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1

INNATE IMMUNITY OVERVIEW

i) when is it present and how is it encoded? what does this mean?

ii) how long does it take for it to respond upon pathogen recognition?

iii) what happens if you are lacking innate immunity?

iv) if a pathogen is not elimited by preformed soluble/effector molecules - what is activated? what timeframe does this have effect in

v) if that pathogen is still not cleared - what is activated?

i) present at birth and germline encoded - means it doesnt change much over life

ii) minutes

iii) lacking innate - dont block any micro-organism growth

iv) activate induced innate response - 4 hours to 4 days

v) pathogen still not cleared > activate adaptive 

2

CHARACTERISTICS OF INNATE IMMUNITY 

i) does it trigger an immediate response?

ii) what does it recognise? what does it interact with?

iii) does it require gene rearrangement? does it have clonal distribution? is it encoded in multiple gene segments?

iv) can it discriminate between closely related molecular structures 

i) yes

ii) recognises broad class of pathogens and interacts with molecular structures

iii) no gene rearrange/clonal expan/multiple gene seg encoding 

iv) yes 

3

INNATE IMMUNE MEMORY 

i) what are the only organisms to have adaptive immune memory?

ii) name three organisms that have innate immune memory

iii) name three components of an innate response when an organism gets infected with a pathogen? what do all these responses lead to? 

iv) what happens if an organism if re challenged with the same pathogen 

i) only vertebrates have adaptive

ii) plants, inverts, verts

iii) epigenetic changes eg modification of histones, production of micro RNA and long non coding RNAs
- these all affect gene expression 

iv) re challenged - the organism can have a boosted response which is antigen independent 

 

4

INNATE BARRIERS TO INFECTION 

i) what is the first barrier? name three components

ii) name three components of the soluble barrier 

iii) if the soluble barrier can eliminate the pathogen, what is activated? name three components of this 

i) physical - skin, GI tract, respiratory tract

ii) soluble - complement, defensins, collectins

iii) soluble then induced innate response
- innate immune cells, PRRs and inferon 

5

ANATOMICAL BARRIERS

i) which chemical barrier is found throughout the whole body?

ii) which mechanical barrier is found throughout the whole body?

iii) what does pulmonary surfactant in the lungs contain that acts as a barrier?

iv) which microbiological barrier is found throughout the body?

i) antimicrobial peptides

ii) epithelial cells joined by tight junctions

iii) surfactant contains collectins 

iv) normal microbiota 

6

TISSUE DAMAGE 

i) what does tissue damage cause the release of? (2) what does this trigger (2)

ii) what happens to capillaries? 

iii) what is the name of the process where phagocytes migrate to site of inflammation?

iv) what is the name of the process by which cells move out of the capillaries and into the tissues?

i) damage causes release of vasoactive and chemotactic factors which trigger increased blood flow and increased cap permeability 

ii) capillaries become more permeable 

iii) phagocytes migrate > inflamm = chemotaxis

iv) cells move out of the tissues = extravasation 

7

SOLUBLE INNATE IMMUNE MOLECULES 

i) what do lysozymes do? which two fluids are they found in (2)

ii) where are antimicrobial peptides found? what do they do?

iii) what do collectins, ficolins and pentraxins do? (2)

iv) name three roles of complement components 

i) lysozyme > disrupts bacterial cell walls
- found in blood and tears 

ii) antimicrob peptides found all over the body
- disrupt microbial membranes

iii) bind to pathogens and target them for phago
- activate complement 

iv) lyse bacteria, opsonise bacteria and induce inflammation 

8

LYSOZYME

i) name two cells its secreted from

ii) what does it disrupt? what type of bacteria does this happen in?

iii) how does it cause the disruption? 

iv) once the lipid bilayer is exposed - what can disrupt the phospholipids?

v) which type of bacteria is it less effective against? why?

i) phagocytes and paneth cells in the SI

ii) disrupts peptidoglycan in bacterial cell wall
- most effective in gram positive bacteria

iii) cleaves the bond between alternating sugars that make up the PG

iv) phopholipase A2 can disrupt the phospholipids 

v) less effective against gram negative bacteria as its covered in LPS which masks the PG therefore lysozyme cant get to it

