BIOL 435 Ch. 4 Part One (Innate Immunity) Flashcards
defenses against infection
- Chemical barriers
- Anatomical barriers
- Cellular responses
* fast or immediate induction
chemical barriers
- antimicrobial substances
- acid pH
anatomical barriers
-epithelilum
>skin
>mucosa
>glandular tissue
cellular responses
- 2 line of innate defense
- leukocytes for phagocytosis
- release of proteins
- NK cells
if barriers are breached
-innate immune system receptors recognize the threat
>conserved pathogen-associated molecular patterns (PAMPs) found on microbes
DAMPs
- damage-associated molecular patterns
- aging, dead, or damaged self structures can also be recognized
PRRs
- pattern recognition receptors
- recognized PAMPs and DAMPs
3 steps of protection
- Physical and chemical barriers to infection
- Cellular responses to infection
- Activation of adaptive immune responses
epithelial layers
-produce protective substances >acidic pH >enzymes and binding proteins >antimicrobial peptides *prevent pathogen entry into the body's interior >skin >mucosal membranes
sebum
- wax product produced in pores on skin
- keeps skin moisturized
eg. acne
antimicrobial proteins
-lysozyme
-lactoferrin
-S100 proteins
>psoriasin
>calprotectin
lysozyme
- mucosal/grandula secretions
- cleaves glycosidic bonds of peptidoglycan in cell walls of bacteria, leading to lysis
lactoferrin
- mucosal/grandular secretions
- binds and sequestors iron
- limit growth of bacteria and fungi
- disrupts microbial membranes
- limits infectivity of some viruses
S100 proteins
- skin
- mucosal/grandular secretions
- disrupts membranes, killing cells
- binds and sequesters divalent cations
- limiting growth of bacteria and fungi
antimicrobial peptides
- <100AA long
- evolutionarily ancient
- cysteine-rich, cationic, amphipathic
- disrupt membranes of pathogens
- enter cells and inhibit synthesis of DNA, RNA and proteins
ex. defensins, dermcidin
defensins (alpha and beta)
- skin
- mucosal epithelia
- disrupt membranes
- additional toxic effects intracellularly
- kills cell and disable viruses
dermcidin
- skin (from sweat glands)
- antibacterial and anti fungal
- produces channels in membranes that disrupt ion gradients
2nd line of innate defense
-families of PRRs recognize a wide variety of PAMP ligands
-PRRs can be intracellular or on cell membrane
*binding of PRR to PAMP results in signalling pathways becoming activated
>contributes to innate/inflammatory responses
PRR locations
- myeloid leukocytes
- lymphocytes
- epithelial cells of skin, mucosa and glandular tissues
- vascular endothelial cells
- stromal cells
Toll-like receptors (TLRs)
- recognize many types of pathogen molecules
- homologous to fruit fly Toll receptor
- dimers with extracellular leucine-rich domains that bind PAMPs and DAMPs
- location helps determine what each TLR will bind
LRR
- leucine rich repeats
- in TLRs
plasma membrane TLRs
- TLR 4/4
- TLR 2/1
- TLR 2/6
- TLR 5/5
- TLR 11/11
- TLR 12/12
- face outwards
endomsomes/lysosomes TLRs
- TLR 4/4
- TLR 3/3
- TLR 7/7
- TLR 8/8
- TLR9/9
- face inwards
mice only TLRs
- TLR 11/11
- TLR 12/12
- TLR 13/13
human only TLR
-TLR 10/10
TLR 4/4
- PM: gram negative bacteria
- endosomes: viral proteins
TLR 2/1
- only form of TLR 1
- bacteria
- parasites
TLR 2/6
- only form of TLR 6
- gram positive bacteria
- fungi
TLR 5/5
-bacterial flagellin
TLR 11/11
-uropathogenic bacteria
TLR 12/12
-toxoplasma profilin
TLR 3/3
-viral dsRNA
TLR 7/7
-viral ssRNA
TLR 8/8
-viral ssRNA
TLR 9/9
- bacterial/viral DNA
- plasmodium
gram negative bacteria
- display lipopolysaccharides (LPS) on cell surface
- peptidoglycan is ‘hidden’
ex. E.coli
gram positive bacteria
- have a thick layer of peptidoglycan at cell surface
ex. S. aureus
TLRs recruit different adapter proteins
-to the Toll/IL-IR (TIR) domain
-leads to different events
>ex. transcriptional factors
-result is altered gene expression (upregulation of appropriate effectors)
