innate immune system Flashcards
specifity of the innate IS
non-speciifc, recognizes DAMP and PAMP so one receptor could bind multiple microbes
receptors of the innate diversity?
non-diverse like the apdaptive
encoded in the germline=limited receptor diversity (100)
distribiution of innate receptors
non-clonal, identical receptors in cells of the same lineage
is the innate non-reative to self?
yes, self cells may display factors to prevent an innate response against them
The two principal types of reaction of the innate immune
system are:
stimulate acute inflamm and innate anti-viral defenses
acute Inflammation.
— which is the accumulation of leukocytes, phagocytic cells, plasma proteins, and fluid derived from the blood at an extravascular tissue site of infection or injury.
Anti-viral defenses mediated by:
- – NK cell-mediated killing of virus-infected cells.
- – Interferon α/β (Type I interferons), which are secreted by virus-infected cells, bind to receptors on surrounding cells, and inducean anti-viral state in those cells.
Prominent cell-associated Pattern Recognition Receptors and
Sensors of Innate Immunity
Toll-Like Receptors (TLRs).
NOD-like Receptors (NLRs).
RIG-like Receptors (RLRs).
where can the innate receptors be located
extracelluar (membrane)
cytosolic
endosome
extracellular innate receptors
lecitin
TLR
cytosolic innate receptors
nod-like receptors
rig-like receptors (scans for viral RNA)
cytosolic dna sensors (should be no DNA here)
endosomal innate receptor
TLR
Toll-Like Receptors (TLRs)
where?
what can they recognize?
located at membrane and endomsome
can recognize bacterial lipoproteins, LPS, peptidoglycan, saccharides and flagellin
can recognize foreign RNA/DNA (ss or ds) within the endosome
Toll-Like Receptors (TLRs) signaling
NOD-like Receptors (NLRs).
NLRs are a family of more than 20 different cytosolic proteins that recognize
PAMPs and DAMPs in the cytoplasm and recruit other proteins to form signaling complexes (such as inflammasomes) that promote inflammation via the production/activation of interleukins
RIG-like Receptors (RLRs).
recognize?
response?
RLRs are cytosolic sensors of viral RNA that respond to viral nucleic acids by inducing production of the antiviral type I interferons.
epithelial barrier of the innate
physical barrier to infection
possess cells that can produce antibiotics to kill microbes
intraepithelial lymphocytes present as well: can kill microbes/infected cells
Phagocytes of the innate
Neutrophils.
…Circulating phagocytic cells; Most abundant leukocytes blood.
…First cell type to respond to most infections.
…Live only a few hours in tissues.
Monocytes/Macrophages.
…Blood monocytes differentiate into tissue macrophages
after entering tissues.
Macrophages:
products/function?
lifespan?
Secrete cytokines that induce inflammation, and ingest and destroy microbes.
Survive for long time periods in tissues
Activation of macrophages
TLR responding to microbe, cytokine receptors and complement receptors can all stimulate the macrophage
TLR activation result at macrohages
cytokine production: stimulate inflamm/ signal to adaptive
phagocyte oxidase activation: kill microbes (via reactive O2 species)
iNOS: kill microbes (via nitric oxide)
Phagocytosis and intracellular killing of microbes within macrophages
microbes binds receptors=endocytosis/ phagosome formed
phagosome fuses with lysosome
microbe killed with ROS, nitric oxide, and lysosomal enzymes
Dendritic cells (sentinel cells) functions
…Secrete cytokines.
…Present antigenic peptides to T cells.
Mast cells granules? where found? contain? cause?
…Abundant cytoplasmic granules.
…Present in skin and mucosal epithelium.
…contain vasoactive amines (e.g. histamine).
…cause vasodilation and capillary permeability
Innate lymphoid cells function
…lymphocyte-like cells.
…produce cytokines but lack T cells antigen receptors (TCRs).
- Complement functions
…Induce inflammation, opsonize microbes enhancing their phagocytosis, cause osmotic lysis of microbes.
complement paths/ activation mech
alternative: microbe binds the receptor
classical: ab binds microbe
lecithin: mannose bonds lecitihin
early complement steps/ function
all paths converege to cleave c3 to a and b fragments
a: inflammation
b: opsinitzation/ phago
late complement steps/ fucntion
c5 cleaved to a and b
a: inflammation and recruitment of c6-9 to form the MAC for osmotic lysis of microbe
what is inflammation/ how does it occur
Delivery of neutrophils, macrophages, T lymphocytes, complement proteins, antibodies, and acute-phase reactants to the site of inflammation is due to reversible changes in blood vessels in the infected or damaged tissue:
- increased blood flow into tissue due to arteriolar dilation
- increased adhesiveness of circulating leukocytes to the endothelial lining of venules
- increased permeability of capillaries and venules to plasma proteins and fluid
changes associated with inflammation due to?
All these changes are induced by cytokines and small molecule mediator initially derived from sentinel cells (resident phagocytic cells) in the tissue, as well as endothelial cells, in response to stimulation of PAMPs or DAMPs
Sequence of events in migration of blood leukocytes to sites of infection
The sequence of selectin-mediated rolling, chemokine-dependent integrin-mediated firm adhesion, and chemokine-mediated motility leads to the migration of blood leukocytes to the extravascular site of infection.
Rolling> binds selectin> integrin activation via chemokines> stable adhesion> migration thru endothelium
Natural Killer (NK) cells function/secretion?
..Kill virus-infected cells presenting nonself peptides at MHC or no MHC
…Secrete interferon γwhich activates macrophages to kill phagocytosed microbe
Activating and inhibitory receptors of natural killer (NK) cells
prevent destruction: activating receptor of NK binds activating ligand but the inactivation receptor binds MHC I with self peptide present
cell destruction: only activating receptor binds ligand, no MHC present
- IFN α/β (Type I Interferons)
…Secreted by virus infected cells, induce anti-viral state in surrounding cells.
Antiviral actions of type I interferons
Cytokines of innate immunity
many different proteins: TNF, IL, INF, etc.
made by many different cells
multiple effects possible from these
Role of Innate Immunity in Stimulating Adaptive Immune Response.
innate occur first and can produce molecules to simulate the adaptive response
two signal requirement for lymphocyte activation: microbial Ag must bind Ag receptor and molecule induced form innat response will bond a receptor as well, both these lead to lymphocyte prolif and dif
how Extracellular bacteria and fungi are combated by the innate
mainly by an acute inflammatory response, in which neutrophils and monocytes are recruited to the site of infection, and by the complement system.
how Intracellular bacteria is combated by the innate
Intracellular bacteria, which can survive inside phagocytes, are eliminated when the microbial killing functions of phagocytes are activated by Toll-like receptors and other sensors, as well as by cytokines.
innate viral defense
Defense against viruses is provided by type I interferons (interferons α and β) and by natural killer (NK) cells.
