Immunology: Review of The Innate Immune System Flashcards
1
Q
Why do we need both innate and adaptive immunity to protect us from infection?
A
- We need innate immuntity as it provides immediate and early protection against pathogens
- We need adaptive immunity as it provides ‘memory’ of an infection which makes it easier to recover next time we’re infected by the same/similar pathogen
- Innate immunity may not be enought to protect us from certain pathogens so adaptive immuntiy also needed
- Adaptive Immunity is too slow to protect us from some new pathogens
2
Q
What’s the difference in specificity betwen innate and adaptive immunity?
A
- Adaptive immunity – Involves very specific recognition of infectious agent (usually sees an antigen on surface of pathogen)
- Innate immunity - Doesn’t involve specific antigen recognition but does involve recognition of broadly conserved features of different classes of pathogens
3
Q
What are the components of innate immunity?
A
- Phagocytosis
- The Inflammatory Response
- Cytokines, Interferons and Antimicrobial peptides (AMPs)
- Complement
- Intrinsic Defences – “the hostile cell”
- Natural killer (NK) cells
4
Q
What immune system cells carry out phagocytosis?
A
- Dendritic cells
- Macrophages
- Neutrophils
5
Q
What role do dendritic cells have in innate immunity?
A
- Detect a pathogen, take it up and then stop any further phagocytosis
- They then move to lymph nodes where they break down the pathogen they’ve taken up
- They then present the pathogens peptides on its surface via MHC class II/I presentation which stimulates adaptive immune response
6
Q
What roles do machrophages have in innate immunity?
A
- Phagocytosis - material is destroyed in lysosomes
-
Captured material can trigger macrophage activation - activated macrophages produce cytokines and chemokines to stimulate both innate and adaptive immune responses
- This triggers the inflammatory response and can promote a local anti-microbial state
- Involved in clearing and repairing damage
- NOTE: Most of them are tissue resident
7
Q
What roles do neutrophils have in innate immunity?
A
- Rarely tissue resident - they’re circulating within bloodstream
- When there’s an infection they get recruited to site of infection/inflammation
- They carry out most of the phagocytosis
8
Q
What is the inflammatory response?
A
- A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components
9
Q
What things does the inflammatory response cause?
A
- Localised infection - stops pathogens frm leaving site of infection
- Removes pathogen via phagocytosis
- Repairs tissue damage from previous infection
- Enhances permeability of endothelium and extravasation
- Neutrophil recruitment
- Enhances cell adhesion - Makes cells sticky which prevents neutrophils from leaving
- Enhances clotting - Creates physical environment which makes it harder for pathogens to spread
10
Q
What are cytokines?
A
- Glycoprotein hormones that affect the immune response
- Act as a very specific signal of a component of the immune response
- Have a very defined narrow role that helps immune system
- Act to modify the behaviour of cells in the immune response
- Most of these are called interleukins (eg. IL-1), some called interferons and TNF
11
Q
What are chemokines?
A
- Glycoprotein hormones that affect the immune response
- Secreted at site of infection like chemokines
- Act as chemotactic factors – they create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection
12
Q
How do phagocytes know what targets to phagocytose?
A
- By detecting phosphatidylserine on exterior membrane surface - Indicates cells undergoing apoptosis as phosphatidylserine located on inside of healthy cell
- By Scavenger receptors -
- By some Toll-Like Receptors (TLRs) - Play very little role in recogniation of material to be phagocytosed
- By passive sampling - At site of infection cells phagocytose things at random (mainly done by neutraphils)
13
Q
What are PAMPs?
A
- PAMPs = Pathogen-associated Molecular Patterns
- Molecules present only on pathogens and not on host cells
- Essential for survival of pathogens
- Invariant structures (can’t be changed) tahte are shared by entire class of pathogens
14
Q
What are some examples of PAMPs?
A
- Gram-negative bacteria - All have lipopolysaccharides (LPSs) found in outer membrane
- Gram-positive bacteria - All have teichoic acid, lipoteichoic acid and peptidoglycan found in outer membrane
- Bacterial flagella
- Abnormal protein glycosylation
- Abnormal nucleic acids - viral nucleic acid slightly different to host cell nucleic acid
15
Q
What are pattern recognition receptors (PRRs)?
