lecture 2 Flashcards
key functions of innate immunity
- prevent, control and eliminate infectious agents
- recognize and eliminate products of damaged/dead host cells -> initiate tissue repair
- stimulate and influence adaptive (special) immune repsonse
components of innate immunity
mechanical barriers chemical barriers physiological factors proteins cells initiates adaptive immune response disruption of innate immunity by microbes :(
mechanical barriers
intact skin
mucosal epithelia & mucus (sneezing, coughing, vomiting, diarrhea)
shedding of infected skins
flushing of bodily fluids (tears, saliva, sweat, pee)
chemical barriers
skin (sebum - sweat)
saliva (lysozyme and antibiotics
mucus (lysozyme and antibiotics)
tears (lysozyme)
DEFENSINS (alpha, beta and gamma - within skin, mucosal epithelial cells, neutrophils and NK cells)
CATHELICIDINS (neutrophils, skin epithelia, GI/respiratory mucosa - will poke hole in pathogen mwhaha)
LACTOFERRIN (bind to iron to create stabber for microbe… decreases RBC production, acute phase protein)
HCl (in stomach)
bile salts and acids
physiological factors
temperature (high fever reduces growth for microbes)
oxygen tension (high O2 makes anaerobic microbes die)
hormonal balance (corticosteroids lead to decreased inflammatory response which could lead to infection)
age (kids and gpas at higher risk to disease bc suboptimal immune systems)
effector proteins
complement mannose binding lectin c reactive protein cytokines (TNF, IL-1, chemokines, IFNalpha, IFNbeta, IFNg, IL12, IL15, IL10, TGFb, IL8) natural antibodies acute phase proteins (lactoferrins)
complement effector protein
kills microbes
opsonization of microbes (through initiating phagocytosis)
activation of leukocytes (WBC)
opsonization
extracellular protein that signals to phagocytizing cell to eat it and KILL, tag cells for phagocytosis
mannose binding lectin
collectin
binds carbohydrates
opsonization of microbes
activation of complement -> lectin pathway
C reactive protein
pentraxin
osponization of microbe
activation of complement
TNF, INL1, chemokines
inflammation
IFNa & b
resistance to viral infection
IFNg
macrophage activation (macrophage cant kill microbe unless activated!)
IL12
NK and Tcells make IFNg (macrophage activation!)
IL15
proliferation of NK cells
IL10, TGFb
control inflammation
IL8
CXCL8 - chemokine
chemoattractant of neutrophils
natural antibodies
made by B cell from fetal liver stem cells (hemopoetic)
acute phase proteins
lactoferrin
inflammation
alarmins
inflammatory molecule as result of damaged cell/tissue
heparan sulfate (repair ECM)
heat shock proteins (repair cytoplasm?)
vasoactive lipids
inflammatory molecule as result of damaged cell/tissue
prostaglandins
leukotrienes
generation of vasoactive lipids from cell membrane
damage to cell/tissue -> phospholipases activated -> cell membrane phospholipids broken -> arachidonic acid -> a. leukotriene -> b. prostaglandin
results in increased vascular permeability and smooth muscle contraction (swelling) or pain and vasodilation
5-lipoxygenase (enzyme for leukotriene)
cycloozygenase (enzyme for prostaglandin)
aspirin inhibits
cyclooxygenase -> so the pain and vasodilation response of prostaglandins is inhibited
steroids inhibit
phospholipase -> so the entire vasoactive lipid pathway is disrupted, no swelling or pain response
LTB4
leukotriene that is involved in chemotaxis for blood leukocytes (neutrophils and eosinophils)
aka triggers cell responders to come kill
LTC, LTD, LTE
leukotriene that increases vascular permeability and smooth muscle contraction aka swelling
neutrophil
effector cell (innate inflammatory response)
early phagocytosis
kills microbes
10^11 produced daily, in instance of infection there are lots of neutrophils produced
macrophage
effector cell - sentinel
secondary phagocytosis to finish the job of neutrophil
kills microbes
secretes cytokines that stimulate inflammation
antigen presenting to T cell!! shows antigen after killing the pathogen which is helpful for future response)
NK cell
lysis of infected cell
activates macrophage through secretion of INFg
sentinel cell
sense tissue damage and recognize microbes
induce inflammation (to localize the infection!)
recruit blood leukocytes via cytokines and chemokines
kill pathogens
dendritic cell
sentinel cell
most important in antigen presenting
<1% of cell type in body
1. capture, process and present antigens to lymphocytes - PROFESSIONALLY - this is how primary immune response initiated
2. provide signals to stimulate T cell proliferation and differentiation
3. secrete cytokines and chemokines (attract leukocytes)
langerhans
interstitial DC
interdigitating DC
circulating DC
mast cell
sentinel cell
secrete: vasoactive amine (histamine & serotonin -> increase vascular permeability & pain) & inflammatory proteins (like cytokines which attract blood leukocytes)
PAMPS
pathogen associated molecular patterns (for recognition done by sentinel cells)
- conserved molecular motifs found ON THE microbes (their signatures) -> stimulate a specific innate immune response once bind to recognition receptor
- detected by pattern recognition receptors (same receptor can bind different microbes
nucleic acids: virus’ and bacteria detecting
proteins: bacteria
cell wall lipids: gram - bacteria
carbohydrates: fungi, bacteria
pattern recognition receptor
can be found in:
soluble (collectins, ficolins, complement, pentraxins)
w/in vesicles (TLR3, 7, 8, 9) - can sense the presence of pathogen from endosome
cytoplasmic (Rig1, NOD like, peptidoglycan receptors, DNA receptors - detect the pathogens PAMPS that hide in cytoplasm)
membrane bound (TLR, lectin, mannose receptor, langerin, dectin, scavenger receptors, integrins - allow cell to recognize an extracellular pathogen)
DAMPS
damage associated molecular patterns produced from stressed of injured host cells
stress induced (heat shock protein)
crystals (monosodium urate)
nuclear proteins (HMGB1 - high mobility group box 1 protein - nuclear proteins that are present around the chromosome)
PAMP-PRR binding
example: LPS (gram - molecular pattern) binds to TLR4 cell membrane protein to signal cytokine release
DAMP disruption activates HMGB1 to trigger endothelium, neutrophil (inflammation -> tissue damage -> shock), macrophages, dendritic cells and epithelium
EqStim
medication that can be used to activate sentinel cell killing mechanisms
prime horses with injection prior to shipping and reduces respiratory infection
same with zelnate
innate vs adaptive
innate: specific for structures shared by groups of related microbes, limited diversity - sticks to germline, no memory, and in not reactive to self
adaptive: specific for antigens of microbes and nonmicrobial antigens, very diverse - receptors are produced by somatic recombination of gene segments, does have memory!, not reactive to self
