Principles of Disease & Epidemiology

Key Definitions

• Pathology: Study of disease.

• Etiology: Cause of a disease.

• Pathogenesis: Development of disease.

• Infection: Invasion or colonization of the body by pathogens.

• Disease: Abnormal state in which the body is not performing normal functions.

• Epidemiology: Study of where and when diseases occur and how they spread in populations.

• Morbidity rate: Number of people affected relative to total population in a given time period.

• Mortality rate: Number of deaths from a disease relative to the population in a given time.

Symbiotic Relationships

Koch's Postulates

• The same pathogen must be present in every case of the disease.

• The pathogen must be isolated from the diseased host and grown in pure culture.

• The pathogen from the pure culture must cause the disease when inoculated into a healthy, susceptible lab animal.

• The pathogen must be isolated from the inoculated animal and shown to be the original organism.

Key point: Koch's postulates establish the etiology of infectious disease, which is essential for treatment and prevention.

Communicable vs. Noncommunicable Diseases

• Communicable disease: Can be spread from one host to another (directly or indirectly).

• Contagious disease: Communicable disease that is easily spread (e.g., influenza).

• Noncommunicable disease: Not spread from host to host; caused by opportunistic pathogens or environmental sources (e.g., tetanus from soil).

Frequency of Disease Occurrence

Incidence vs. Prevalence

• Incidence: Number of new cases in a given time period.

• Prevalence: All cases (old + new) at a specific point in time.

Severity/Duration of Disease

Predisposing Factors

• Gender

• Inherited traits (e.g., sickle cell gene)

• Climate and weather

• Lack of vaccination

• Fatigue

• Age

• Lifestyle and nutrition

• Chemotherapy

Stages of Disease

Reservoirs and Transmission

• Human reservoirs: Carriers may have inapparent infections or latent diseases.

• Animal reservoirs (zoonoses): Diseases transmitted from animals to humans (e.g., rabies, Lyme disease, West Nile).

• Nonliving reservoirs: Soil and water.

Vectors

Modes of Transmission

Healthcare-Associated Infections (HAIs)

• Also called nosocomial infections – acquired while receiving treatment in a healthcare facility.

• Require three factors: microorganisms in the healthcare environment, compromised host, and chain of transmission.

Epidemiology

• CDC collects and analyzes US epidemiological information; publishes the Morbidity and Mortality Weekly Report (MMWR).

• Emerging infectious diseases: new, increasing in incidence, or showing potential to increase – most are zoonotic, viral, and vector-borne.

Microbial Mechanisms of Pathogenicity

Key Terms

• Pathogenicity: Ability of a microbe to cause disease.

• Virulence: Degree of pathogenicity; how severe or damaging.

• Virulence factors: Structures or products that allow a pathogen to cause infection.

• ID50: Infectious dose for 50% of the test population.

• LD50: Lethal dose that kills 50% of the test population.

• Adhesin (ligand): Surface molecule on pathogen that binds to host cell receptor.

Portals of Entry

• Mucous membranes: Respiratory, GI, genitourinary tracts, conjunctiva (most common entry).

• Skin: Requires a break or wound; few pathogens penetrate intact skin.

• Parenteral route: Deposited directly into tissues via puncture, bite, surgery, or injection.

• During pregnancy/birth: Mother to fetus (e.g., HIV, rubella).

Note: The greatest number of pathogens enter through the respiratory system.

Microbial Adherence Mechanisms

• Adhesion requires a lock-and-key match: adhesin (ligand) on pathogen binds to receptor on host cell surface.

• Structures used for adhesion include fimbriae (pili), capsules, and viral spikes.

Capsules & Cell Wall Components

• Capsules: Prevent phagocytosis (e.g., Streptococcus pneumoniae).

• M protein: (Streptococcus pyogenes) resists phagocytosis.

• Mycolic acid: (Mycobacterium tuberculosis) resists digestion inside phagocytes.

• Gram-negative outer membrane: Protects from lysozyme and complement.

Exoenzymes and Their Effects

Mechanisms to Avoid Phagocytosis

• Capsule formation

• Antigenic variation (e.g., Neisseria gonorrhoeae, Influenza)

• Intracellular survival (e.g., Mycobacterium tuberculosis, Listeria, Legionella)

• Invasins: induce host cell membrane ruffling (e.g., Salmonella)

Direct Damage by Pathogens

• Disrupt host cell function

• Use host cell nutrients

• Produce toxic waste products

• Multiply inside host cells causing lysis

• Siderophores: steal iron from host proteins

Exotoxins vs. Endotoxins

Types of Exotoxins

Cytopathic Effects (CPE) of Viruses

• Halts normal cell metabolism

• Inclusion bodies (e.g., Negri bodies in rabies)

• Syncytium formation (e.g., HIV, measles)

• Induces chromosomal and antigenic changes

• Loss of contact inhibition (may lead to cancer)

Innate Immunity: Nonspecific Defenses

Innate vs. Adaptive Immunity

PAMPs and PRRs

• PAMPs: Pathogen-Associated Molecular Patterns (e.g., peptidoglycan, LPS, dsRNA)

• PRRs: Pattern Recognition Receptors on phagocytes, dendritic cells, endothelial cells

• TLRs: Toll-Like Receptors, a type of PRR that triggers immune activation

First Line of Defense – Physical & Chemical Barriers

• Physical barriers: Skin (keratinized), hair follicles, mucous membranes, cilia, normal microbiota

• Chemical barriers: Sebum, lactic acid, lysozyme (tears, saliva), stomach acid, digestive enzymes, acidic vaginal pH, antimicrobial chemicals in semen

