Week 2 Flashcards
Describe how pathogens cause disease and how they overcome the innate host defence
Pathogenesis of Infectious Diseases:
Pathogens cause disease through a series of steps known as the pathogenic process. This process involves the following key stages:
1) Entry into Host:
Pathogens enter the host through portals of entry such as the respiratory tract, gastrointestinal tract, or breaks in the skin.
Successful entry is influenced by the pathogen’s ability to overcome physical barriers and evade initial immune responses.
2) Adherence to Host Cells:
Pathogens adhere to host cells using adhesion molecules or surface structures that bind to specific receptors on host cells.
Adherence facilitates colonization and the establishment of infection.
3) Invasion and Colonization:
Pathogens invade host tissues, often aided by virulence factors such as enzymes or toxins.
Once in the host, pathogens colonize and multiply, evading host defenses.
4) Evasion of Immune Responses:
Pathogens have mechanisms to evade or subvert the host’s immune responses.
Strategies include antigenic variation, hiding within host cells, and producing molecules that inhibit immune function.
5) Tissue Damage and Disease Manifestation:
Pathogens cause damage to host tissues directly through toxins, enzymes, or immune responses.
Disease symptoms result from tissue damage, inflammation, and the host’s attempts to eliminate the pathogen.
Evasion of Innate Host Defense:
1) Avoiding Recognition:
Some pathogens have mechanisms to evade recognition by pattern recognition receptors (PRRs) of the innate immune system.
This includes modifying or masking pathogen-associated molecular patterns
(PAMPs).
2) Inhibiting Phagocytosis:
Pathogens may produce substances that inhibit phagocytosis or survive within phagocytic cells.
Capsules, for example, can prevent phagocytic engulfment.
3) Antigenic Variation:
Pathogens may undergo rapid changes in surface antigens, preventing the host immune system from recognizing and mounting an effective response.
4) Immune Evasion Molecules:
Some pathogens produce molecules that interfere with host immune signaling or directly neutralize immune effectors.
Examples include bacterial toxins that disrupt host cell function.
5) Escape from Complement System:
Pathogens may resist complement-mediated destruction through various mechanisms, such as producing complement inhibitors or escaping to areas not reached by complement.
6) Surviving Intracellularly:
Intracellular pathogens can avoid detection and destruction by residing within host cells.
They may manipulate host cell processes or resist the effects of lysosomal enzymes.
7) Inducing Immune Tolerance:
Some pathogens can induce immune tolerance, leading to a subdued or ineffective immune response.
This may involve modulation of regulatory T cells or anti-inflammatory signals.
Describe the fundamentals of vaccination and named examples of successful vaccination campaigns
1) Pathogen Exposure or Components:
Vaccines contain weakened or inactivated forms of pathogens, their toxins, or pathogen components (antigens) that trigger an immune response.
2) Stimulating Immune Response:
The vaccine introduces antigens to the immune system, prompting the production of antibodies and the activation of immune cells, such as T cells.
3) Memory Immune Response:
Memory cells are generated, providing long-lasting immunity. If the person is later exposed to the actual pathogen, the immune system can mount a rapid and effective response.
4) Herd Immunity:
Widespread vaccination within a population can lead to herd immunity, protecting even those who cannot be vaccinated, such as individuals with certain medical conditions.
5) Preventing Disease Spread:
Successful vaccination campaigns contribute to the prevention and control of infectious diseases, reducing the incidence, severity, and transmission of targeted pathogens
Demonstrate an understanding of, and describe the pathogenicity, epidemiology, management and prevention of urinary tract infection, H pylori-associated gastrointestinal disease, viral and bacterial skin and eye infections and viral and bacterial respiratory tract infections
1) Urinary Tract Infection (UTI):
Pathogenicity:
Causative Agents: Mainly bacteria, with Escherichia coli being a common culprit.
Pathogenesis: Bacteria ascend the urethra, reaching the bladder or kidneys, causing inflammation and infection.
Epidemiology:
Risk Factors: Female gender, sexual activity, urinary tract abnormalities, catheter use.
Prevalence: UTIs are common, affecting millions globally.
Management
Antibiotics: Treatment typically involves antibiotics based on urine culture results.
