Review of Innate Immunity Flashcards
What does adaptive immunity involve?
β very specific recognition of an infectious agent (usually a protein)
What does innate immunity involve?
β no specific antigen recognition
β recognition of broadly conserved features of different classes of pathogens
What are the 6 components of innate immunity?
β Phagocytosis β The inflammatory response β cytokines, interferons and antimicrobial peptides (AMPs) β complement β intrinsic defences 'the hostile cell' β NK cells
What immune feature do all multicellular organisms have in common?
β means to recognise and phagocytose debris and infected cells
What cells is phagocytosis carried out by in vertebrates?
β dendritic cells
β macrophages
β neutrophils
What cells do most of the phagocytosis at the site of infection?
β neutrophils
What do neutrophils do in chronic inflammation?
β they do a lot of tissue damage during chronic inflammation
What two things does phagocytosis do?
β clears pathogens
β presents peptides on MHC
What does phagocytosis promote?
β development or reactivation of the adaptive immune response
How is material destroyed in phagocytosis?
β in lysosomes
Where are macrophages found?
β in tissues
What can trigger macrophage activation?
β captured material
What do activated macrophages produce?
βcytokines and chemokines to stimulate both innate and adaptive immune responses
What do the products of activated macrophages trigger and what does this promote?
β the inflammatory response and can promote a local antimicrobial state
What is the main purpose of macrophages?
β clear and recruit other cells to the site of infection
What is the purpose of the inflammatory reponse?
β localise and eliminate injurious agents and to remove damaged tissue components
What are the 4 things that occur during the inflammatory response?
β Enhanced permeability of endothelial cells and extravasation
β neutrophil recruitment into the cell
β enhanced cell adhesion
β enhance clotting
What are cytokines and chemokines?
β Glycoprotein hormones that affect the immune response
What do cytokines do?
β act to modify the behavior of cells in the immune response
What are most cytokines called?
β Interleukins
What do chemokines do?
β act as chemotactic factors
β they create concentration gradients which attract or occasionally repel specific cell types to a site of production/infection
What does a macrophage secrete when it is infected?
β IL-8
What does TNF alpha do?
β opens the endothelium and triggers an anti-viral response
What 2 cells types is IL-1 produced by?
βmacrophages and keratinocytes
What is the effect of IL-1 and IL-6?
β induces acute-phase protein secretion
What 2 cell types produce IL-6, IL-8, and IL-12?
β macrophages and dendritic cells
What is the effect of IL-8?
β chemoattractant for neutrophils
What is the effect of IL-12?
β Diverts the immune response to type 1
β proinflammatory cytokine secretion
What are the 4 ways in which phagocytes know what to phagocytose?
β detecting phosphatidylserine
β scavenger receptors
β toll-like receptors
β passive sampling
What cells do passive sampling?
β neutrophils
When is phosphatidylserine expressed in cells?
β when they are undergoing apoptosis
What are PAMPs?
β molecules present only on pathogens and no host cells
β invariant structures share by entire class of pathogens
β pathogen-associated-molecular-patterns
What is a gram negative PAMP?
β lipopolysaccharide found in the outer membrane
What are 3 gram positive PAMPs?
β teichoic aicd
β lipoteichoic acid
β peptidoglycan found in the outer membrane
What are 3 other PAMPs?
β bacterial flagellin
β abnormal protein glycosylation
β abnormal nucleic acids - viruses
What are PRRs?
β pattern recognition receptors
β receptors for PAMPs
What are PRRs encoded by?
β germline
What are the three classes of PRR?
β extracellular
β intracellular
β secreted
What do extracellular PRRs recognise and do ?
β recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen
What do intracellular PRRs recognise and do?
β PAMPs inside a cell and act to co-ordinate a response to the pathogen
What do secreted PRRs do?
β tag circulating pathogens for elimination
What is the PAMP ligand for lectin receptors and what is the outcome when it is recognised?
β terminal mannose and fucose
β phagocytosis
What is the PAMP ligand for scavenger receptors and what is the outcome when it is recognised?
β Bacterial cell walls and modified low-density lipoproteins
β phagocytosis
What are the 6 PAMP ligands for toll like receptors?
β LPS with CD14 β lipoproteins β unmethylated CpG βflagellin β dsRNA β ssRNA
What is the outcome when toll like receptors recognise PAMPs?
β Inflammation and cytokine release :TNF, IL-1, IL-12
β enhanced killing : reactive oxygen species, NO
β Phagocytosis
What are the two PAMP ligands for NOD like receptors?
β peptidoglycan from gram + and gram -
What is the outcome when NOD like receptors recognise PAMPs?
β inflammation and cytokine release : IL-1, IL-8
What are the 2 PAMP ligands for RIG like receptors?
β DsRNA and 5β triphospho-RNA
What is the outcome when RIG like receptors recognise a PAMP?
β Type 1 interferon production
β apoptosis
What is the definition of the complement?
β heat-sensitive component of serum that can augment the ability of antibodies to inactivate antigens
What three things does complement activation lead to?
β Opsonisation
β recruitment of phagocytic cells, vasoactive function
β punches holes in target membranes
What do complement proteins act like?
β act as secreted pattern recognition receptors (PRRs)
In what two ways can complement proteins be activated?
β a range of PAMPs
β βaltered selfβ
What are the three classical pathways of complement?
β Classical pathway
β Lectin pathway
β Lack of host control pathway
How does the classical complement pathway work?
β through antigen-antibody complexes
β the triggering protein is C1q
β C1q recognises lipopolysaccharides
What does the lectin pathway recognise?
β Recognises abnormal glycosylation
What does the lack of host control pathway recognise?
β anything that is not of host origin
What are interferons induced by and what do they offer?
β induced by viral infection
β cross-protection
Describe how interferon stops viral proteins being made?
β a cell is infected by a virus
β the virus replicates
β the cells apoptose and die and release a lot of virus which attempts to invade the neighbouring cells
β during the primary infection interferon is produced and secreted
β it binds to the cells that have a receptor for it
β it triggers an antiviral state in those cells
βit turns on antiviral response genes which are not normally expressed
β protein kinase R is usually inactive
β if a virus gets in and replicated it produces a lot of double stranded RNA which activated protein kinase R
β this switches off the ribosomes
β the virus cannot produce more proteins
How do antimicrobial peptides work?
β disrupting the cell wall leading to lysis
How are antimicrobial peptides induced?
β bacterial infection
What are antimicrobial peptides?
β secreted short peptides (18-45 amino acids)
What are 5 features of the intrinsic defences of the cells?
β Apoptosis β restriction factors/intrinsic immunity β epigenetic silencing β RNA silencing β autophagy/xenophagy
What % of white blood cells are natural killer cells?
β 4%
What is the function of natural killer cells and how do they do this?
β they kill tumour cells and virally infected cells
β caused by cytotoxic molecules called granzymes and perforins
What are the 3 cell types in the innate immune system?
β macrophages
β neutrophils
β dendritic cells
What are the cell types in the adaptive immune system?
β lymphocytes
Which one of innate and adaptive retains memory?
β adaptive
Which one has higher specificity : innate or adaptive?
β Adaptive
What receptors does the innate immune system use?
β pattern recognition
What receptors does the adaptive immune system use?
β Ig and TCR
What is the recognition strategy of the innate immune system?
β Small number of microbial ligand that are highly conserved between pathogens
β germ line encoded receptors that have evolved by natural selection
What is the recognition strategy of the adaptive immune system?
β Billions of possible antigens
β receptors are generated randomly within an individual and they cannot be inherited
Which is the faster out of innate and adaptive?
β innate
