Microbiology Exam 2 Study Guide: Principles of Disease, Immunity, and Antimicrobial Drugs

Principles of Disease and Epidemiology

Normal Microbiota

Normal microbiota are permanent residents of the human body that do not cause disease under normal conditions. They play essential roles in health and disease prevention.

• Microbial antagonism: Normal microbiota compete with pathogens for resources, preventing their colonization.

• Consume waste/dead cells: Help maintain tissue health.

• Produce beneficial products: Such as vitamins (e.g., Escherichia coli synthesizes vitamin K).

Examples: Staphylococcus (skin, nose, throat), Corynebacterium (eyes), Lactobacillus (intestine, mouth, reproductive system), Escherichia coli (intestine).

Symbiosis: Types and Roles

Symbiosis describes close relationships between two species:

• Commensalism: One benefits, other unaffected (e.g., skin bacteria).

• Mutualism: Both benefit (e.g., E. coli produces vitamin K).

• Parasitism: One benefits at the other's expense.

Opportunistic Pathogens

Microbes that normally do not cause disease but can under certain conditions (e.g., immune suppression, changes in microbiota, introduction to unusual sites).

Etiology and Koch’s Postulates

Etiology: Study of disease causes. Robert Koch demonstrated microbes cause disease (anthrax).

1. Pathogen present in every case.

2. Isolate and grow in pure culture.

3. Introduce to healthy host; same disease develops.

4. Re-isolate pathogen from new host.

Limitations: Not all diseases fit (e.g., viral diseases, unculturable pathogens, ethical issues).

Signs vs. Symptoms

• Signs: Objective, measurable (fever, rash).

• Symptoms: Subjective, felt by patient (pain, nausea).

Types of Disease

• Communicable: Spread person-to-person (e.g., influenza).

• Noncommunicable: Not spread person-to-person (e.g., diabetes).

Disease Frequency Terms

• Endemic: Constantly present.

• Sporadic: Occasional.

• Epidemic: High frequency in area.

• Pandemic: High frequency worldwide.

Acute, Chronic, and Latent Disease

• Acute: Rapid onset (e.g., influenza).

• Chronic: Long-lasting (e.g., tuberculosis).

• Latent: Dormant, then reactivates (e.g., herpes).

Reservoirs and Transmission

• Reservoirs: Human (TB), animal (rabies), nonliving (soil, water).

• Transmission: Direct contact, indirect (fomite), droplet, vehicle (water, food), vector (mechanical, biological).

Nosocomial Infections

Acquired in hospitals; prevented by hygiene, sterilization, PPE, aseptic technique.

Innate Immunity: Nonspecific Defenses

Immunity and Types

Immunity: Ability to resist disease. Divided into innate (nonspecific, present from birth) and adaptive (specific, memory).

• Innate: Skin, mucous membranes, phagocytosis, inflammation, fever, complement, interferon, iron-binding proteins, antimicrobial peptides.

• Adaptive: T cells, B cells, antibodies.

Activation of Innate Defenses

Some defenses are always present; others activated by PAMPs (Pathogen-Associated Molecular Patterns) binding to TLRs (Toll-like Receptors) on host cells, triggering cytokine production.

First Line of Defense

• Skin: Physical (epidermis, keratin), chemical (sebum, sweat, lysozyme).

• Mucous membranes: Epithelial cells, mucus, cilia, secretions.

• Lacrimal apparatus: Tears wash, contain lysozyme.

• Movement: Coughing, sneezing, urination, defecation.

• Normal microbiota: Compete with pathogens.

Second Line of Defense

• Leukocytes: Neutrophils, macrophages, dendritic cells, eosinophils, basophils, NK cells.

• Phagocytosis: Engulf and destroy microbes.

• Lymphatic system: Lymph, vessels, nodes, spleen, thymus, tonsils, bone marrow.

• Inflammation: Redness, heat, swelling, pain; acute vs. chronic.

• Fever: Intensifies defenses, inhibits microbes.

• Complement: Proteins causing cytolysis, opsonization, inflammation.

• Interferons: Antiviral proteins.

• Iron-binding proteins: Starve bacteria.

• Antimicrobial peptides: Destroy microbes.

Phagocytosis Steps

1. Chemotaxis

2. Adherence (opsonization enhances)

3. Ingestion (pseudopods, phagosome)

4. Phagolysosome formation

5. Digestion (killing)

6. Exocytosis

Inflammation Steps

1. Tissue injury/infection

2. Release of chemicals (histamine, leukotrienes)

3. Vasodilation, increased blood flow

4. Leukocyte migration (diapedesis)

5. Phagocyte action

6. Tissue repair

Adaptive Immunity: Specific Defenses

Recognition and Antigens

Adaptive immunity recognizes pathogens by specific antigens. B and T cells have unique receptors for antigens. Antigens are foreign substances that trigger immune responses.