9

ANTIMICROBIAL PEPTIDES

i) what surfaces do they cover? name a fluid they are found in

ii) name three cell types that secrete them? what is the pattern of secretion?

iii) how quickly do they kill bacteria? how do they do this? (2) 

iv) name two other micro-organisms they may attack

 

 

 

i) cover epithelial surfaces and found in saliva

ii) secreted from neutrophils, epithelial cells and paneth cells 
- constituitively secreted 

iii) kill bacteria in minutes (avg 90 mins)
- do this by disrupting the membrane and inhibiting DNA/RNA synthesis 

iv) can also attack fungi and viruses 

10

FAMILIES OF ANTIMICROBIAL PEPTIDES 

i) where are histatins produced? which type of MO are they active against?

ii) what cathelicidin is found in humans? what is it active against?

iii) what are the two classes of defensins? what situation are these important in?

i) histatins are produced in the oral cavity 
- active against pathogenic fungi eg candida

ii) cathelicidin = LL-37
- broad spectrum activity against both gram pos and neg bacteria

iii) defensins = alpha and beta
- important in newborn to defend against first encounter of microbes eg from the vagina during birth 

11

DEFENSINS

i) are small or big? are they hydrophobic or hydrophilic?

ii) which bonds stabilise the structure? how do they do this?

iii) what do defensins do to the microbe? what does this lead to?

iv) do they act on our cells?

i) small peptide 
- amphipathic (both hydrophil and hydrophob) 

ii) disulphide bonds stabilise the structure as to seperate the positive charged and the hydrophobic region of the defensin

iii) defenins disrupt microbial cell membranes by inserting themselves into the membrane and forming a pore
- pore causes sugar/ions to move out and water to move in causing cell lysis

iv) no 

12

COLLECTINS/FICOLINS/PENTRAXINS

i) how do all three of these induce the innate immune response?

ii) what is the structure of the head/tail of collectins? what do the heads bind on the bacteria? why dont collectins bind host cells?

iii) which is the ficolin head made of? what do they recognise? give an example of what they recognise and where it is found 

iv) what type of proteins are pentraxins and where are they found? give a clinically relevant example - what does this bind to on bacteria?

i) activate complement 

ii) collectins have globular lectin like head an collagen tail
- heads bind bacterial cell surface sugars 
- sialic acid hides mannose antigens on host cells

iii) ficolin head is made of fibrinogen 
- recognise acylated compounds such as n-acetylglucosamine which is found in bacterial cell walls 

iv) pentraxins are cyclic multimeric proteins found in plasma
- CRP > binds phosphocholine on bacterial surfaces 

13

ACTION OF COLLECTINS, FICOLINS AND PENTRAXINS 

i) what type of receptors do they have?

ii) what can they act as that allow cells to be targeted for phagocytosis?

iii) which two pathways do they activate complement through?

iv) which class of molecule is mannose binding lectin?

i) pattern recognition receptors

ii) act as opsonins that bind pathogens/infected cells 

iii) activate complement through classical or lectin pway

iv) MBL is a collectin 

14

COMPLEMENT PATHWAY AND C3

i) which molecule to all three pathways converge on?

ii) name three downstream events after this?

iii) name a molecule that activates the classical pathway

iv) name two molecules that activate the lectin pathway 

v) what activates the alternative pathway?

i) C3 convertase

ii) phagocytosis, inflammatory events, lysis of infected cell

iii) CRP 

iv) collectins and ficolins

v) pathogen surfaces 

15

THE COMPLEMENT SYSTEM 

i) what is it?

ii) what happens when complement proteins detect foreign material?

iii) once activated, what do proteins aim to do?

iv) where are most proteins made? give three other cells they are produced by

i) series of 30+ proteins that constantly circulate in blood and fluids that bathe body tissues

ii) detect foreign mat > initiate cascade of reactions that amplify the signal 

iii) activated > generate inflammation and rapidly remove the pathogen 

iv) most proteins are made by the liver
- also produced by monocytes, macrophages, epithelial cells in intestine and urinary tract 

