Chapter 5: Innate Immunity
Anatomical Barriers
● Mechanical barriers
-skin
-mucous
-cillia in lower respiratory tract propels mucus up and out
-flow of urine
,● Chemical barriers
-low pH in stomach
-antimicrobial peptides (defensins, dermicidin, psoraisin)
-Enzymes (lysozyme, amidase)
● Several barriers, both physical and chemical, exist to prevent pathogens from gaining
access to deep tissues
- If those barriers be breached, innate immune system receptors recognize the threat
o Conserved pathogen associated molecular patterns found on microbes
o Or microbe associated molecular patterns
- Aging, dead or damaged self-structures can also be recognized
o Damage-associated molecular patterns
- Pattern recognition receptors recognize these structures and target them for clearance
,Phagocytosis
● Defined as engulfment and internalization of materials such as microbes for their
clearance and destruction.
● Microbes are recognized by receptors on phagocytes
- May recognize PAMPs directly
- May recognize soluble opsonin protein bound to microbes
- Opsonin: a substance (e.g. an antibody or C3b) that promotoes the phagocytosis of
antigens by binding to them.
- Opsonination: deposition of opsonins on an antigen, thereby promoting a stable
adhesive contact with an appropriate phagocytic cell.
● Ingested materials are taken into phagosomes
- phagosomes are fused with lysosomes or granules
● Destruction occurs through enzyme degradation, antimicrobial proteins, and toxic
effects of reactive oxygen species and reactive nitrogen species (ROS and RNS)
, Induced cellular innate responses
● Families of PRRs recognize a wide variety of PAMP ligands
- Toll-Like receptors (TLRs)
- C-type lectin receptors (CLRs)
- RIG-I-Like receptors (RLRs)
- NOD-like receptors (NLRs)
● Signaling pathways are activated, contributing to innate/inflammatory responses
● Toll-like receptors recognize many types of pathogen molecules
- Homologous to fruit fly Toll receptor
- Dimers with extracellular leucine-rich (LRR) domains that bind PAMPs and DAMPs
- Location helps determine what each TLR will bind (expound)