Principles of Disease, Pathogenicity, and Immunity: Study Notes for Microbiology

Principles of Disease and Epidemiology

Core Definitions

• Pathology: The scientific study of disease, including its causes, development, and effects on the body.

• Etiology: The identification of the specific microbial cause of a disease.

• Pathogenesis: The sequence of events in the development of a disease.

• Infection: The invasion and colonization of the body by pathogenic microorganisms.

• Disease: A condition in which normal body functions are impaired due to infection or other factors.

The Human Microbiome

• Acquisition: The human microbiome is established rapidly after birth, influenced by delivery method.

• Vaginal Delivery: Newborns are colonized by maternal Lactobacillus species.

• C-Section: Newborns are colonized by skin-associated Staphylococcus species.

• Distribution: Microbial populations are shaped by local pH, moisture, and oxygen levels.

• Normal Microbiota: Permanent, beneficial microbes that help prevent disease by outcompeting pathogens.

• Transient Microbiota: Microbes that are present temporarily and do not establish permanent residence.

• Human Microbiome Project: Revealed that bacterial cells in the human body are as numerous as human cells.

Microbial Antagonism (Competitive Exclusion)

• Nutrient Competition: Normal flora consume available nutrients, limiting resources for pathogens.

• pH Alteration: Lactobacillus species produce acid, inhibiting the growth of yeast and other microbes.

• Oxygen Control: Colonic bacteria reduce oxygen levels, favoring anaerobic microbes.

• Bacteriocins: Proteins produced by resident E. coli that kill competing bacteria.

Symbiotic Relationships

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

• Mutualism: Both organisms benefit (e.g., gut bacteria synthesizing vitamins).

• Parasitism: One organism benefits at the expense of the host (e.g., pathogenic bacteria).

• Opportunistic Pathogens: Normal flora that cause disease when host defenses are compromised.

Exceptions to Koch's Postulates

• Unculturable Microbes: Some pathogens (e.g., Treponema pallidum) cannot be grown in artificial media.

• Multiple Pathogens: Some diseases (e.g., nephritis) can be caused by various microbes.

• Human-Only Hosts: Ethical constraints prevent testing certain pathogens in humans (e.g., HIV).

• Variable Manifestations: Some pathogens (e.g., Streptococcus pyogenes) cause different diseases.

Indicators, Scope, and Progression of Disease

• Symptoms: Subjective changes experienced by the patient (e.g., pain, fatigue).

• Signs: Objective, measurable changes observed by clinicians (e.g., fever, rash).

• Syndrome: A specific group of signs and symptoms that characterize a disease.

• Communicable Diseases: Infectious diseases that can be transmitted from person to person.

• Noncommunicable Diseases: Diseases not spread between hosts (e.g., tetanus from environment).

• Herd Immunity: When a large portion of a community is immune, reducing disease spread.

• Susceptibility Factors: Genetics, gender, climate, fatigue, and nutrition influence disease risk.

• Stages of Disease Progression:

  1. Incubation Period

  2. Prodromal Period

  3. Period of Illness

  4. Period of Decline

  5. Period of Convalescence

Reservoirs and Transmission Routes

• Human Reservoirs: Infected individuals, including asymptomatic carriers.

• Zoonotic Reservoirs: Animals that harbor pathogens transmissible to humans.

• Nonliving Reservoirs: Soil and water contaminated with pathogens.

• Direct Contact: Physical transfer via touching, kissing, or sexual contact.

• Indirect Contact: Transmission via fomites (inanimate objects).

• Congenital Transmission: Pathogens crossing the placenta from mother to fetus.

• Droplet Transmission: Short-range (<1 meter) spread via respiratory droplets.

• Vehicle Transmission: Spread via contaminated water, food, or air.

  • Waterborne: e.g., cholera outbreaks from fecally contaminated water.

  • Airborne: Pathogens in droplet nuclei traveling >1 meter.

  • Foodborne: Ingestion of contaminated or undercooked food.

• Vector Transmission:

  • Mechanical: Passive transport on insect bodies (e.g., flies).

  • Biological: Pathogen reproduces within vector (e.g., mosquito-borne malaria).

Healthcare-Associated Infections (HAIs) and MRSA

• Nosocomial Infections: Infections acquired in healthcare settings.

• Drivers: Compromised hosts, transmission chains, and hospital-adapted microbes.

• Mannitol Salt Agar: Selective for Staphylococcus; differentiates species by mannitol fermentation.

• MRSA Strains:

  • USA100: Healthcare-associated, multidrug-resistant.

  • USA300: Community-acquired, highly virulent, produces leukocidins.

• Epidemiology Branches:

  • Descriptive: Case studies and mapping (e.g., John Snow).

  • Analytical: Statistical analysis (e.g., Florence Nightingale).

  • Experimental: Controlled experiments (e.g., Ignaz Semmelweis).

• Surveillance: The CDC monitors and reports morbidity and mortality nationwide.

Microbial Mechanisms of Pathogenicity

Virulence Metrics

• Pathogenicity: The ability of a microorganism to cause disease (qualitative).

• Virulence: The degree of pathogenicity (quantitative measure).

• ID50: Infectious dose required to infect 50% of a population.

• LD50: Lethal dose required to kill 50% of a population.

Host Entry and Adherence

• Portals of Entry: Mucous membranes (respiratory, GI, genitourinary), skin, and parenteral route (punctures).

• Preferred Portal: Many pathogens must enter through a specific route to cause disease.

• Adherence: Microbial adhesins (ligands) bind to host cell receptors, often initiating infection.

• Biofilms: Communities of microbes encased in extracellular polymeric substances (EPS) that resist antibiotics and immune clearance.

Evading Host Defenses

• Glycocalyx Capsules: Prevent phagocytosis by host immune cells.

