Immunology: Review of The Innate Immune System Flashcards Preview

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Flashcards in Immunology: Review of The Innate Immune System Deck (29)
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1

Why do we need both innate and adaptive immunity to protect us from infection? 

  • 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

What's the difference in specificity betwen innate and adaptive immunity? 

  • 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

What are the components of innate immunity? 

  • Phagocytosis

  • The Inflammatory Response

  • Cytokines, Interferons and Antimicrobial peptides (AMPs)

  • Complement

  • Intrinsic Defences – “the hostile cell”

  • Natural killer (NK) cells

4

What immune system cells carry out phagocytosis? 

  • Dendritic cells  
  • Macrophages 
  • Neutrophils

5

What role do dendritic cells have in innate immunity? 

  • 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

What roles do machrophages have in innate immunity? 

  • 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

What roles do neutrophils have in innate immunity? 

  • 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

What is the inflammatory response? 

  • A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components

9

What things does the inflammatory response cause? 

  • 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

What are cytokines? 

  • 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

What are chemokines? 

  • 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

How do phagocytes know what targets to phagocytose? 

  • 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

What are PAMPs? 

  • 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

What are some examples of PAMPs? 

  • 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

What are pattern recognition receptors (PRRs)? 

  • 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

What are the 3 main functional classes of pattern recognition receptor? 

  • 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

What are some examples of pattern recognition receptors? 

  • Lectin receptors
  • Scavneger receptors 
  • Toll-like receptors 
  • NOD-like receptors 
  • RIG-like receptors (RIG-1 and MDA5) 

18

What was the complement system originally described as? 

  • Originally described as a heat-sensitive component of serum that could augment the ability of antibodies to inactivate antigens 

19

What was the complement system originally thought to lead to? 

  • 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

What do we now know about the complement system? 

  • 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

What do complement proteins act as? 

  • Act as secreted Pattern recognition receptors (PRRs) and can be activated by a range of PAMPs, as well as by “altered self”

22

What are interferons and how do they work? 

  • 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

Describe how the interferon system works? 

  • 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

What are some of the effects of the activation of the various anti-viral response genes in a cell via interferon? 

  • Cell growth arrest 
  • Cell death 
  • mRNA degradation 
  • Translational arrest 

25

What are anti-microbial peptides and how do they work? 

  • 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

Explain the concept of the "hostile cell" 

  • 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

What are natural killer (NK) cells and what is there structure? 

  • 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

How are natural killer cells activated? 

  • 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

Comaprae and contrast the cell types, speed, memory, specificity, receptors and strategy of recognition between innate and adaptive immunity