Immune Recognition I: Innate Receptors Flashcards
what are innate receptors called?
pattern recognition receptors or PRRs
what are the three main categories of receptors of the innate system?
- transmembrane receptors on immune cells
- secreted proteins
- cytoplasmic receptors that are in almost all cells
There are 4 types of receptors in the transmembrane category. Name one.
- Toll-like receptors
- mannose or glucan receptors
- receptors for bacT cell walls
- receptors that bind complement system components
- scavenger receptors that take up macromolecules with a negative surface charge
The secreted proteins category of receptors have two functions…
- bind microbes and tag them for phagocytosis (lectins and complement)
- direct anti-microbial function (defensins)
The cytoplasmic receptor class of receptors includes what?
“nucleotide-binding domain, leucine-rich repeat containing” (NLRs) that bind microbial compounds and stress-associated self molecules and activate response
what is the fxn of the complement system?
recognize and eliminate extracellular microorganisms and promote host inflammatory responses
what is the central biochemical event?
proteolytic cleavage of C3 –> C3a + C3b which then activate two effector response pathways
what does C3a do?
acute inflammatory response:
vasoactive effects, chemo-attractant for phagocytes
what does C3b do?
covalently attaches to microbe
promotes uptake by phagocytes and initiates deposition of pore-forming complex
What are the three pathways that activate complement cascade leading to C3 cleavage?
- alternative pathway
- lectin pathway
- classical pathway
describe the alternative pathway
complement proteases directly activated by factors on surface of microbe resulting in cascade that cleaves C3
describe lectin pathway
plasma protein mannose-binding lectin binds high mannose proteoglycans that initiates the proteolytic cleavage cascade
describe the classical pathway
CRP or certain antibody types bind surface of microbe, a complement component called C1q recruited to surface of microbe.
C1q (stxally similar to MBL leads to C3 cleavage
what are the three effector mechanisms
- anaphylatoxins
- opsonization
- MAC formation
describe anaphylatoxins
low MW fragments from C3, C4, C5 (a versions)
smooth muscle contraction
histamine release from mast cells, enhanced vascular permeability
chemo-attractants for phagocytic cells
describe opsonization
C3b covalently attaches to microbe
microphages and neutrophils recognize C3b and phagocytose
Describe MAC formation
Membrane attack complex
after C3b attaches, cascade continues and 5 different proteins come together to produce a pore-forming unit that lyses bacT
What pathways protect our own cells from complement system?
Factor H and Factor I
cell surface complement-destabilizing proteins
what are factor H and factor I
plasma protein that cleave C3b from cell surface
factor H binds sialic acid so it coats mammalian cells and keeps C3b from binding
what do cell surface complement-destabilizing proteins do?
mammalian cells express cell surface decay-accelerating factor (DAF) and membrane cofactor protein (MCP) that cleave C3b that bind to cell surface
List as many Toll-like Receptor ligands as you can
lipopeptides lipteichoic acid lipopolysaccharide dsRNA (viral) ssRNA (viral) ssRNA (viral) unmethylated CpG-rich DNA GPI flagellin zymosan
Relationship between cell type and type of TLR?
Different cell types have different TLRs
a NK cells will have TLRs for viral recognition, a macrophage will ahve TLR for bacteria
two cellular locations of TLR?
plasma membrane
endosomes
relationship between TLR location and its target?
if its in the endosome, then the target is intracellular (ssRNA, unmethylated DNA, dsRNA)
If it is in the plasma membrane then extracellular (lipopolysaccharide, flagellin, GPI, lipopeptides, lipoteichoic acid, zymosan)
Give an example of TLR co-operation
TLR4 recognizes LPS from G- bacT…
monocytes and macrophages express CD14 that has high affinity for LPS…
CD14 binds LPS, but must come together with TLR4 and MD2 inorder to stimulate intracellular signaling
how does TLR co-operation affect sensitivity?
monocytes and macrophages are highly sensitive to low concentrations of LPS but dendritic cells, mast cells, eosinophils (which do not express CD14) are less sensitive.
How do intracellular signals get transmitted?
adaptor protein acts as bridge to signaling cascades
ultimately, a protein is translocated to nucleus (i.e. NFkB) which is a trx factor that induces inflammation/cytokines/other p
There is an alternative that leads to IRF3 which has different targets than NFkB…innate defense mechanisms…protect against viral infection
