Lecture 10 Innate Immunity Flashcards
immunity present before any exposure from pathogen
effective from time of birth
immunity
first line of defense is composed of
innate immunity
skin
mucosal membranes and their secretion
normal flora
second line of defense
innate immunity
phagocytosis (NK cells) (neutrophils, eosinophils, DCs, macrophages)
inflammation
fever
antimicrobial substances
what is the third line of defense?
Adaptive immunity
specialized t cells and b cells
Abs
chemical barriers of innate immunity
defenses
lysozyme
complement
active in opsonization
qualities of skin that make it a strong microbial barrier
it is a tough physical barrier (hard to get in)
dry, salty environment, acidic (hard to survive)
Lysozyme
works by cleaving Nag/Nam (bond connecting sugars) in peptidoglycan
effective against gram + cells
ciliary escalator
mucous secretions trap microbes and pushes them away from lungs
either towards throat (for digestive system) or into mouth to be coughed out
goal is to keep them out of respiratory system
where is lysozyme found?
tears
secretions
mucous
what keeps the lower respiratory system sterile
ciliary escalator
alveolar macrophages – phagocytes of lungs
prevent microbes from growing here
what parts of the body are sterile
lungs
bladder (kidney to bladder)
what can be found in the stomach that prevent infection
gastric acid
what can be found in the intestines that prevent infection
pancreatic enzymes bile intestinal enzymes GALT peristalsis \shedding of epithelium secretory IgA normal microbiota paneth cells
Paneth cells produce
produce lysozyme
produce cryptins
what do they eyes have to prevent infection
mucus secreting membrane
Tears: lysozyme, lactoferrin, secretory IgA
lacrimal apparatus that flushes microbes
sebum
forms protective acidic film over skin surface to inhibit microbes
first line of defense
saliva
lysosome, urea, uric acid to inhibit microbes
IgA to prevent microbe attachment to membranes
slightly acidic to discourage microbial growth
first line of defense
gastric juices
destroys bacteria and toxins in stomach
first line of defense
vaginal secretions
slightly acidic to discourage bacterial and fungal growth
first line of defense
inflammation
confines and destroys microbes
imitates tissue repairs
second line of defense
NK cells
kill infected target cells by releasing granules of perforin and granzymes
they then kill infected microbes
antimicrobial substances of second line of defense
complement
interferons
iron binding proteins
effects of complement activation
opsonization (phagocytosis)
membrane attack complex (cytolysis)
attract phagocytes
How do NK cells know which molecules to target?
Fc receptors– bind to Fc cells on Ags
where do all three complement pathways converge?
C3 Convertase
C3a, C5a result
mediate inflammation (stimulate histamine release)
phagocyte recruitment
C3b result
opsonization of pathogens (enhances phagocytosis)
removal of immune complexes
C5b, C6, C7, C8, C9
form MAC
leakage of cytosol –> lysis
what is released by complement that stimulates inflammation
histamine
how do bacteria evade complement
capsules (prevent C activation so no complement)
inhibition of MAC formation
enzymes that target C5a (no inflammation so no phagocytosis)
complement protein deficiency would be worse for which protein?
C3
all complement would activity cease
IFN- a and IFN -B
geared for viruses
cause cells to produce antiviral proteins that inhibit viral REPLICATION
don’t neutralize virus itself
IFN-Y
geared for bacteria
causes neutrophils and macrophages to phagocytize bacteria
how do IFN- a and IFN -B work?
they don’t alter the virus itself, instead they inhibit viral replication of neighboring cells so virus can’t spread
where do TLRs bind?`
PAMPs
what do IFN- a and IFN -B secrete to prevent attack on neighboring cells?
antiviral proteins (AVPs)
these cells prevent attack viral transcription in neighboring cells
what are structures unique to microbes that we use to group them?
PAMPS
example of PAMPS
peptidoglycan
LPS
flagellin
what recognize PAMPs on phagocytic cells?
PRRs
esp. TLRs
what type of PRRs function exclusively as signaling receptor?
TLRs
what is the ultimate outcome of PAMP-TLR activation
signals inflammation
mechanism of intracellular digestion
- phagocytic cells take up bacteria
- delivers it to lysosome = fusion
- formation of phagolysosome
- breakdown and release of reactive oxygen species
- microbes are killed
mechanisms of microbial evasion
inhibition of adherence (M protein, capsules)
kill phagocytes (leukocidins)
lyse phagocytes (MAC)
escape phagosomes
prevent phagosome and lysosome fusion
grow in phagolysosome
inflammation
innate – nonspecific response to tissue injury
caused by pathogen or trauma
release of mediators to control
cardinal signs of inflammation
redness warmth pain swelling altered function
pyrogenic response
Fever
caused by endotoxin release and phagocytotic induction of IL-1
IL-1 stimulates hypothalamus to release prostaglandins and raise temperature
IL-1 is removed and body temps decline
advantages of fever
t cell production (due to IL-1)
increase transferrins
speed up repair process
disadvantages of fever
acidosis (via increased metabolic rate)
dehydration
tachycardia
death
chemicals released by damaged cells
histamine
kinins
leukotreinces
prostaglandins
histamine
vasodilation
increases permeability of blood vessels
this is why we take anti histamines
prostaglandins
intensity of histamine and kinin effect
vasodilation and increased BV permeability
