1. Basics: Innate Immunity Flashcards
what is innate immunity
the primary response to pathogen invasion, components include both anatomical barriers as well as cellular responses
describe the specificity of the innate immune system
rather than recognise a specific pathogen - the innate immune system recognises classes of organisms
how are innate immune receptors encoded, what does this mean?
germline ended - means they are highly conserved and do not undergo random recombination unlike adaptive immunity receptors
list 5 cells involved in innate immunity
neutrophil
macrophage
dendritic cell
eosinophil
natural killer cell
when does the innate immune reaction begin
hours following invasion
describe the anatomical barrier
the epithelial layer that lines skin, mucosal and glandular tissue
name 2 mucosal tissues
respiratory and gastrointestinal tract
name 2 glandular tissues
salivary and mammary glands
what is the purpose of tight junctions
prevent pathogens penetrating the barrier between cells
what are mucins
a glycoprotein that prevents pathogen adherence to epithelial cells
name 2 purposes of mucus
chemical barrier containing natural antimicrobials
offers false binding sites for bacteria and viruses
describe the composition of vaginal secretions
acidic pH mucus that provides protection against fungal and bacterial infections
what maintains the acidic pH of the vagina
lactic acid released from commensal lactobacteria
which layer of the skin forms the physical barrier
keratinocytes at the top layer
describe an example of evolutionary resistance to epithelial barriers that has emerged in some pathogens
influenza A firmly attaches its surface glycoprotein (haemagglutinin A) to sialic acid expressed on the epithelial surface sialic acid receptor. This prevents it being swept out the respiratory tract by ciliated epithelial cells.
name 2 antimicrobial proteins
lysozyme
lactoferrin
where is lysozyme and lactoferrin found
in mucosal and glandular secretions
how does lysozyme act
cleaves glycosidic bonds of peptidoglycan in cell walls of bacteria = lysis
how does lactoferrin act
binds and sequesters iron = this limits the growth of bacteria and fungi
name 2 antimicrobial peptides
defensins
dermicidin
where are defensins found
skin, mucosal epithelia
how do defensins work
use electrostatic attraction to insert itself into the lipid bilayer where is can disrupt the membrane and act intraceullarly to kill cells and disable viruses
where is dermicidin found
skin (from sweat glands)
how does dermicidin work
produces channels in membranes that disrupt iron gradients = antibacterial & antifungal
how does the microbiome layer protect the host from pathogens
competition for space - commensal microbiota colonise a niche thus preventing pathogenic bacteria from gaining a foothold and producing toxins
define phagocytosis
the uptake of particulate materials (e.g. pathogens, dead cells) by a cell
name 3 types of phagocytes
neutrophils
macrophages
dendritic cells
how are neutrophils different from macrophages
after phagocytosing neutrophils undergo cell death
macrophages and dendritic cells act as APCs after engulfing
name 3 roles of phagocytes
kill pathogens and take up cell debris
detect PAMPs and secrete cytokines
act as APCs to activate B and T cells
where are PRRs found
on the surface, in the cytosol and on the endosome
PRRs activate signalling cascades, this leads to the production of what (3 things)
interferons
cytokines
chemokines
what are interferons used in
viral infection
what is the role of chemokines
recruit cells to the site of infection
list 3 DAMPs
heat shock proteins
DNA
beta amyloid
what does DAMPs stand for
damage-associated molecular patterns
name the 2 membrane associated PRRs
toll-like receptors
c type lectin receptors
name 2 cytosolic receptors
nucleotide-binding doman and leucine-rich repeat receptor (NOD-like receptor)
RIG-I like recetors
what is the ligand of TLR4
lipopolysaccharide (Gram -ve bacteria)
which TLR detects gram +ve bacteria
TLR2 detects peptidoglycan in Gram +ve membranes
which TLR detects ss viral RNA
TLR7
what is the outcome of TLR signalling
NF-kB activation
what is NF-kB
a transcription factor that drives production of cytokines
in response to viral protein TLR4 is activated, what does this in turn result in the production of
phosphorylation of IRF-3 or IRF-7 = result in the transcription of type 1 interferons
what type of ligands to CLRs recognise
carbohydrate ligands
once a CLR is activated, what kinase do they signal through? and what is the result?
kinase SYK and CARD9
= result in the production of pro-inflammatory cytokines and ROS
where are CLRs typically expressed
on macrophages or DCs
what are NLRs most highly expressed by
macrophages
what do NLRs require
inflammasome activity
name 4 proinflammatory cytokines
IL-1 beta
TNF- alpha
IL-6
CXCL8
how does TNF-alpha act
induces blood vessels to become more permeable - allowing effector cells to enter infected tissue
what is the role of IL-6
induces fat and muscle cells to metabolise = creates heat and raises the temp of the infected tissue
what is the role of CXCl8
recruits neutrophils from the blood guiding them to the site of infection
how does IL-12 act
recruits and activates NK cells
- these cells further produce cytokines to enhance the macrophages response to infection
what does RLR signalling lead to
type 1 interferon production
what does the cGAS-STING pathway sense
cytosolic DNA
what are the two types of interferon signalling
autocrine (acting on the same cell)
paracrine (neighbouring cell)
name 3 actions induced by IFNs
increase MHC class 1 expression and APC in all cells
activate dendritic cells and macrophages
activate NK cells to kill-virus infected cells
what 2 types of gremline encoded receptors does NK cells possess
inhibitory receptors
activating receptors
what molecules do inhibitory receptors detect
self molecules, e.g. MHC 1
- When MHC I is down-regulated by viruses, this is detected as “missing self”.
what molecules do activating receptors detect
detect MIC-A and MIC-B expressed on epithelial cells that have detected a virus , “altered self”
once activated what do NK cells release
granules containing performs and granzymes which kill the target cell
what is the role of langerhans cells
resident phagocytes in the skin
what causes autoinflammation
over-production of pro-inflammatory cytokines
what causes interferonopathies
over-production of type 1 interferons by the innate immune system
