes severe disease; seasonal flu is milder). ================================================================================================== 2. Host-Specific Factors: ====================== - Immune response strength. ========================= - Aging-related immune decline (immunosenescence). ================================================ - Changes in physical barriers and microbiota (e.g., reduced gastric acidity). ============================================================================ #### **Control Measures** 1. Vaccines: ========= - HPV vaccines prevent entry of high-risk subtypes into host cells. ================================================================= - HBV vaccine lowers risk of chronic infection in newborns. ========================================================= 2. Preventing Transmission: ======================== - Hygiene practices (e.g., masks for respiratory viruses). ======================================================== - Screening for carriers (e.g., HBV testing in blood donors). =========================================================== #### **Key Takeaways** - Microbial pathogenesis involves direct and indirect mechanisms. =============================================================== - Disease outcomes depend on microbe and host characteristics. ============================================================ - Vaccination and hygiene are critical in controlling disease spread. =================================================================== - Understanding Koch's and Rivers' criteria is essential for identifying pathogens. ================================================================================= Lec 4: Vaccines =============== #### **Basics of Vaccines** 1. - - - - - 2. - - #### **Characteristics of an Ideal Vaccine** 1. 2. 3. #### **Major Vaccine Types** 1. - - - 2. - - - 3. - - - 4. - - - 5. - - - #### **Vaccine Adjuvants** - - - - - #### **Vaccination Outcomes** 1. 2. 3. - -  #### **Vaccine Challenges** 1. - - 2. - - #### **Vaccine Side Effects** - - #### **Contraindications** - - - - #### **Future of Vaccine Development** 1. - 2. - 3. - 4. -  #### **Summary** - - - Lec 5: Opportunistic Infections =============================== **1. Overview of Opportunistic Infections** ------------------------------------------- - - - - - - - - - - **2. Specific Infections** -------------------------- ### **HIV and AIDS** - - - - - - - - - - - - - - - - ### **Candidiasis** - - - - - - - - - - - - - - - - ### **Pneumocystis jiroveci Pneumonia (PCP)** - - - - - - - - - - ### **Toxoplasmosis** - - - - - - - - - - - - ### **Cryptosporidiosis** - - - - - - - - - - - **3. General Strategies for Managing Opportunistic Infections** --------------------------------------------------------------- 1. - - 2. - 3. - Lec 6: New and Re-emerging Infections ===================================== **1. Emerging and Re-emerging Infectious Diseases (EIDs and RIDs)** ------------------------------------------------------------------- ### **Definitions** - - - - - - ### **Categories of EIDs** 1. - - 2. - - 3. - - **2. Factors Influencing EID Emergence** ---------------------------------------- ### **Anthropogenic Drivers** - - - - - - - - - - - ### **Microbial Factors** - - - - **3. Key Historical and Recent EID Examples** --------------------------------------------- ### **Historical Pandemics** - - - - - ### **Notable Modern EIDs** - - - - - - - - - - - **4. Stages of Disease Emergence** ---------------------------------- 1. - 2. - 3. - **5. Disease-Specific Insights** -------------------------------- ### **Malaria** - - - - - ### **Tuberculosis (TB)** - - - - ### **Monkeypox (Mpox)** - - - - - **6. Prevention and Future Preparedness** ----------------------------------------- ### **General Strategies** - - - - - - ### **Key Takeaways** - - Lec 7: Drug Discovery ===================== **1. Early Drug Discoveries** ----------------------------- - - - - - ### **Aspirin: A Case Study** - - - - ### **Paul Ehrlich and Chemotherapy** - - - - ### **Gerhard Domagk and Sulfonamides** - - - - **2. The Modern Drug Discovery Process** ---------------------------------------- ### **Stages** 1. - - 2. - - - 3. - - 4. - - 5. - - - - - - **3. Rational Drug Design** --------------------------- - - - - - ### **Key Concepts** - - - - - - - - - - **4. Emerging Strategies in Drug Discovery** -------------------------------------------- ### **Phenotypic Screening** - - - ### **Target-Based Screening** - - ### **Combined Approach** - - **5. Drug Repurposing** ----------------------- - - - - - - - - - **6. Challenges in Drug Discovery** ----------------------------------- - - - - - ### **Solutions** - - - **7. Case Studies** ------------------- ### **COVID-19 Therapeutics** - - ### **ACE Inhibitors** - -