Immunology Quiz: Transmission and Immune Response

Mechanisms of Bacterial Pathogenesis

• Bacteria cause disease through infection, which involves bacterial multiplication.
• Not all infections lead to disease.
• Infection, without disease, can be asymptomatic.
• A short-term relationship between microorganisms and the host can exist, where microbes are eliminated after infection.
• Pathogenesis involves the organism's ability to cause disease.

Microbes-Host Relationship

• Saprophytes are microbes that live in soil and on dead organic matter.
• Commensal bacteria are harmless microbes that live on the host without causing injury.
• Pathogenic bacteria can cause disease.
• Strict/Primary pathogens cause disease in healthy persons.
• Opportunistic pathogens take advantage of pre-existing conditions to cause disease.
• Examples of sites where bacteria reside include the nose, mouth/throat, stomach, gut, vagina, and skin.

Mechanisms of Bacterial Pathogenesis

• Infection is the growth and multiplication of bacteria in/on the body with or without disease.
• Disease results from tissue or organ damage due to the infection.
• Endogenous infections arise from bacteria already within the body (commensal members of normal flora moving to a different site).
• Exogenous infections arise from bacteria that are transmitted from another source/external environment.

Infection vs. Infectious Disease

• Infection is the growth and multiplication of bacteria in the body.
• Infectious disease arises from damage caused by pathogens and the immune response to the infection (immunopathogenesis).
• The immune system has mechanisms to effectively eliminate pathogens that can overwhelm it, and cause damage leading to disease.

Exogenous Infections

• Sources include patients (transmission from active disease to healthy people).
• Infected animals (zoonoses).
• Soil (saprophytic microbes).
• Carriers (individuals harboring pathogens without symptoms but transmitting the disease).
• Modes: Ingestion (food/water), Inhalation (respiratory tract), Trauma, Direct contact (skin-to-skin), Sexual transmission, Blood-borne transmission, Vector-borne transmission, Vertical (mother-to-child) transmission.

Defence Mechanisms Against Infection

• Barriers to invasion (skin, mucous membranes, stomach acid, lysozyme in tears), and physical actions like coughing, sneezing, vomiting, diarrhoea and flushing of the urinary tract prevent pathogen entry.
• Innate immune response (local response) employs phagocytes (macrophages, neutrophils, NK cells), complement system, AMPs (antimicrobial peptides), inflammatory response, and fever.
• Adaptive immune response responds to specific pathogens via antibody-mediated and cell-mediated immune responses resulting in targeted destruction of pathogens.

Soluble Defence Mediators

• Lysozyme: Breaks down bacterial peptidoglycans. (Tears, saliva, nasal secretions, lysosomal granules.)
• Lactoferrin/transferrin: Competes with microbes for iron. (Specific granules of PMNs)
• Lactoperoxidase: Inhibits many microorganisms. (Milk and saliva)
• β-Lysin: Effective against Gram-positive bacteria. (Thrombocytes, normal serum.)
• Chemotactic factors: Promote migration of phagocytic cells. (Complement and chemokines)
• Properdin: Activates complement in absence of antibody. (Plasma)
• Lectins: Promote microbial phagocytosis. (Plasma)
• Cationic peptides: Disrupt microbial membranes, block cell transport. (Polymorphonuclear granules, epithelial cells)

Lactoferrin

• Host cells secrete lactoferrin that bind iron and compete with microorganisms, preventing pathogen acquisition of iron and aiding in sequestration.
• Pathogens can respond by "stealing" iron or producing stealth siderophores that are resistant to neutralization measures.

Mother-to-Child Transmission

• Infection can be transmitted across the placenta, during delivery, or through breastfeeding.
• Different bacteria and viruses can be transmitted through these methods to cause disease.

Pathogenic Infection

• Microbes cause disease by killing host cells directly or by releasing toxins.
• Exposure, adhesion, invasion, colonization, toxins, tissue damage lead to disease state.

Microbial Toxins

• Exotoxins are secreted proteins that may cause characteristic diseases (diphtheria, tetanus, cholera).
• Examples of Exotoxins classes are cytolytic, A-B toxins, and superantigens.
• Endotoxins are components of outer bacterial layers, released from dying cells of gram-negative bacteria and is a potent activator of inflammatory reactions (ex. LPS).

Exotoxins (Specific Types)

• Pore-forming toxins (PFTs). Water-soluble molecules causing oligomerization and generating pores in the host cell membrane leading to cell death.
• Membrane-disrupting enzymes. Proteins that degrade sphingomyelin and phospholipids of the cell membrane leading to cell death.
• A-B toxins. Have a binding subunit (B) and an active subunit (A) which cause disease through different mechanisms (e.g., cholera toxin).
• Superantigens. Trigger excessive and ineffective activation of T-cells and release of cytokines, leading to toxic shock syndrome.

Endotoxins

• Part of outer cell wall of Gram-negative bacteria and released when the bacterial cell wall breaks.

• Examples are Lipid A and O antigens.

• At low concentrations, stimulate protective responses (e.g., increases in cytokines, antibody synthesis, inflammatory response).

• At high concentrations, cause shock and death through disseminated intravascular coagulation, hypotension and hypoglycemia.

Phagocytes and Inflammation

• Macrophages use surface receptors, initiate phagocytosis, leading to lysis, release of cytokines and the induction of leukocyte infiltration (inflammation) into affected sites.

Inflammation

• Localized physical condition involving redness, swelling, heat, pain, in response to injury or infection.
• Is a defense mechanism, where the immune system recognizes damaged cells, irritants, and pathogens to begin the healing process.
• The four cardinal signs are: redness, heat, pain, swelling.