Fluid Intake: Adequate hydration helps flush bacteria from the urinary tract.
prevention
Hygiene Practices: Wiping front to back, urinating after intercourse.
Cranberry Products: Some evidence suggests a preventive role.
2) H. pylori-associated Gastrointestinal Disease:
H. pylori-associated Gastrointestinal Disease:
Pathogenicity:
Causative Agent: Helicobacter pylori, a spiral-shaped bacterium.
Pathogenesis: H. pylori colonizes the stomach lining, leading to gastritis, peptic ulcers, and increasing the risk of gastric cancer.
Epidemiology:
Transmission: Person-to-person, typically in childhood.
Prevalence: High in developing countries; decreases with improved sanitation.
Management
Antibiotics: Eradication therapy with a combination of antibiotics and proton pump inhibitors.
Proton Pump Inhibitors (PPIs): Reduce stomach acid production.
prevention
Hygiene: Reducing person-to-person transmission.
3) Viral and Bacterial Skin and Eye Infections:
Skin Infections:
Pathogenicity: Staphylococcus aureus, Streptococcus pyogenes, and viruses like Herpes simplex.
Management: Antibiotics for bacterial infections, antivirals for viral infections.
Prevention: Proper wound care, hygiene.
Eye infections
Pathogenicity: Bacterial (Staphylococcus, Streptococcus) and viral (adenovirus, herpesvirus).
Management: Antibiotics for bacterial conjunctivitis, antivirals for viral infections.
Prevention: Hand hygiene, avoiding contact with infected individuals.
4) Viral and Bacterial Respiratory Tract Infections:
Respiratory Tract Infections:
Pathogenicity: Influenza virus, respiratory syncytial virus (RSV), Streptococcus pneumoniae, Haemophilus influenzae.
Management: Antivirals for influenza; antibiotics for bacterial infections if indicated.
Prevention: Vaccination (influenza, pneumococcal), hand hygiene, respiratory etiquette.
Demonstrate an understanding of hypersensitivity reactions and the concept of allergy
1) Definition:
Hypersensitivity reactions are exaggerated or inappropriate immune responses to antigens (allergens) that are generally harmless. These reactions can be categorized into four types based on immune mechanisms.
2) Types of Hypersensitivity Reactions:
Type I (Immediate) Hypersensitivity:
Mechanism: Involves IgE antibodies binding to mast cells and basophils, leading to the release of inflammatory mediators like histamine.
Examples: Allergic rhinitis, asthma, anaphylaxis.
Type II (Cytotoxic) Hypersensitivity:
Mechanism: Antibody-mediated destruction of host cells, often involving complement activation.
Examples: Hemolytic transfusion reactions, autoimmune hemolytic anemia.
Type III (Immune Complex) Hypersensitivity:
Mechanism: Formation of immune complexes that deposit in tissues, triggering inflammation.
Examples: Systemic lupus erythematosus, rheumatoid arthritis.
Type IV (Delayed) Hypersensitivity:
Mechanism: Involves sensitized T cells releasing cytokines that attract and activate immune cells, causing tissue damage.
Examples: Contact dermatitis, tuberculin skin test.
3) Concept of Allergy:
Definition: Allergy refers specifically to type I hypersensitivity reactions.
Allergens:
Common Allergens: Pollens, dust mites, pet dander, foods (e.g., nuts, shellfish), insect venom.
Contact Allergens: Certain metals, latex, certain chemicals.
Clinical Manifestations:
Respiratory Allergies: Sneezing, nasal congestion, wheezing, asthma.
Skin Allergies: Hives, eczema, itching.
Anaphylaxis: Severe, life-threatening reaction involving multiple organ systems.
Diagnostic Tools:
Skin Prick Tests: Exposure to allergens results in a wheal-and-flare reaction.
Blood Tests: Measure specific IgE antibodies.
Management:
Avoidance: Identifying and avoiding allergens.
Pharmacotherapy: Antihistamines, corticosteroids for symptom relief.
Immunotherapy (Desensitization): Gradual exposure to increasing doses of allergens to induce tolerance.
Prevention:
Early Introduction of Foods: Introducing common allergenic foods to infants to reduce the risk of food allergies.