16

COMPLEMENT COMPONENTS 

i) how do they circulate in the blood? why is this?

ii) what type of activity do some have? 

iii) what happens when they are activated? what does this trigger?

i) circulate in the pro-form (inactive) as they are a powerful inducer of inflammation 

ii) some have proteolytic enzymatic activity (are serine proteases)

iii) on activation they split into small and large fragments which triggers an amplification cascade 

17

COMPLEMENT CASCADE

i) what do all three pathways converge on? what then happens?

ii) which protein does C5 convertase come together with to make C5? 

iii) what is the terminal stage of the complement cascade? 

iv) name a molecule that induces each of the three pathways 

 

i) all converse on C3 convertase 
- this causes C3 > C3a and C3b

ii) C5 convertase comes together with C3b to make C5

iii) terminal stage = membrane attack complex

iv) CRP (pentraxin) or antigen antibod complexes > classical
- collectins and ficolins > lectin pathway
- microbial surfaces > alternative pathway 

18

EFFECTORS MEDIATED BY COMPLEMENT COMPONENTS

i) what can complement componets directly cause to a cell?

ii) name three things that complement proteins can mediate in relation to phagocytes

iii) what does the membrane attack complex do? 

iv) where are immune complexes transported to once bound to complement components? what happens here?

i) can cause cell lysis 

ii) complement proteins can opsonise, activate inflam response (extravasation and degran of mast cells) and clear immune complexes

iii) MAC forms pores in the memrbane of pathogens and causes lysis

iv) once immune complexes are bound to complement proteins they are transported to the liver where phagocytes remove and break them down 

19

CLASSICAL PATHWAY 

i) what role does C1 play?

ii) which three proteins is C1 made up of? which one makes up the stalk and most of the molecule? 

iii) how many polypeptides is the stalk? what do these form?

iv) what region of the antibody antigen complex does C1 bind?

i) initiates the classical pathway when activated 

ii) C1 = C1q, C1s and C1r
- C1q makes up most of the molecule and forms the stalk

iii) 18 polypeptide stalk that forms six collagen like triple helix structures 

iv) C1 binds the fc region of antibody/antigen complex 

20

CLASSICAL PATHWAY ACTIVATION 

i) what does C1 bind to trigger it?

ii) how many of these must C1 bind for activation?

iii) what is the most efficient immunoglobulin at activating this pathway? why?

iv) which three other immunoglobulins can also activate complement? what is needed for these to activate it? why?

v) in what conformation can IgM not bind C1? what is needed for it to bind?

i) C1 binds the fc domain of antigen/antibody complexes

ii) at least 2 fc domains must bind

iii) IgM is most efficient at activating pathway as it has 5 fc domains on one molecule

iv) IgG1, IgG3 and IgG2 can also activate complement
- need lots of IgG molecules on pathogen for activation to make sure there are two that are close enough together to bind C1 at the same time 

v) IgM cant bind C1 in its planar conformation
- needs to change conform > crab like structure to reveal binding site for C1q

21

AMPLIFICATION OF THE CLASSICAL PATHWAY 

i) what does the binding of C1q and Fc domain cause?

ii) cleavage of C1 can activate which two complement components? how are these activated?

iii) which fragments of these come together to make C3 convertase?

iv) what does C3 convertase then activate? how does it do this? what does this result in?

v) what three fragments form C5 convertase? what does c5 convertase do? what does this ultimately result in?

i) binding of C1q and Fc domain causes a conformational change in C1r

ii) cleavage of C1 activates C2 and C4
- activated by splitting into large and small frags 

iii) C2a and C4b come together to make C3 convertase

iv) C3 convertase then activates over 200 C3 molecules to produce a massive signal amplification 

v) C3 convertase (C2aC4b) and C3b fragments form C5 convertase > membrane attack complex 

