Innate Immunity 1 Flashcards
what is innate immunity?
non-specific, no lasting memory, first line of defence against the oral microbiota
what are the stages of innate immunity immediately after infection?
recognition by performed, non-specific and broadly specific effectors - removal of infectious agent
what are the stages of early induced innate response after infection?
recruitment of effector cells - recognition of PAMPs, activation of effector cells and inflammation - removal of infectious agent
what are the 5 groups of disease causing agents?
bacteria, viruses, fungi, protozoa, helminths
what do disease symptoms depend on?
where the pathogen replicates and the damage it causes
when is the innate immune response effective?
with regular contact with potential pathogens which are destroyed within minutes or hours, only rarely causing disease
what cells contribute to innate immune response?
epithelial/endothelial cells + fibroblasts
how does epithelium contribute to innate immunity?
it is a physical barrier and produces antimicrobial peptides, cytokines and chemokines
what are the innate cell subsets and complement?
phagocytic cells (macrophages and neutrophils) and antigen-presenting cells (dendritic cells)
what is the function of chemokines?
cell recruitment
what is the function of cytokines?
cell activation/proliferation
what are the different main components of innate immunity?
epithelium, innate cell subsets and complement, chemokines/cytokines
what is produced by the epithelium in the oral cavity?
antimicrobial peptides, immunoglobulins (secretory IgA), lactoferrin, lysozyme and cystatins
what do antimicrobial peptides do?
attach and disrupt membranes
when are antimicrobial peptides effective?
in low concentrations
what are the major families of the antimicrobial peptides?
beta-defensins, human neutrophil peptides, cathelicidins, psoriasin proteins
what are the two different functions of antimicrobial peptides?
directly kill microbes and modulate host immunity
how do antimicrobial peptides directly kill microbes?
there is an electrostatic interaction between the two cells, the AMP ruptures the membrane OR inhibits intracellular function both causing bacterial lysis
what are the different ways in which AMPs modulate host immunity?
recruit or activate immunocytes, neutralise bacterial products to suppress inflammation, enhance nucleic acid recognition to promote auto-inflammation
where is secretory IgA produced?
at mucosal surfaces
what does secretory IgA do when binded to a flagella?
prevents motility
what does secretory IgA do when it is binded to a bacterial toxin?
it neutralises it
how does secretory IgA prevent effects of microbes on mucosa?
it cross links target macromolecules and bacteria and prevents attachment of bacteria to mucosal surfaces
what is lactoferrin and what does it do?
glycoprotein that transports iron ions but has antimicrobial activity
where is lactoferrin present and what is it produced by?
present in saliva and produced by neutrophils
where are lysozymes present and what are they produced by?
present in saliva and produced by macrophages/neutrophils
what do lysozymes target?
cell walls of bacteria
what is the function of cystatins?
they have anti-protease activity and support re-mineralisation of the teeth
what are the salivary components that have antimicrobial activity?
AMPs, secretory IgA, lactoferrin and antimicrobial activity
what do cell surface TLRs recognise?
different compounds of bacterial or fungal cell wall/membrane
what do intracellular TLRs recognise?
internalised viruses
what are the two main TLRs to remember?
TLR2 and TLR4
what are the main type of microbial receptors?
toll-like receptors
what is the function of toll-like receptors?
primarily for bacterial and viral recognition
apart from TLRs what other receptors are there?
dectin and glucan receptors, NOD-like receptors, protease-activated receptors
what do dectin and glucan receptors recognise?
fungus
what do NOD-like receptors recognise?
bacteria
what do protease-activated receptors recognise?
microbial and allergen recognition
what are the main roles for receptors?
promote phagocytosis of microbes and activation of immune cells
overall what are microbial receptors?
pattern recognition receptors (PRRs) that recognise pathogen associated molecular patterns (PAMPs)
what do cellular mechanisms include?
both the epithelium as well as the innate immune cells that patrol the epithelium
what can cytokines do?
instruct all immune cells what to do
what are cytokines?
small proteins which are signalling molecules which co-ordinate immune responses
what are the different cytokine families?
interleukins, TNFs, interferons and unassigned
what are interleukins?
a class of cytokines
how are interleukins divided up into group?
it depends on the functions of each family member as some are pro-inflammatory and some anti-inflammatory
what are the 3 main functions of cytokines?
autocrine, paracrine and endocrine
what is the autocrine function of cytokines?
alter behaviour of cell from which they were secreted from
what is the paracrine function of cytokines?
alter behaviour of neighbouring cells
what is the endocrine function of cytokines?
enter circulation and alter behaviour of distant cells
where are the cytokine receptors?
on the target cells
what does cytokine binding induce?
a conformational change in a majority of receptors intracellularly
what does signal transduction lead to?
the activation of transcription factors that leads to control of gene regulation
overall what do cytokines and chemokines do?
shapes type of immune response
overall what do antimicrobials do
protection against invading organisms
overall what do growth factors do?
tissue remodelling and repair
overall what are receptors responsible for?
differentiation and proliferation
what are chemokines?
small signalling proteins
what is chemotaxis?
the movement of a cell in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance
what are chemokines involved in?
recruitment (directing)
what is the difference between chemokines and cytokines?
chemokines tell cells where to go and cytokines tell cells what to do
what are the 4 classes of chemokines?
C (2 members), CC (31 members), CXC (18 members) , CX3C (1 member)
what are the 4 classes of chemokines dependent on?
their first 2 cysteine residues
where are chemokine receptors?
on a range of innate and adaptive immune cells
what is the main chemokine to play a role at the oral mucosa?
CXCL8
what are pathological features of a certain disease dependent on?
over or under reaction of the immune system
what compounds does the oral mucosa produce to prevent infection?
AMPs, Secretory IgA, lactoferrin, lysozyme and cystatins
overall what are Pattern Recognition Receptors?
a variety of receptors that recognise unique features of microbes