Reducing Environmental Exposure: Strategies to minimize exposure to allergens.
4) Key Concepts:
Sensitization: Initial exposure leads to the development of immune memory.
Re-Exposure: Subsequent exposure results in an exaggerated immune response.
Genetic Predisposition: Allergic tendencies often run in families.
Demonstrate an understanding of different formulations for parenteral application with particular focus on the delivery route (IV, IM, SC, infustion) including nano-formulation
1) Intravenous (IV) Formulations:
Standard Formulations: Liquid solutions or emulsions.
Characteristics: Rapid onset of action due to immediate drug availability in the bloodstream.
Examples: Intravenous solutions, such as saline or dextrose, and IV medications in solution form.
2) Intramuscular (IM) Formulations:
Standard Formulations: Solutions, suspensions, or emulsions.
Characteristics: Absorption rate influenced by formulation type; suitable for sustained-release formulations.
Examples: Antibiotics, vaccines, and long-acting medications like depot injections.
3) Subcutaneous (SC) Formulations:
Standard Formulations: Solutions, suspensions, or emulsions.
Characteristics: Slower absorption than IM; suitable for sustained-release formulations.
Examples: Insulin, heparin, and some growth hormones.
4) Infusion Formulations:
Standard Formulations: Intravenous solutions administered over a set period.
Characteristics: Controlled and continuous drug delivery; used for fluids, electrolytes, and medications.
Examples: Chemotherapy infusions, parenteral nutrition, and certain antibiotics.
5) Nano-formulations:
Nanoparticles: Drug particles in the nanometer range, enhancing bioavailability and targeted delivery.
Liposomes: Lipid vesicles carrying drugs, improving drug solubility and stability.
Polymeric Nanoparticles: Polymer-based carriers for sustained release and improved drug delivery.
Characteristics: Increased drug stability, prolonged release, reduced side effects, and targeted delivery.
Applications: Cancer therapy, gene delivery, and treatment of infectious diseases.
Considerations for Formulation Design:
Solubility: Formulations address issues of drug solubility, enhancing absorption and bioavailability.
Stability: Ensuring stability during storage and administration is crucial.
Particle Size: Nano-formulations optimize particle size for improved drug delivery.
Benefits of Nano-formulations:
Targeted Delivery: Nanoparticles can be engineered to target specific cells or tissues.
Enhanced Bioavailability: Improved solubility increases drug absorption.
Reduced Side Effects: Controlled release minimizes systemic exposure.
Prolonged Action: Sustained-release formulations enhance drug duration.
Demonstrate a broad understanding of different types of vaccines and why they are used
1) Live Attenuated Vaccines:
Composition: Weakened, but still live, forms of the pathogen.
Examples: Measles, Mumps, Rubella (MMR), Varicella (chickenpox), Oral Polio Vaccine (OPV).
Advantages: Strong and long-lasting immune response.
Considerations: Unsuitable for immunocompromised individuals; potential for reversion to virulence.
2) Inactivated or Killed Vaccines:
Composition: Pathogens that have been killed or inactivated.
Examples: Inactivated Polio Vaccine (IPV), Hepatitis A, Influenza (injectable), Rabies.
Advantages: Safer for immunocompromised individuals; no risk of reversion to virulence.
Considerations: May require booster shots for sustained immunity.
3) Subunit, Recombinant, or Conjugate Vaccines:
Composition: Contain only specific portions of the pathogen, such as proteins or sugars.
Examples: Human Papillomavirus (HPV), Hepatitis B, Haemophilus influenzae type b (Hib) conjugate vaccine.
Advantages: Reduced risk of adverse reactions; targeted immune response.
Considerations: Often require booster shots for prolonged protection.
4) Messenger RNA (mRNA) Vaccines:
Composition: Use genetic material (mRNA) that encodes pathogen proteins to stimulate an immune response.
Examples: Pfizer-BioNTech and Moderna COVID-19 vaccines.
Advantages: Rapid development; no live virus used; adaptable to emerging pathogens.
Considerations: Storage requirements, new technology with evolving understanding.
5) Viral Vector Vaccines:
Composition: Use a harmless virus (vector) to deliver genetic material encoding pathogen proteins.
