Principles of Disease

Symbiosis and Its Forms

Symbiosis refers to the close association between two different species living together. There are three main forms:

• Mutualism: Both organisms benefit from the relationship. Example: Escherichia coli in the human gut synthesizes vitamin K for the host and receives nutrients.

• Commensalism: One organism benefits, while the other is neither helped nor harmed. Example: Skin bacteria that live on humans without affecting them.

• Parasitism: One organism (the parasite) benefits at the expense of the other (the host). Example: Pathogenic bacteria causing disease in humans.

Key Epidemiological Terms

• Normal microbiota: Microorganisms that colonize the body without causing disease under normal conditions.

• Endemic disease: Disease constantly present in a population or region.

• Epidemic disease: Disease occurrence in excess of normal expectancy in a community or region.

• Pandemic disease: An epidemic that spreads across countries or continents.

• Sporadic disease: Disease that occurs only occasionally and at irregular intervals.

• Epidemiology: The study of the distribution and determinants of health-related states in populations.

Pathogenicity of Streptococcus pneumoniae

Streptococcus pneumoniae can cause typical pneumonia when it overcomes host defenses, often due to compromised immunity, impaired mucociliary clearance, or pre-existing lung conditions.

Classification of Infectious Diseases

• Infectious disease: Disease caused by pathogenic microorganisms.

• Communicable disease: Disease that can be transmitted from one host to another.

• Contagious disease: Easily spread from person to person.

• Acute disease: Develops rapidly, with severe symptoms but short duration.

• Chronic disease: Develops slowly, with less severe symptoms but persists for a long time.

• Local infection: Confined to a specific area of the body.

• Systemic infection: Spread throughout the body via blood or lymph.

• Primary infection: Initial infection in a healthy individual.

• Secondary infection: Infection occurring after or because of another infection.

Koch’s Postulates

Koch’s Postulates are criteria to establish a causative relationship between a microbe and a disease:

1. The microorganism must be found in all cases of the disease.

2. It must be isolated and grown in pure culture.

3. The cultured microbe must cause disease when introduced into a healthy host.

4. It must be re-isolated from the experimentally infected host.

Exceptions: Some pathogens cannot be cultured in vitro, and some diseases are caused by multiple organisms or only in humans.

Stages of Disease

The five stages of disease are:

1. Incubation period: Time between infection and appearance of symptoms.

2. Prodromal period: Early, mild symptoms.

3. Illness: Most severe symptoms.

4. Decline: Symptoms subside.

5. Convalescence: Recovery and return to normal.

Transmission can occur during incubation, prodromal, and illness stages. Secondary infections are more likely during illness and decline.

Reservoirs, Hosts, and Vectors

• Reservoir: Natural habitat of a pathogen (human, animal, or environment).

• Host: Organism that harbors the pathogen.

• Vector: Living organism (often an arthropod) that transmits pathogens between hosts.

Zoonotic: Diseases transmitted from animals to humans.

Example: Rabies reservoirs include wild mammals; controlling reservoirs is key to preventing transmission.

Modes of Transmission

• Direct transmission: Person-to-person contact (e.g., touching, kissing).

• Indirect transmission: Via fomites (inanimate objects).

• Vehicle transmission: Through air, water, or food.

Nosocomial Infections

Nosocomial (hospital-acquired) infections are acquired in healthcare settings. Three contributing factors:

• Presence of microorganisms in hospital environment

• Compromised host

• Chain of transmission (can be controlled by hygiene and sterilization practices)

Microbial Mechanisms of Pathogenicity

Portals of Entry and Exit

• Portals of entry: Skin, mucous membranes, parenteral route (injection, bites).

• Portals of exit: Respiratory tract, gastrointestinal tract, urogenital tract, skin, blood.

Adhesion and Virulence Factors

• Adhesion factors: Molecules that help pathogens attach to host cells (e.g., fimbriae, adhesins).

• Capsules: Prevent phagocytosis.

• Hyaluronidase and collagenase: Enzymes that degrade host tissues, aiding spread.

• Coagulase: Clots blood to protect bacteria; Kinase: Dissolves clots to spread infection.

Exotoxins vs. Endotoxins

Types and Genetics of Exotoxins

• Types: Cytotoxins, neurotoxins, enterotoxins

• Gene locations: Chromosomal, plasmid, or bacteriophage DNA

Infection vs. Intoxication

• Infection: Pathogen grows and multiplies in the host.

• Intoxication: Disease caused by ingestion of preformed toxins.