22

LECTIN PATHWAY 

i) is this pathway antibody dependent or independent? give two things its activated by 

ii) what does mannose binding lectin bind on carbohydrates? what does it bind on bacteria/some viruses? what does this activate

iii) which two serine proteases does MBL form a complex with when it binds? what two proteins does this leave to the cleavage of?

i) antibody independent 
- activated by mannose binding lectin and ficolins 

ii) MBL binds mannose on carbohydrates
- binds glycoproteins in bacteria/some viruses
- this activates similar ds mechs to classical pathway

iii) MBL forms a complex with MASP-1 and MASP2 serine proteases > cleavage of C2 and C4 (to C3 convertase etc) 

23

ALTERNATIVE PATHWAY 

i) what complement protein does it start with? what happens to it?

ii) which fragment binds the pathogen cell membrane? what factor can it come across to make it susceptible to cleavage by factor D? 

iii) what is the cleavage product? what is the half life of this

iv) which serum protein can extend the half life by 30 mins? how does it do this?

v) what effect can the cleavage product have on C3? what does this allow? 

vi) which molecule an alternative form of C3 convertase in this pathway?

i) starts with C3 > hydrolyses to C3a and C3b when it comes into contact with a microbial cell surface 

ii) C3b binds pathogen cell membrane and if it comes across factor B = susceptible to cleavage by factor D

iii) cleavage product is C3bBb (C3b + factor B) 
- half life of 5 mins

iv) serum protein properdin can extend the half life to 30 mins by protecting it from serum proteases 

v) C3bBb can hydrolyse more C3 and therefore amplify the signal 

vi) C3bBb is an alternative form of C3 convertase here 

24

TERMINAL COMPLEX COMPONENTS

i) which molecule is the start of the common terminal pathway?

ii) what fragment of C5 joins with C6,7,8,9? what does this form?

iii) how does MAC kill a cell? (3)

iv) why don't MACs target human cells?

i) C5 convertase 

ii) C5b joins C6,7,8,9 to form the membrane attack complex 

iii) MAC forms a pore that inserts into the cell membrane
- allows diffusion of ions and small molecules out
- water moves into the cell > kills it

iv) MACs dont target human cells as they have soluble and cell surface proteins that prevent MAC formation 

25

COMPLEMENT INHIBITORS

i) what type of proteins may these be? (2) 

ii) what are the three types?

iii) what do MAC inhibitors do? 

iv) what condition is caused by C1 inhibitory deficiency? what happens? how can it be treated?

i) can be soluble or membrane bound

ii) C1 inhibitor, C3 inhibitors, MAC inhibitors 

iii) MAC inhibitors prevent insertion of MAC into the membrane

iv) C1 inhibitory deficiency > Hereditary angioedema 
- classical complement cascade is easily activated and leads to lots of oedema in face and lips 
- treat with an injection of C1 inhibitor 

 

26

COMPLEMENT DEFICIENCY 

i) what do patients deficient in components of complement pathway experience?

ii) what can MBL deficiency cause in neonates and children?

iii) which deficiency is the most severe? what does it lead to?

iv) which infection are patients deficient in C8 prone to?

i) deficiency in any part > recurrent infections 

ii) MBL defic can cause serious pyogenic infections (pus forming) in neonates and children 

iii) C3 deficiency is most severe > successive severe infecs

iv) C8 deficiency are prone to neisseria meningitis 

27

COMPLEMENT DEFICIENCY IN SLE 

i) which complement protein are 90% of SLE patients deficient in?

ii) why does this deficiency lead to lower C3b levels?

iii) what receptor does C3b normally bind on erythrocytes? what happens to the RBCs once this has bound?

iv) in SLE what triggers heightened innate immune response and production of pro inflam cytokines?

i) C4 deficiency 

ii) C4 deficiency leads to lower levels of C3b as C4b is a part of C3 convertase (less C4 = less C3 > C3b)

iii) C3b normally binds CR1 on erythrocytes which transports them to phagocytes in liver and spleen > phagocytes recog immune complexes via FC receptors and engulf them

iv) in SLE - patients have lots of autoantibodies that bind to own DNA/RNA which triggers immune response