4th exam part 2

Host Pathogen Interactions - Innate Immune Systems

• Terminology
  • Susceptibility: Lack of resistance to a disease
  • Resistance: Ability to ward off disease
  • Non-specific resistance: Defenses against any pathogen
  • Specific resistance: Immunity, resistance to a specific pathogen

Mechanisms of Pathogenicity

• Pathogenicity is the ability to cause disease
• Number of invading microbes influences severity
• Portals of entry: Mucous membranes (respiratory, gastrointestinal, genitourinary tracts, conjunctiva, skin), Parenteral route
• Penetration or evasion of host defenses: Capsules, cell wall components, enzymes, siderophores, antigenic variation, cytoskeleton
• Damage to host cells/cytopathic effects: Direct damage, toxins (exotoxins, endotoxins), lysogenic conversion
• Portals of exit: Generally the same as portals of entry

Host Defense Mechanisms

• Defense mechanisms are categorized into innate and adaptive (specific) immunity
• Non-specific immunity protects against most disease agents, and its function can be influenced by stress, age, and diet
• Specific immunity protects against a particular pathogen

Host Defenses

• Nonspecific Resistance

  • First line of defense: Intact skin, mucous membranes and secretions, normal microbiota
  • Second line of defense: Phagocytic white blood cells, inflammation, fever, antimicrobial substances (complement)

• Specific Resistance

  • Third line of defense: Specialized lymphocytes (B cells, T cells), antibodies

• Receptors for Pathogen Recognition

  • Toll-like receptors (TLRs)
  • Complement
  • Pattern recognition

• Specialized cells

  • Antigen or shape recognition
  • "Learned" or adaptive
  • Intercellular - Humoral
  • Intracellular - Cellular

Immune System Flow

• Preformed: Barriers, antimicrobials, microbiota
• Induced: ... (diagram shows process)

First Line of Defense

• Physical barriers: Skin (most visible barrier), mucous membranes (digestive, respiratory, genitourinary tracts)
• Chemical barriers:
  • Lysozyme in tears and other secretions
  • Acid in stomach (low pH)
  • Antimicrobial factors in saliva (lysozyme, peroxidase, lactoferrin)
  • Skin-physical barrier, fatty acids, sweat, normal flora
  • Rapid pH change from stomach to upper intestine
  • Flushing of the urinary tract
  • Normal flora of the vagina

Skin

• Provides the most difficult barrier to penetrate
• Composed of two main layers: Dermis and epidermis
• Dermis: Contains tightly woven fibrous connective tissues, making it tough
• Epidermis: Composed of many layers of epithelial cells, becoming increasingly flat as they reach the surface, outermost sheets embedded with keratin, making it water repellent, outer layers slough off, taking microbes with them.

Other Factors

• Mucous membranes and secretions: Ciliary escalator (traps microbes in mucus transported away from the lungs), lacrimal apparatus (washes eye), saliva (washes microbes off), urine (flows out), vaginal secretions (flow out), defecation, vomiting

Normal Microbiota and the Host

• Microbial antagonism: Competition between microbes
• Normal microbiota protect the host by: Occupying niches that pathogens might occupy, producing acids, producing bacteriocins
• Probiotics: Live microbes applied to or ingested into the body, intended to exert a beneficial effect

Normal Microbiota and the Host (continued)

• Transient microbiota: Present for days, weeks, or months
• Normal microbiota: Permanently colonize the host
• Symbiosis: Relationship between normal microbiota and the host

Symbiosis

• Commensalism: One organism benefits, the other is unaffected
• Mutualism: Both organisms benefit
• Parasitism: One organism benefits at the expense of the other
  • Some normal microbiota are opportunistic pathogens

Infection

• A condition in which pathogenic microbes penetrate host defenses, enter tissues, and multiply

Disease

• Any deviation from health, disruption of a tissue or organ caused by microbes or their products

Who are these guys? (Pathogens)

• Includes bacteria, fungi, protozoa, viruses, and arthropods
• Mostly in contact with the outside environment (large intestine has the highest numbers of bacteria)
• Internal organs and tissues & fluids are microbe-free
  • Presence of microbes indicates infection

Physiological Barriers (Second Line Defenses)

• Blood elements (PAMP recognition)
  • Phagocytes
  • Complement proteins
• Inflammation response
  • Contain Damage
  • Localize the response
  • Restore function

How to cells "see" pathogens?

• Receptors recognize shapes or patterns = PAMPs
  • RNA viruses (TLR3, 7, 8)
  • DNA viruses (TLR9)
  • Gram-positive bacteria (TLR1, 2, 6, LTA-TLR2)
  • Gram-negative bacteria (TLR4, Flagellin-TLR5)
  • Fungi (TLR9)
  • Protists (TLR2, 4)

Complement Systems

• Acts in response to stimuli
  • Classical pathway, Lectin pathway, Alternative pathway
• Activation sets off chain reaction, results in destruction or removal of the invader
• Effects of complement activation
  • Opsonization (immune adherence)
  • Enhanced phagocytosis
  • Membrane attack complex (Cytolysis)
  • Attract phagocytes

Next Time

• Adaptive immune system