Second Line of Defense – Internal Defenses

• Phagocytic cells: Survey tissues, ingest and destroy microbes

• Steps of phagocytosis:

  1. Chemotaxis

  2. Adherence

  3. Ingestion

  4. Phagolysosome formation

  5. Digestion

  6. Discharge

• Natural Killer (NK) cells: Kill virus-infected and cancer cells by releasing perforin and granzymes

Inflammatory Response

• Non-specific local response to tissue damage or pathogen entry

• Cardinal signs: Rubor (redness), Calor (heat), Tumor (swelling), Dolor (pain), Loss of function

• Steps: Injury/Immediate → Vascular Reactions → Edema/Pus Formation → Resolution/Scar Formation

Fever

• Systemic response triggered by pyrogens (e.g., LPS)

• Benefits: Inhibits microbe multiplication, decreases iron availability, increases metabolism and phagocytosis

Complement System

• Over 30 proteins in plasma; activated in a cascade

• Outcomes: Cell lysis (MAC), opsonization, inflammation

Other Antimicrobial Substances

Adaptive Immunity: Specific Defenses

Types of T Cells & Their Roles

MHC I vs. MHC II

Cell-Mediated Immunity (CMI)

• Carried out by cytotoxic T cells (TC cells)

• Targets: virus-infected cells, cancer cells, transplanted cells

• Mechanism: TC cell binds via CD8 + MHC I + antigen, releases perforin and granzymes → apoptosis

Antibody-Mediated (Humoral) Immunity

• Carried out by B cells → plasma cells secrete antibodies

• Most B cell activation requires Helper T2 (TH2) cells

• B cells have MHC II on their surface

• Memory B cells enable rapid secondary response

Antibody (Immunoglobulin) Structure

• Y-shaped protein; 2 heavy + 2 light chains

• FAb regions: variable, antigen-binding

• Fc region: constant, binds immune cells, triggers complement

Classes of Immunoglobulins

Primary vs. Secondary Immune Response

Mechanisms of Antibody Action

• Opsonization: Antibodies coat microbe, enhancing phagocytosis

• Agglutination: Cross-link antigens into clumps

• Neutralization: Block surface receptors on viruses/toxins

• Antitoxin: Neutralizes bacterial exotoxins

• Complement activation: Antibody-antigen complex triggers complement cascade

Types of Adaptive Immunity

Active vs. Passive Immunity

Vaccines

• Antigen or antigen mixture used to induce artificial active immunity

• Provokes primary response; memory cells formed

• Herd immunity: immunity in most of the population limits spread

Applications of Immunology

Biochemical Tests

• Based on enzyme-mediated metabolic reactions

• Physiological reactions reveal enzyme systems; visualized by color change

Serology

• In vitro diagnostic testing of serum

• Detects, identifies, and quantifies antibodies or antigens

• Principle: unknown antibody detected using known antigen, or vice versa

Agglutination and Precipitation

Western Blot

• Proteins separated by gel electrophoresis, detected by antibodies

• Used for HIV verification

Neutralization Reactions

• Viral hemagglutination: viruses agglutinate RBCs

• Hemagglutination inhibition: patient serum neutralizes virus, preventing agglutination

Molecular/Genotypic Methods

• PCR: Amplifies DNA/RNA; highly sensitive

• Hybridization: Probes bind specific sequences for identification

Vaccine Types

• Adjuvants: Chemical additives to improve vaccine effectiveness (e.g., alums, monophosphoryl lipid A)

Immune Disorders

Hypersensitivity / Immunopathology

• Immunopathology: Study of disease states from overreactivity (allergy, autoimmunity) or underreactivity (immunodeficiency)

The Four Types of Hypersensitivity

Type I – Anaphylactic (IgE-Mediated Immediate)

• Sensitization: Allergen exposure → IgE produced → binds mast cells

• Provocation: Allergen re-exposure → mast cell degranulation → histamine, leukotrienes, prostaglandins released

• Effects: Vasodilation, smooth muscle contraction, increased mucus, skin manifestations

• Atopic diseases: Hay fever, asthma, eczema, food/drug allergies

• Systemic anaphylaxis: Rapid, life-threatening; triggers include bee venom, antibiotics

• Treatment: Avoidance, steroids, monoclonal antibodies, cromolyn, antihistamines, desensitization

Type II – Cytotoxic (IgG & IgM)

• Antibodies bind cell surface antigens → complement activation → cell lysis

• Transfusion reactions: Wrong blood type → hemolysis, shock, kidney failure

• Hemolytic disease of the newborn: Rh- mother, Rh+ fetus; prevented by RhoGAM

Type III – Immune Complex

• Antibody + excess soluble antigen → large complexes lodge in tissues → complement activation → tissue damage

• Examples: Serum sickness, Arthus reaction, SLE, rheumatoid arthritis

Type IV – Delayed/Cell-Mediated (T Cells)

• T cells respond to antigens on self or transplanted tissues

• Symptoms arise 24–48 hours after exposure

• Examples: Contact dermatitis, TB skin test, graft rejection, some chronic diseases

Autoimmunity

• Immune system attacks self-antigens (autoantibodies or T cells)

• Systemic (multiple organs) or organ-specific

Immunodeficiency Diseases

Primary (Congenital)

Secondary (Acquired)

• Caused by infection, metabolic disease, chemotherapy, radiation

• AIDS: HIV infects T helper cells, monocytes, macrophages, APCs; depletion of T helper cells impairs immune responses, leading to cancers and opportunistic infections

Additional info: This guide covers core concepts from BIO 150 Exam 3, including disease principles, epidemiology, mechanisms of pathogenicity, innate and adaptive immunity, immunological applications, and immune disorders. It is suitable for exam preparation and review in a college-level microbiology course.