Examples: Oxford-AstraZeneca COVID-19 vaccine, Johnson & Johnson COVID-19 vaccine.
Advantages: Efficient immune response; adaptable to various pathogens.
Considerations: Potential pre-existing immunity to the vector.
6)Toxoid Vaccines:
Composition: Inactivated toxins produced by bacteria, rather than the bacteria itself.
Examples: Diphtheria, Tetanus.
Advantages: Prevent diseases caused by bacterial toxins.
Considerations: May require booster shots for sustained immunity.
Why Vaccines are Used:
1) Disease Prevention:
Vaccines protect individuals and populations from infectious diseases, preventing illness, complications, and mortality.
2) Herd Immunity:
Vaccination contributes to herd immunity, reducing the overall spread of pathogens and protecting those who cannot be vaccinated.
3) Public Health Impact:
Vaccines play a pivotal role in public health by reducing the burden of diseases, hospitalizations, and healthcare costs.
4) Eradication and Control:
Vaccines have led to the eradication of smallpox and the control of diseases like polio, demonstrating their effectiveness in public health initiatives.
Describe methods for delivery of drugs to the nose and lung.
1) Nasal Sprays:
Mechanism: Liquid formulations sprayed into the nasal cavity.
Applications: Treat allergic rhinitis, congestion, or deliver medications like nasal decongestants, corticosteroids, or antihistamines.
Advantages: Rapid absorption, localized action, avoids first-pass metabolism.
2) Nasal Drops:
Mechanism: Liquid drops applied directly into the nostrils.
Applications: Common for pediatric use; delivers medications for nasal congestion, infections, or allergies.
3) Nasal Gels and Ointments:
Mechanism: Semi-solid formulations applied to the nasal mucosa.
Applications: Provides prolonged contact time for drugs; useful for dry nasal passages or infections.
4) Nasal Powders:
Mechanism: Powdered formulations inhaled through the nose.
Applications: Can improve drug stability; used for vaccines and antimicrobial agents.
5) Nasal Aerosols:
Mechanism: Fine mist or particles delivered into the nasal cavity.
Applications: Offers controlled and uniform drug delivery; potential for systemic absorption.
Delivery of Drugs to the Lungs:
1) Metered-Dose Inhalers (MDIs):
Mechanism: Pressurized canisters release a precise dose of medication as an aerosol.
Applications: Common for bronchodilators and corticosteroids in asthma and chronic obstructive pulmonary disease (COPD).
2) Dry Powder Inhalers (DPIs):
Mechanism: Administers a dry powder formulation when the patient inhales.
Applications: Used for bronchodilators and anti-inflammatory drugs; no propellant required.
3) Nebulizers:
Mechanism: Converts liquid medication into a fine mist for inhalation.
Applications: Ideal for patients unable to use MDIs or DPIs; common in hospitals for severe respiratory conditions.
4) Spacer Devices:
Mechanism: Attachments for MDIs to enhance drug delivery by reducing the need for precise coordination between inhalation and actuation.
Applications: Improve drug deposition in the lungs; enhance drug delivery to lower airways.
5) Inhalable Powders:
Mechanism: Powdered formulations for inhalation through DPIs.
Applications: Used for various respiratory medications; stable and easy to use.
6) Liposomal Inhalation:
Mechanism: Liposomes (lipid vesicles) containing drugs for inhalation.
Applications: Enhance drug stability, improve lung targeting, and reduce systemic side effects.
7) Aerosolized Antibiotics:
Mechanism: Aerosolized formulations of antibiotics for targeted delivery to the lungs.
Applications: Treat respiratory infections, particularly in cystic fibrosis patients.
Considerations for Inhalation Delivery:
Particle size: Critical for optimal deposition in the respiratory tract.
Patient coordination: Proper inhalation technique is crucial for effective drug delivery.
Device design: Different devices suit various patient populations and drug formulations.
