Innate Immunity (part 1) Flashcards
in most cases, the initial innate immune response to pathogens is
prevents, controls, or eliminates infection without an engagement of adaptive immunity
if the impact (pathogen load) is signifiant, innate immunity
1.
2.
- keeps the infection in check until more specialized adaptive immune responses are activated
- directs adaptive immunity towards either Ab-mediated or cell-mediated response
innate immunity eliminates host damaged cells and initiates the process of tissue repair that include:
- recognition of host molecules related by stressed, damaged, and/or dead host cells
- phagocytosis and clearance of cell debris
- stimulation and control of tissue remodeling
physical barriers of innate immunity
epithelial layers of skin and mocosal/glandular tissues
chemical barriers of innate immunity
acidic pH of skin (5.5) and anti-microbial proteins and peptides
if intracellular pathogen is present, what innate immune cell takes action
NK cell will kill cell –> releasing pathogens –> that are picked up by phagocytes
activated innate immune cells (e.g. macrophages) produce
- antimicrobial substances (peptides, interferons)
- cytokines and chemokines –> systemic effects (fever); inflammation (recruitment of other cells); and activation of adaptive immune responses
if pathogens overwhelm macrophages, what becomes active
dendritic cells which can then activate adaptive immune responses
opsonization
process by which the pathogen is marked for elimination
neutrophils
polymorphonuclear leukocytes (PMNs)
most abundant of circulating white blood cells
early phagocytosis and killing of microbes
natural killer (NK) cells
lysis of infected cells, activation of macrophages
TNF, IL-1, chemokines
inflammation
IFN-alpha-beta
resistance to viral infection
IFN-gamma
macrophages activation
IL-12
IFN-gamma production by NK cells and T cells
IL-15
proliferation of NK cells
Proliferation of T cells
IL-10, TFT-beta
control on inflammation
innate immunity have the ability to discriminate between _____ and _____
self
nonself
innate immunity discriminate between self and nonself by the mechanism involving _______ and their receptors called ______
pathogen-associated molecular patterns (PAMPs)
Pattern Recognition Receptors (PRRs)
PAMPs (pathogen-associated molecular patterns) have no structural similarity with
self Ags
general properties of PRRs (pattern recognition receptors)
recognize broad classes of pathogens
are encoded in germline (limited diversity)
can discriminate between self and nonself
mannose-tailed glycans are essential surface molecules of
bacteria and viruses
types of PRRs
mannose receptors
N-formyl methionyl receptor
toll-like receptor
general properties of PRRs (pattern recognition receptors)
specificity
receptors
distribution of receptors
discrimination of self and nonself
specificity: for structures shared by classes of microbes (‘molecular patterns’)
receptors: encoded in germline; limited diversity
distribution of receptors: nonclonal; identical receptors on all cells of the same lineage
discrimination of self and nonself: yes; host cells are not recognized or they may express molecules that prevent innate immune rxns
phagocytes use PRRs to help distinguish
self from nonself
PRR-triggered responses of phagocytes:
N-formyl methionyl peptide (fMet) is present in ______ but not in ______
prokaryotes
eukaryotes
polymorphonuclear cells (neutrophils) can bind proteins starting with fMet, and use them to control ______ and initiate ______
motility
phagocytosis
phagocytosis without activation, results in ______ infection
chronic
role of PRRs in phagocytosis
- microbes bind to phagocyte receptors
- phagocyte membrane zips up around microbe
- microbe ingested in phagosome
- fusion of phagosome with lysosome
- killing of microbes by lysosomal enzymes in phagolysosomes and killing by reactive oxidative species and nitric oxide synthase
Pattern Recognition Receptors (PRRs) groups
Toll-Like receptors
intracellular NOD-like receptors
scavenger receptors
lectin family of PRRs
some toll-like receptors (TLRs) are present on the cell surface of innate immune cells where they recognize products of ______ while other TLRs are located in endosomes that recognize which respond only to ______
extracellular microbes
nucleic acids
toll-like receptors that recognize extracellular pathogens
1, 2, 4, 5, 6
toll-like receptors that recognize intracellular pathogens
3, 7, 8, 9
toll-like receptor 2 recognizes
gram-positive bacteria
peptidoglycan
toll-like receptor 4 recognizes
gram-negative bacteria
lipopolysaccaride
toll-like receptors recognize pathogens and actviate
inflammation
each pathogen can be recognized by ______ TLRs
several
TLR1 : TLR2 heterodimer
ligands:
cells carrying receptors:
cellular location of receptor:
ligands: lipopeptides; GPI
cells carrying receptors: monocytes, DC, eosinophils, basophils, mast cells
cellular location of receptor: plasma membrane
TLR2 : TLR6 heterodimer
ligands:
cells carrying receptors:
cellular location of receptor:
ligands: lipoteichoic acid; zymosan
cells carrying receptors: monocytes, DC, eosinophils, basophils, mast cells
cellular location of receptor: plasma membrane
TLR3
ligands:
cells carrying receptors:
cellular location of receptor:
ligands: double-stranded viral DNA
cells carrying receptors: NK cells
cellular location of receptor: endosomes
TLR4 : TLR4 homodimer
ligands:
cells carrying receptors:
cellular location of receptor:
ligands: lipopolysaccharide
cells carrying receptors: macrophages, DC, mast cells, eosinophils
cellular location of receptor: plasma membrane
TLR5
ligands:
cells carrying receptors:
cellular location of receptor:
ligands: flagellin
cells carrying receptors: intestinal epithelium
cellular location of receptor: plasma membrane
TLR7
ligands:
cells carrying receptors:
cellular location of receptor:
ligands: single-stranded viral RNAs
cells carrying receptors: plasmacytoid DC, NK cells, eosinophils, B cells
cellular location of receptor: endosomes
TLR8
ligands:
cells carrying receptors:
cellular location of receptor:
ligands: single-stranded viral RNAs
cells carrying receptors: NK cells
cellular location of receptor: endosomes