Review of innate system Flashcards
Why is the adaptive immune system not apt for new pathogens?
→too slow
Compare innate and adaptive immune system
→Adaptive immunity – involves very specific recognition of infectious agent
→Innate immunity – no specific antigen recognition
→Innate immunity involves recognition of broadly conserved features of different classes of pathogens
How is pattern recognition done in innate response?
→PAMPs
What are PAMPs?
→Molecules present only on pathogens and not on host cells
→Essential for survival of pathogens
→Invariant structures shared by entire class of pathogens
What type of bacteria have PAMPs?
→gram negative or positive
Example of PAMPs in gram negative bacteria
→lipopolysaccharides (LPSs) outer membrane
Examples of gram positive bacteria cell wall components
→teichoic acid
→lipoteichoic acid
→peptidoglycan found in outer membrane
What are other PAMPs?
→Bacterial flagellin
→Abnormal protein glycosylation
→Abnormal nucleic acids - viruses
What are PRRs?
→Host factors that specifically recognise a particular type of PAMP
How are PRRs encoded?
→germ line encoded
→no rearrangement unlike antibodies
What are the 3 types of PRRs?
→Extracellular
→intracellular
→secreted
What are secreted PRRs?
→they act to tag circulating pathogens for elimination
→eg complements
What are the components of innate immunity?
→The inflammatory response →Phagocytes Monocytes/granulocytes/neutrophils →Complement →Cytokines, chemokines and anti-microbial peptides (AMPs) →Natural Killer cells
What is an inflammatory response?
→localize and eliminate injurious agents and to remove damaged tissue components
What are the features of inflammatory response?
→Enhanced permeability and extravasation
→Neutrophil recruitment
→Enhanced cell adhesion
→Enhance clotting
What is the inflammatory response trigger?
→the release of pro-inflammatory cytokines and chemokines
What is the difference between cytokines and chemokines?
→cytokines enhance inflammatory
→chemokines act to create chemical concentration gradient for neutrophils to migrate to
What are TLRs not involved in?
→phagocytosis
What is a distinct feature of phagocytic recognition?
→they use different pattern recognition receptors
What are neutrophils involved in?
→Neutrophils involved in tissue damage not involved in priming adaptive response
What are the three distinct roles of macrophages and dendritic cells?
→Phagocytosis; material is destroyed in lysosomes
→activated macrophages produce cytokines and chemokines
→Peptides from broken down pathogens can be presented through MHC and promote the development or recall of an adaptive T cell response
How do Phagocytes know what to eat?
→By detecting phosphatidylserine on exterior membrane surface (cells undergoing apoptosis)
→By detecting “atypical sugars” (e.g. mannose, fucose, b-glucan) on cell surfaces
→By Scavenger receptors
→By “passive sampling”
→By detecting complement
proteins bound to the
pathogen surface
What are examples of atypical sugars?
→mannose,
→fucose,
→b-glucan
Which virus doesn’t present phosphatidylserine?
→Ebola
What is the complement system?
→Complement proteins act as secreted Pattern recognition receptors (PRRs)
→can be activated by a range of PAMPs, and can also be activated by “altered self”
Which organ makes the complement system?
→liver
What are the PAMP targets of the complement system?
→antigens →LPS →abnormal phospholipids →atypical glycosylation →lack of host control factors
What are the three pathways of complement system?
→The Classical Pathway
→The Mannose-Binding Lectin Pathway
→The Alternative Pathway
What is the classical pathway of complements?
→activated when a complement protein called C1q binds either directly to a pathogen, or onto an antigen-antibody complex
What do all the pathways have in common?
→produce C3 convertase
What is the MBL/ficolins pathway?
→detect carbohydrates containing mannose on the surface of pathogens,
→activating a protease called MASP
→MASP is responsible for cleaving complement components
→activates cascade
What is the alternative pathway of the complement system?
→activated by bacterial endotoxin
→lipopolysaccharide present on the outer membrane of gram negative bacteria
How do Phagocytes know when they are infected and when to produce cytokines and chemokines?
→PAMPs are recognised by a distinct group of Pattern Recognition Receptors
What are the PRRs on phagocytes?
→TLRS
→NOD-like
→RIG like
What is the TLR ligands?
→LPS
→Unmethylated CpG- viral infection
→flagelin
→dsRNA or ssRNA
What is the outcome of TLR activation?
→inflammation: cytokine release (TNF, IL-1, IL-12)
→enhanced killing: reactive oxygen species, NO)
What are the ligands for NOD-like receptors?
→Peptidoglycan from Gram positive and negative bacteria
→Some viral DNA and RNA (indirect?)
What is the outcome of NOD-like receptors?
→inflammation: cytokine release (IL-1, IL-8)
What is the outcome of RIG-like receptors?
→type I interferon production
What is the ligand for RIG-like receptors?
→Viral dsRNA and 5’-triphospho RNA(inproperly capped)
What are cytokines?
→Act to modify the behaviour of cells in the immune response
→Most of these are called interleukins (eg. IL-1)
What do type 3 interferons protect?
→epithelial surfaces
What are interferons induced by?
→viral infection
How are interferons released?
→Secreted hormone factors (type I and type III)
What are anti-microbial peptides?
→Secreted short peptides (18-45 amino acids)
→Offer broad protection
→Some are induced by bacterial infection
How do anti-microbial peptides work?
→by disrupting cell wall leading to lysis
What are NK cells?
→Lymphocyte-like but larger with granular cytoplasm
What pathogens do NK cells kill?
→certain tumour
→virally infected cells
How do NK cells cause destruction?
→cytotoxic molecules called granzymes & perforins
How are NK cells activated?
→loss of self MHC molecules on target cell surfaces
→upregulation of ligands
What are the two types of complement core defects?
→core defects (e.g. C3) linked to development of autoimmune diseases such as lupus
→non-core defects linked to suseptibility to specific types of pathogens such as Neisseria
What are two macrophage deficiencies?
→Chronic granulomatous disease (CGD); No oxidative burst for bacterial killing
→IRF8 mutations linked to susceptibility to TB
What is Aicardi-Goutieres syndrome?
→associated with constitutive production of inflammatory cytokines
What are the receptors used in innate and adaptive immunity?
→innate= pattern recognition →adaptive= Igs and TCR