A
- Host factors that specifically recognise a particular type of PAMP
- They are germ-line encoded - always express the exact same thing in whatever cell they are expressed in
16
Q
What are the 3 main functional classes of pattern recognition receptor?
A
- Extracellular - They recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen
- Intracellular (cytoplasmic) - They recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen
- Secreted - They act to tag circulating pathogens for elimination
17
Q
What are some examples of pattern recognition receptors?
A
- Lectin receptors
- Scavneger receptors
- Toll-like receptors
- NOD-like receptors
- RIG-like receptors (RIG-1 and MDA5)
18
Q
What was the complement system originally described as?
A
- Originally described as a heat-sensitive component of serum that could augment the ability of antibodies to inactivate antigens
19
Q
What was the complement system originally thought to lead to?
A
- Thought to be a biochemically complex antibody-dependent effector mechanism leading to:
- Opsonisation - Complement gets recruited and forms shell of complement protein around pathogen
- Recruitment of phagocytic cells
- Vasoactive function - Releases peptides which increase permeability of endothelium
- Punching of holes in target membranes - Ocurs via membrane attack system (MAC)
20
Q
What do we now know about the complement system?
A
- Ancient system which predates the development of the adaptive immune response
- Its use as an effector mechanism for the adaptive immune response is an adpation that was grafted onto its original purpose as a vital part of innate immunity
21
Q
What do complement proteins act as?
A
- Act as secreted Pattern recognition receptors (PRRs) and can be activated by a range of PAMPs, as well as by “altered self”
22
Q
What are interferons and how do they work?
A
- Secreted Glycoprotein factors (type I and type III)
- Induced by viral infection - Major part of anti-viral immune response
- Produced during primary infection
- Interferon binds to neighbouring cells that have the receptor for it
- Triggers antiviral state in neighbouring cells
23
Q
Describe how the interferon system works?
A
- Cell infected by a virus
- No immune response against virus in primary infected cell so it’ll apoptose and die
- Primary infected cell also releases lots of new viral particles which attempt to infect neighbouring cells
- However, this doesn’t occur
- This is because interferon produced during primary infection
- It binds to its receptor on neighbouring cells which triggers anti-viral state in those cells
- Does this by promoting Transcriptional activation of >400 antiviral response genes
- This prevents new viral particles from infecting neighbouring cells
24
Q
What are some of the effects of the activation of the various anti-viral response genes in a cell via interferon?
A
- Cell growth arrest
- Cell death
- mRNA degradation
- Translational arrest
25
Q
What are anti-microbial peptides and how do they work?
A
- Anti-microbial peptides (AMPs) are secreted short peptides (18-45 amino acids)
- Usually work by inserting into cell wall and assembling into pores
- This causes disruption of cell wall leading to lysis
- Some are induced by bacterial infection
- Example: Defensins
26
Q
Explain the concept of the “hostile cell”
A
- Cells themselves have biochemical mechanisms that prevent viral replication
- Examples of these biochemical mechanisms include:
- Apoptosis
- Restriction factors/Intrinsic Immunity
- Epigenetic silencing
- RNA silencing
- Autophagy/Xenophagy - removal of unnecessary or disfunctional components/
27
Q
What are natural killer (NK) cells and what is there structure?
A
- Large granular lymphocytes - Lymphocyte-like, but larger with a granular cytoplasm
- Make up 4% of white blood cells
- Kill certain tumour cells and virally-infected cells via cytotoxic molecules called granzymes & perforins
28
Q
How are natural killer cells activated?
A
- NK cells possess the ability to recognise and lyse virally infected cells and certain tumour cells
- Selectivity is conferred by LOSS of “self” MHC molecules on target cell surfaces, and up-regulation of activating ligands
- Uninfected cell
- Normally an uninfected cell would present a peptide to NK cell via MHC class I
- NK Cell recognises peptide presented by MHC Class I
- This acts as inhibitory signal so NK cells won’t kill the uninfected cell
- Infected cell
- Pathogen down-regulates production of MHC Class I resulting in loss of MHC class I on infected cell
- NK cells able to recognise absence of MHC class I (no inhibitory signal)
- This causes NK cell to kill infected cell
29
Q
Comaprae and contrast the cell types, speed, memory, specificity, receptors and strategy of recognition between innate and adaptive immunity
A