• Exogenous antigens: Enter from outside (bacteria, viruses).

• Endogenous antigens: Produced by infected/cancer cells.

• Autoantigens: Normal proteins; recognized in autoimmune disease.

MHC proteins: Present antigens on cell surfaces. MHC I (all nucleated cells, endogenous), MHC II (APCs, exogenous).

Modes of Adaptive Immunity

• Humoral: B cells, antibodies, extracellular pathogens.

• Cell-mediated: T cells, intracellular pathogens, infected cells.

Antibodies: Structure and Function

Antibodies (immunoglobulins) are proteins produced by B cells. They have two identical antigen-binding sites (valence), usually bivalent (monomer: two light, two heavy chains, Y-shaped).

• Neutralization: Block pathogen/toxin attachment.

• Opsonization: Coat pathogens for phagocytosis.

• Agglutination: Clump pathogens for removal.

• Activation of complement: Trigger complement pathway.

• ADCC: Antibody-dependent cellular cytotoxicity (NK cells, eosinophils destroy infected cells).

B Cells and Antibody Production

• Develop in bone marrow, mature there, circulate in blood/lymph.

• Produce antibodies after activation by antigen and T helper cell cytokines.

• Clonal expansion: Plasma cells (antibody production), memory B cells.

T Cells: Types and Activation

• T Helper (CD4+): Coordinate immune response, activate B cells, cytotoxic T cells, NK cells, eosinophils.

• T Cytotoxic (CD8+): Kill infected cells.

• T Regulatory: Prevent autoimmunity.

Immunological Memory

Memory B and T cells respond rapidly to repeat exposure, often preventing disease symptoms.

Types of Adaptive Immunity

• Naturally Acquired Active: Infection, memory cells produced.

• Naturally Acquired Passive: Maternal antibodies, no memory.

• Artificially Acquired Active: Vaccination, memory cells produced.

• Artificially Acquired Passive: Injection of antibodies (antisera), immediate protection, no memory.

Practical Applications of Immunology & Antimicrobial Drugs

Vaccines and Antisera

• Vaccine: Suspension of pathogens/antigens to induce adaptive immunity and memory.

• Antisera: Ready-made antibodies for immediate passive immunity; used for rapid diseases (rabies, tetanus, antivenom).

Antimicrobial Drugs and Selective Toxicity

• Antimicrobial drugs: Chemicals that kill/interfere with pathogens, little harm to host.

• Selectivity: Target features not present in host (cell wall, ribosome differences, membrane components, nucleic acid synthesis, essential metabolites).

Spectrum of Activity

• Broad-spectrum: Wide variety of pathogens (e.g., tetracycline).

• Narrow-spectrum: Few pathogens (e.g., ketaconzole).

Mechanisms of Antibiotic Action

• Inhibition of cell wall synthesis

• Inhibition of protein synthesis

• Injury to plasma membrane

• Inhibition of nucleic acid synthesis

• Inhibition of essential metabolite synthesis

Drug Resistance

• Mutation: Random DNA changes (antigenic drift in viruses).

• Acquisition of new DNA: Horizontal gene transfer (transformation, conjugation, transduction).

• Mechanisms: Block drug entry, drug inactivation, change target molecule, efflux pumps.

Bacterial Conjugation and Viral Antigenic Shift

• Conjugation: Transfer of plasmids (often carrying resistance genes) via pilus.

• Antigenic shift: Mixing of viral genes from two strains, producing new resistant strains (e.g., influenza).

Practice Problems and Applications

• First line of defense: Sebum, normal microbiota, saliva, tears.

• Phagocytosis: Neutrophils leave bloodstream to attack pathogens.

• NK cells: Kill infected/damaged host cells.

• Eosinophils: Kill parasitic worms, phagocytosis.

• PAMPs: Chitin, bacterial DNA, viral spike proteins.

• Second line of defense: Macrophages, inflammation.

• Phagocytosis steps: Chemotaxis → Adherence → Ingestion → Digestion.

• Antimicrobial peptides: Short chains, important in innate immunity.

• Innate immunity against viruses: Interferon.

• Adaptive immunity: Antibodies, B cell receptors, T cell receptors.

• Antigen types: Autoantigens (healthy cells), endogenous (infected cells), exogenous (microbes).

• Antibody structure: Two identical light and heavy chains (monomer).

• IgM: Pentamer, IgA: Dimer, IgG: Monomer.

• Antibody functions: Opsonization, complement activation.

• Artificially acquired passive immunity: Injection of antibodies.

• COVID-19 vaccines: Recombinant (J&J), nucleic acid (Moderna/Pfizer), subunit (Novavax).

• Antimicrobial drugs vs. disinfectants: Selective toxicity is key difference.