Review of the Innate System Flashcards
Why do we need the inante immunity?
Adaptive immune response is too slow to protect us from some new pathogens
How long do antibodies and cytotoxic T cells take to begin to be seen in a new infection?
- Antibodies start around 5 days but take longer to accumulate
- Cytotoxic T cells start to rise on day 3/4 and peak soon
- So a fast replicating organism could form huge numbers in the first few days if it weren’t for innate immunity
What is the major class of antiviral cytokines?
Interferon
What does the innate immunity recognise?
PAMPs
Innate immunity can not recognise specific antigens such as proteins, so it instead recognises broadly conserved pathogenic features such as structural features of a cell wall
What is a PAMP?
Pathogen Associateed Molecular Pattern
is NOT a specific antigen like what the adaptive immune response identifies, it is broad pathogenic features
Name some features of PAMPs
- Molecules present only on pathogens and not on host cells
- Essential for survival of pathogens
- Invariant structures shared by entire class of pathogens
Name some PAMPs for gram positive bacteria
- Teichoic acid
- Lipoteichoic acids
- peptidoglycan found in outer membrane
Name a PAMP for gram negative bacteria
Lipopolysaccharides (LPSs) found in outer membrane
What PAMPs can we recognise for viruses as they do not have a cell wall?
They do not have a cell wall but we can recognise abnormal nucleic acids (or abnormal protein glycosylation also?)
What is meant by how PRRs are germ-line encoded?
They do not change unlike in T cells or B cells that rearrange their T or B cell receptors
What do PRRs recognise?
PAMPs
Name the 3 functional classes of PRRs
- Extracellular - recognise PAMPs outside cells
- Intracellular/cytoplasmic - recognise PAMPs inside a cell
- Secreted - tag circulating pathogens (like complement)
What is complement?
- A type of PRR that is secreted
- The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism.
Broadly describe the purpose and effects of the inflammatory response
- A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components
- Enhanced permeability and extravasation
- Neutrophil recruitment
- Enhanced cell adhesion
- Enhance clotting
- Triggered by the release of pro-inflammatory cytokines and chemokines at the site of infection
Which WBCs are mostly recruited in inflammation?
Neutrophils
What are some requirements of phagocytes?
- need to be able to recognise what to eat
- need to know when they are infected
They do this by 2 SEPERATE mechanisms (they use different PRRs)
Name 3 professional phagocytes
Dendritic cells, macrophages and neutrophils
What are the 3 distinct roles of macrophages and dendritic cells in immunity?
- phagocytosis
- macrophages produce cytokines and chemokines to + innate and adaptive response and local inflammation
- MHC antigeen presentation (promote or recall of an adaptive T cell response)
What marker do phagocytes detect on an apoptotic cell?
Phosphatidylserine on the exterior membrane
This is a way of detecting virus-infected cells as an infected cell will usually apoptose
Macrophages detect atypical sugars such as {{?}} on cell surfaces
mannose, fucose and beta glucan
What are scavenger receptors?
Detect non-self markers, detect various PAMPs and DAMPs
What are scavenger receptors?
Detect non-self markers, detect various PAMPs and DAMPs
What is macrophage passive sampling?
Taking in small globules of ECF and sampling it for pathogens
{{?}} receptors are found on phagocytes to aid in the take up of complement-coated pathogens
Complement receptors are found on phagocytes to aid in the take up of complement-coated pathogens
Why is it called complement?
Bc it complements antibodies to inactivate antigen
Name 3 functions of complement
- Opsonisation
- Recruitment of phagocytic cells, vasoactive function
- Punches holes in target membranes
What are the different pathways?
- Classical
- Lectin
- Alternative
TLRs (toll like receptors) are expressed on {?} of phagocytes and {?}
TLRs (toll like receptors) are expressed on the surface of phagocytes and facing inwards on endosomes
Do TLRs or NLRs detect viruses?
TLRs as they are on the endosomes so a virus after being engulfed is detected that way
Name some targets (ligands) of TLRs
- LPS
- Lipoproteins
- Flagellin
- dsRNA, ssRNA (in endosomes) for viruses
Where are NLRs found in the phagocyte?
NLRs are in the cytoplasm (not endosomes)
Name some targets (ligands) of NLRs
- Peptidoglycan from Gram positive and negative bacteria
- Some viral DNA and RNA
- Cytoplasmic PRRs
What is the name of the receptor type of phagocytes that is predominantly for recognition of viral infection
- RIG-like
- cytoplaplasmic
Name some targets of RIG-like receptors
Viral dsRNA (we never produce dsRNA) - inproperly capped RNA
Once there is binding of TLRs, NLRs or RIG-like receptors, what happens?
Release of specifc chemokines or cytokines from the phagocyte
What are most cytokines (but not all) called?
Interleukin (then a number)
What is the name of the main anti viral cytokine type?
Interferons
What does type 3 secreted interferon do?
Protective of epithelial surfaces like lungs
What does type 1 secreted interferon do?
Protects other surfaces like the blood and tissues
Explain how the interferon system works
Infected cells with a virus release interferon which causes other cells to adopt an anti-viral state (upregulates antiviral genes)
What pathway does IFN alpha/beta use to upregulate antiviral genes?
JAK/STAT
What is the effect of interferon on protein kinase R?
Upregulates it
How is protein kinase R activated?
viral dsRNA is a cofactor for protein kinase R so activates it
What is the effect of protein kinase R?
Full translational arrest of the cell and also the viral components in the cell
What are defensins?
These are short antimicrobial peptides that are secreted to kill bacteria
How do defensins usually work?
Disrupting cell wall leading to lysis of bacteria
- some are induced by bacterial infection
- offer broad protection
Do interferons and defensins offer specific or broad protection?
Broad - they are part of the innate IS
- do not bind to any sort of specific antigens, but have a general antiviral/antibacterial response
Describe the properties of natural killer cells (what are they)
- 4% white blood cells
- Lymphocyte-like but larger with granular cytoplasm
Describe the properties of natural killer cells (what are they)
Certain tumour cells and virally infected cells
What do natural killer cells kill?
Certain tumour cells and virally infected cells
How do natural killer cells kill their targets?
By cytotoxic molecules called granzymes and perforins - inject them in. Also by Fas
Explain how natural killer cells know which cells to kill
By identifying a cell as having a ‘loss of self’
- done in multiple ways
Fully explain the mechanism of how NK cells detect loss of self cells that they will kill
NK cells will recognise MHC class 1 (which is on basically all cells) which will present random antigens
- if it detects MHC1 and an antigen then it does nothing
- many pathogens (particularly viruses) downregulate MHC1 as it is used for antigen presentation
- if NK cell does not bind to MHC1 then it kills the cell
Diseases associated with inherited defects in innate immunity
Describe the difference between innate and adaptive immunity in terms of cell types, speed, memory, specificity, receptors and strategy of recognition