Q1) Discuss the innate immune defences present in a host to prevent microbial infection of the airway
innate= first-line defence, rapidly evoked, non-specific, physical barriers
adaptive= slow activation, specificity, memory
Physical barriers
Mucus and cilia- act as a physical barrier, trapping inhaled particles and pathogens
move both the mucus layer and fluid (beating action)
Epithelial cells- tight junction prevent pathogens
Skin—both chemical and biological: antiseptic sebum and skin flora present for competition
Chemical barriers
Antimicrobial peptides - can directly kill or inhibit the growth of pathogens
Lysozyme (anti-microbial compound) - found in respiratory secretions can break down the cell walls of bacteria
Lymphocytes and antigen-presenting cells
The airway has specialised lymphoid tissue that houses immune cells
types of antigen presenting cells
1) Dendritic cells
Most potent
Particularly in tissues in contact with external environment such as skin, respiratory tract and gut
High capacity to capture antigens
Process them into smaller fragments
Display these fragments on their cell surface
2) Macrophages
Phagocytic immune cells found in various tissues
Engulf and digest pathogens
Process these antigen for presentation to T cells
3) Neutrophils
Most abundant white blood cells in the bloodstream
Engulf and digest pathogens
Release antimicrobial molecules to help eliminate bacteria
4) Natural killer cells
Type of lymphocyte that specialised in killing infected or abnormal cells
Can identify target based on their lack of certain self-recognition
5) Basophils and eosinophils
Play roles in allergic responses and defense against parasites
Release histamine during allergic reactions
Eosinophils are involved in the defense against parasitic infections and can modulate allergic responses
Q2) Describe how pathogenic bacteria have evolved to infect the airway focusing on the concepts of host attachment, nutrient acquisition and immune evasion.
1)Host attachment
Adherence factors
Pathogenic bacteria contan adhesins on their surface
They interact with host cell receptors
Allowing bacteria to attach firmly to the epithelial cells in the airway
Fimbriae and pili
Promote adhesion to host cells
Binding to specific molecules on the host cell surface
2)Nutrient acquisition
Iron acquisition
Pathogens develop various mechanisms to acquire iron from host
Siderophores are molecules that scavenge iron from host proteins
Utilization of host molecules
Bacteria can use host-derived molecules
Mucins and glycoproteins as sources of carbon and energy for growth
3)Immune invasion
Capsules
Made of a polysaccharide layer
Polysaccharide capsule is a critical virulence factor for some bacteria when it comes to survival in the bloodstream
Protection
Capsule acts as a physical barrier
Inhibits the process of phagocytosis where immune cells engulf and destroy invading bacteria
Inhibits the attachment of phagocytic cells to the bacterial surface
Survival in blood
A hostile environment with capsule better equipped to survive
Some capsule mimic host components which prevent the immune system from recognizing it as foreign organisms so don’t raise immune response. Endotoxins help damage the host cell by causing lysis.
Q4) With reference to the relevant NICE guidance, how would you assess the severity of the infection, referring to CURB65?
CURB65= used in hospitals to assess 30- day mortalility risk. 1 point is give to each feature
confusion
urea more than 7mmol/litre
Respiratory rate 30/minute or more
Blood pressure: Low systolic (less than 90mmHg) or diastolic (60mmHg or less)
Age 65 or more
0 or 1: low risk (3% mortality risk)
2: intermediate risk (3% to 15% risk)
3 to 5: high risk (more than 15% mortality risk)
Q5) How would you treat the infection? Give the chemical structure of your therapeutic compound and use this to discuss its mechanism of action and oral availability
Macrocyclic lactone ring-> plays role in bacteriostaic antibiotic
Binds to 23s rRNA of the bacterial 50s ribosomal unit
Hydrogen bonding:
Many oxygen atoms
Forms hydrogen bonds
With specific residues on the ribosimal subunit
Increases stability
Stops bacterial protein synthesis
Inhibits the translocation step (preventing the ribosome from moving along the mRNA)
Thus no bacterial proteins produce
Stops bacteria from multiplying
Q5) How would you treat the infection? Give the chemical structure of your therapeutic compound and use this to discuss its mechanism of action and oral availability
Q7) Discuss what type of vaccine technology would be required for your three vaccinations identified in Q6, with reference to active ingredient and formulation
Describe the immune system responses in the case of a bacterial versus a viral infection.
The answer should explain the complement-mediated lysis, phagocytosis and adaptive immunity versus a cell mediated response via cytotoxic T cells, interferons and viruses (5 marks)