• Capsulated Pathogens: Streptococcus pneumoniae, Haemophilus influenzae, Bacillus anthracis.

• M Protein: Cell wall protein of Streptococcus pyogenes that resists acid and phagocytosis.

• Opa Proteins: Surface proteins of Neisseria gonorrhoeae aiding in attachment and invasion.

• Mycolic Acid: Waxy lipid in cell walls (e.g., Mycobacterium) that resists digestion.

• Antigenic Variation: Pathogens alter surface proteins to evade immune detection.

• Invasins: Surface proteins that induce host cell membrane ruffling, facilitating entry.

• Intracellular Survival: Mechanisms include actin propulsion, lysosomal escape, and blocking phagolysosome fusion.

• Siderophores: Bacterial proteins that scavenge iron from host proteins (e.g., transferrin).

Exotoxins vs. Endotoxins

Feature	Exotoxins	Endotoxins
Source	Gram-positive & Gram-negative bacteria	Gram-negative bacteria only
Chemical Nature	Proteins, secreted	Lipid A of LPS, released on cell lysis
Toxicity	High (low LD50)	Low (high LD50)
Fever Production	No	Yes (pyrogenic)

Exotoxin Categories and Diagnostics

• A-B Toxins: Two-part toxins; B binds to host cell, A alters cell function (e.g., diphtheria toxin).

• Membrane-Disrupting Toxins: Destroy host cell membranes (e.g., hemolysins, leukocidins).

• Superantigens: Cause excessive immune activation (cytokine storm).

• Genotoxins: Damage host DNA, potentially leading to mutations or cancer.

• LAL Assay: Limulus Amebocyte Lysate test detects endotoxins using horseshoe crab blood clotting.

Non-Bacterial Pathogenicity

• Cytopathic Effects (CPEs): Structural changes in host cells due to viral infection (e.g., inclusion bodies, syncytia).

• Fungal Mycotoxins: Toxic metabolites (e.g., aflatoxins) produced by fungi, some are carcinogenic.

• Protozoa/Helminths: Cause disease by tissue destruction and immune evasion.

• Algal Saxitoxins: Neurotoxins from algae causing paralytic shellfish poisoning during red tides.

The Human Immune System

Innate vs. Adaptive Immunity

• Innate Immunity: Non-specific, rapid defense present at birth (e.g., skin, phagocytes).

• Adaptive Immunity: Specific, slower response with memory (e.g., antibodies, T cells).

• Primary Lymphoid Organs: Sites of lymphocyte maturation (bone marrow, thymus).

• Secondary Lymphoid Organs: Sites where immune responses are initiated (lymph nodes, spleen, Peyer's patches).

First and Second Line Defenses

• Physical Barriers: Skin (epidermis), mucous membranes trap and remove microbes.

• Chemical Barriers: Acidic skin pH, sebum, lysozyme in secretions.

• Pattern Recognition: Toll-Like Receptors (TLRs) detect Pathogen-Associated Molecular Patterns (PAMPs).

• Phagocytosis Steps:

  1. Chemotaxis

  2. Adherence

  3. Ingestion

  4. Digestion

  5. Elimination

• Phagocyte Types: Free (circulating) and fixed (tissue-resident) phagocytes.

• Inflammatory Response: Sequence: vasodilation, leukocytosis, margination, diapedesis, chemotaxis, tissue repair.

• Cardinal Signs of Inflammation: Redness, swelling, heat, pain, loss of function.

• Tissue Repair: Parenchyma restores function; stroma forms scar tissue.

• Natural Killer (NK) Cells: Destroy abnormal cells lacking MHC-I via perforins and granzymes.

• Interferons: Alpha/beta interferons induce antiviral states; gamma interferon activates macrophages.

• Complement System: Protein cascade leading to opsonization, inflammation, and cytolysis via Membrane Attack Complex (MAC). $\text{C3} \xrightarrow{\text{activation}} \text{C3a} + \text{C3b}$

• Fever: Systemic increase in body temperature triggered by pyrogens.

Adaptive Immunity and Antibodies

• Humoral Immunity: B cells produce antibodies targeting extracellular pathogens.

• Cellular Immunity: T cells target and destroy infected or abnormal cells.

• Cytokines: Signaling molecules (interleukins, chemokines, interferons, hematopoietic factors) coordinating immune responses.

• Lymphocyte Development: Origin in bone marrow, maturation (B cells in marrow, T cells in thymus), seeding in lymphoid organs, activation by antigen, clonal expansion.

• Antibody Structure: Y-shaped molecules with two heavy and two light chains, variable (antigen-binding) and constant regions. $\text{Antibody} = 2 \times \text{Heavy Chains} + 2 \times \text{Light Chains}$

• Antibody Classes:

  • IgG: Most abundant, crosses placenta.

  • IgM: First responder, pentameric structure.

  • IgA: Dimer, found in secretions (mucus, saliva).

  • IgE: Binds mast cells, involved in allergies.

  • IgD: B cell receptor, function not fully understood.

• Antibody Actions: Neutralization, agglutination, opsonization, complement activation.

Immunity Classification and MHC Systems

Type	How Acquired	Example
Natural Active	Infection by pathogen	Recovery from measles
Natural Passive	Maternal antibody transfer	Placental IgG
Artificial Active	Vaccination	Flu shot
Artificial Passive	Injection of antibodies	Anti-venom, IVIG

• Class I MHC: Present on all nucleated cells; present antigens to CD8+ cytotoxic T cells.

• Class II MHC: Present on antigen-presenting cells (APCs); present antigens to CD4+ helper T cells.

• Helper CD4+ T Cells: Activate both humoral and cellular immune responses.

• Cytotoxic CD8+ T Cells: Induce apoptosis in infected or abnormal cells via perforins and granzymes.