Human Microbiota and Innate Immunity Notes

Human Microbiota and Innate Immunity

• Overview of the Human Microbiome

  • Human body contains approximately ten times more bacterial cells than nucleated human cells.
  • The collection of microbes living on and in the body is known as the microbiota or microbiome.
  • Immune-compromised individuals are vulnerable to opportunistic pathogens.
  • The National Microbiome Initiative was launched in 2016 to enhance understanding of microbiome's impact on health.

• Microbiome Acquisition

  • The microbiome may start developing before birth, possibly acquired from the placenta.
  • Post-birth, newborns encounter diverse microbes from the birth canal and environment, leading to a more diverse microbiome than adults.
  • By age 3, a child’s microbiome resembles that of an adult in diversity.

• The Hygiene Hypothesis

  • Historically, human microbiota thrived in contact with diverse natural environments.
  • Modern indoor lifestyles and extensive use of antibiotics and disinfectants have reduced microbiome diversity.
  • Less diversity is linked to increased inflammatory diseases.

• Resident Microbiota: “Old Friends”

  • These are microbes that usually coexist harmlessly with the host, contributing to immune system development.
  • The immune system learns to identify these microbes as non-threatening, down-regulating immunological responses to them.
  • A failure in this relationship can lead to improper responses to harmful intruders.

• Microbial Associations

  • Divided into Symbiotic (mutualism, commensalism, parasitism) and Nonsymbiotic relationships.
  • Symbiotic relationships may be:
  • Mutualism: both species benefit.
  • Commensalism: one benefits, the other is neither helped nor harmed.
  • Parasitism: one benefits at the expense of the other.
  • Non-symbiotic relationships involve organisms that can live independently and are not dependent on their interactions for survival.

• Innate Immune Response

  • The innate immune system provides immediate defense against infection via physical and chemical barriers, phagocytic cells, and inflammatory responses.
  • Involves the complement system and fever as part of its defense strategy.

• Complement System

  • A series of proteins that enhance (complement) the ability of antibodies to clear pathogens from an organism.
  • Triggered via the classical pathway (antibody-dependent) and alternative pathway (antibody-independent).

• Fever

  • Fever is a natural response to infection, controlled by the hypothalamus.
  • Pyrogens (substances inducing fever) can be exogenous or endogenous, promoting immune response and inhibiting pathogens by reducing iron availability.

• Microbiota's Role in Metabolism and Immunity

  • Microbiota has implications for our metabolism, immune function, and even behavior and cognition.
  • Short-chain fatty acids produced by gut microbiota can influence immune responses.

• Pathogens and Immune Evasion

  • Various mechanisms allow pathogens to evade the immune response, including modifying their antigens or employing strategies to interfere with immune signaling.

• Clinical Implications

  • Understanding the interplay between microbiota and the immune system can lead to improved therapies and preventive measures against infections and inflammatory diseases.