Exotoxin-Producing Bacteria

• Clostridium tetani: Produces tetanospasmin (neurotoxin)

• Clostridium botulinum: Produces botulinum toxin (neurotoxin)

• Staphylococcus aureus: Produces enterotoxins and toxic shock syndrome toxin

• Vibrio cholerae: Produces cholera toxin (enterotoxin)

Cytopathic Effects (CPE) of Viruses

• Syncytia formation: Fusion of cells into multinucleated giant cells.

• Inclusion bodies: Aggregates of viral particles or altered host cell components.

• Cell lysis and rounding up: Destruction and morphological changes in host cells.

Interferons and Antigenic Change

• Interferon: Host proteins that inhibit viral replication and activate immune cells.

• Antigenic change: Alteration of surface antigens to evade immune detection.

Co-evolution

Co-evolution refers to the reciprocal evolutionary adaptations between interacting species, such as hosts and pathogens.

Host Defenses

Cells of the Immune System

• Myeloid cells:

  • Mast cells: Release histamine, mediate inflammation.

  • Basophils: Release histamine, involved in allergic responses.

  • Eosinophils: Combat parasites, involved in allergies.

  • Neutrophils: Phagocytose bacteria and fungi.

  • Monocytes/Macrophages: Phagocytosis, antigen presentation.

  • Dendritic cells: Antigen presentation, activate T cells.

• Lymphoid cells:

  • B cells: Produce antibodies.

  • T cells: Cell-mediated immunity (helper and cytotoxic functions).

  • Natural Killer (NK) cells: Destroy infected or abnormal cells.

Innate vs. Adaptive Immunity

• Innate immunity: Non-specific, immediate defense (e.g., skin, phagocytes).

• Adaptive immunity: Specific, slower response involving lymphocytes and memory.

Physical Barriers

• Skin: Physical barrier, secretes antimicrobial substances.

• Mucous membranes: Trap and remove microbes, secrete mucus and enzymes.

Phagocytosis and Evasion

1. Chemotaxis

2. Adherence (PRRs and opsonization enhance this step)

3. Ingestion

4. Phagosome formation

5. Phagolysosome formation

6. Digestion and exocytosis

Certain pathogens (e.g., Leishmania donovani) evade phagocytosis by surviving within phagolysosomes.

Complement System

• Classical pathway: Triggered by antibodies bound to antigens.

• Alternative and lectin pathways: Triggered by microbial surfaces or lectin binding.

• Functions: Opsonization, inflammation, cytolysis.

Other Innate Defenses

• Inflammation: Local response to injury or infection.

• Interferon production: Inhibits viral replication.

• Fever: Elevated body temperature inhibits pathogens and enhances immune response.

Cytokine Storm

Excessive, uncontrolled release of cytokines (e.g., IL-1, IL-6, TNF-α) leading to severe inflammation and tissue damage.

Lymphoid Organs

• Bone marrow: Site of hematopoiesis and B cell maturation.

• Thymus: T cell maturation.

• Lymph nodes: Filter lymph, site of immune activation.

• Spleen: Filters blood, immune surveillance.

• MALT: Mucosa-associated lymphoid tissue, protects mucosal surfaces.

Antibody Structure and Diversity

• Antibodies consist of two heavy chains and two light chains.

• Variable region: Antigen-binding site (Fab region).

• Constant region: Determines antibody class (Fc region is the stem).

Antibody diversity is generated by DNA recombination of variable (V), diversity (D), and joining (J) gene segments.

Classes and Functions of Antibodies

• Agglutination: Clumping of antigens.

• Neutralization: Blocking pathogen binding sites.

• Opsonization: Enhancing phagocytosis.

• Complement fixation: Activating complement system.

• Antibody-dependent cellular cytotoxicity (ADCC): Targeting cells for destruction by NK cells.

Major Histocompatibility Complex (MHC)

T Helper vs. T Cytotoxic Cells

• T helper (Th) cells: CD4+, interact with MHC II, coordinate immune response.

• T cytotoxic (Tc) cells: CD8+, interact with MHC I, kill infected cells.

Immunological Synapse

The immunological synapse is the interface between a T cell and an antigen-presenting cell, involving T cell receptor (TCR) and MHC interaction.

Primary Cell-Mediated (Th1) and Humoral (Th2) Responses

• Th1 response: Involves macrophages, Tc cells, cytokines (e.g., IFN-γ), cell-mediated immunity.

• Th2 response: Involves B cells, clonal selection, antibody production, cytokines (e.g., IL-4), plasma cell maturation, class switching.

Immunological Memory

Memory cells enable a faster and stronger secondary immune response upon re-exposure to the same antigen.

Immune Evasion by Pathogens

• Trypanosoma brucei: Antigenic variation to evade antibodies.

• Influenza virus type A: Antigenic drift and shift to escape immune detection.

Types of Acquired Immunity