Innate immunity Flashcards
Does innate immunity require prior exposure to Ag?
Nope
What are 4 types of innate immunity?
Physiological barriers
-> Temperature, low pH
Physical barriers
-> Skin, mucous membrane
Cellular factors
-> Macrophages, neutrophils
Humoral factors
-> Complements, acute phase proteins
What are the 2 factors released when there is tissue damage?
Vasoactive factor
Chemotactic factors
What does vasoactive factor do?
Increase capillaries membrane permeability
Increase blood flow to affected area
What does chemotactic factor do?
Attracts cells ( e.g. neutrophils & monocytes ) to area where it is released ( e.g. Area of tissue damage )
What are 4 types of intracellular killing?
Phagocytosis
Receptor mediated endocytosis
Pinocytosis
Autophagy
What is NETs / NETosis? (Neutrophil extracellular traps)
Neutrophil throws its own DNA out
-> Lysosome attached to DNA neutralizes target pathogen
- -> Might affect nearby friendly cells
Does dog / cat has a lot of kupffer cell / lung macrophage?
Dog
-> Kupffer cell ( Liver )
Cat
-> Lung macrophage
What are 3 types of oxygen independent killing?
Lytic enzymes
Antimicrobial peptides
-> Defensins
TNF
What are 2 types of oxygen dependent killing
ROS
-> O2-
RNS
-> NO
Which of the following is essential for producing ROS for antimicrobial usage?
ATP
NADH
NADPH
GTP
NADPH
Where can NADPH be found for aiding in the production of ROS?
Membrane
Which of the following are essential for RNS production?
NOS2
iNOS
iPhone
NOSE
NOS2
iNOS
Where is iNOS found?
cytosol
Which of the following a.a. is essential for RNS production?
Alanine
Arginine
Lysine
Tyrosine
Arginine
What is the difference between M1 and M2 macrophage?
M1
-> early inflammatory
-> produces RNS
-> MHC - 2 expression
M2
-> late inflammatory
-> tissue repair
-> increased MHC - 2 expression
Which lymphocyte peforms innate defensive mechanism?
NK cell
Which are the 2 signature cell that does intracellular killing / extracellular killing?
Intracellular killing
-> Macrophage
-> Neutrophil
Extracellular killing
-> NK cell
-> Eosinophil
What are the 3 humoral factors?
Complement
Acute phase protein
Interferon
What are the 3 functions of complements?
Cell lysis
Opsonization
Chemotaxis
-> Neutrophil
-> Eosinophil
What is the definition of acute phase protein?
Protein synthesized in liver
-> response to inflammatory
What are 2 acute phase protein that can activate complements?
CRP
-> C - reactive protein
MBL
-> Mannose - binding lectin
What are 3 types of interferon ( IFN )?
IFN - alpha
IFN - beta
IFN - gamma
What cells releases IFN - gamma?
NK cell
Th1
Tc
What are 4 categories of molecules that connects innate and adaptive immunity?
PRRs
-> Pattern recognition receptors
PAMPS
-> Pathogen - associated molecular patterns
DAMPS
-> Damage - associated molecular patterns
Inflammation
What are 2 sub categories in PRR?
Soluble proteins
Membrane proteins
What are the 4 soluble proteins in PRR?
Complements
Humoral factors
-> CRP
-> MBL
-> LBP
- -> LPS - binding protein
Who are the 3 inflammatory brothers?
TNF - alpha
IL - 1 beta
IL - 6
What is the definition of PAMPs?
molecules produced by microbial invaders
What is the definition of DAMPs?
molecules
-> released from damaged , dead or dying cells & tissue
-> produced by sentinel cells
- -> macrophages, dendritic cells, mast cells
What does DAMPs do?
Recruit & activates cells of innate immune system
Promote adaptive immune responses
What determines if neutrophil survives?
Expression of CD31 by neutrophil
What happens if neutrophil doesn’t express CD31?
Phagocytosis of neutrophil
-> By macrophage
Which organ synthesizes complements & acute phase protein?
Liver
What are the name of the 3 pathways that activates complements?
Classical
Lectin
Alternative
What is the 2 main components in classical pathway?
( complement activation )
Ag - Ab
C1
Which 2 antibodies can activate complements?
Which one is better at activating complements?
IgM > IgG
What is the main component in lectin pathway?
MBL
What is the main component in alternative pathway?
C3, Factor B & Factor D
Which complement is part of the membrane - attack complex?
C5b
C6
C7
C8
C9 ( A LOT )
What is the first complement involved in classical pathway?
C1
-> C1qr2s2
Classical
What activates C1 (C1qr2s2) in classical pathway?
Immune complex
-> Ag - Ab
Classical
What does activated C1 do?
Cleave C4 => C4a + C4b
-> C4a
- -> small
- -> floats in circulation
-> C4b
- -> big
- -> stays on pathogen’s membrane
Classical
What does activated C1 after C4b is detected?
Cleave C2 => C2a + C2b
Classical
What does C4b & C2b form?
C4b2b
-> C3 convertase
Classical
What does C4b2b ( C3 convertase ) do?
Cleave C3 => C3a + C3b
Classical
What does C4b2b & C3b form?
C4b2b3b
-> C5 convertase
Classical
What does C4b2b3b ( C5 convertase ) do?
Cleave C5 => C5a + C5b
Lectin
What activates MBL?
MBL ( mannose - binding lectin )
-> contact w/ surface mannose of pathogen
Lectin
What does MBL bind to when activated?
MASP ( MBL - associated seine protease )
-> similar function to activated C1
Lectin
What does MASP do after binding to MBL?
Cleave C4 => C4a + C4b
Lectin
What does MASP do after detecting presence of C4b?
Cleave 2C
-> The rest is the same as classical pathway
Alternate
What is the first molecule activated in alternate pathway?
C3
Alternate
How is 3C activated?
Attachment to pathogen?
Alternate
What happens when C3 attaches to pathogen wall and get activated?
Hydrolyses itself
-> cleave C3 => C3a + C3b
Alternate
What happens after C3b is present?
Cleave Factor B => Ba + Bb
-> Factor D helps cutcut
Alternate
What does C3b + Bb form?
C3bBb
-> C3 convertase
Alternate
What does C3bBb ( C3 convertase ) do?
Cleave C3 => C3a + C3b
Alternate
What does C3bBb + C3b form?
C3bBb3b ( C5 convertase )
Alternate
What does C3bBb3b ( C5 convertase ) do?
Cleave C5 => C5a + C5b
What happens after C5b is produce by the 3 pathways?
C5b binds C6
-> C5b6 binds C7
- -> C5b67 binds C8
- - -> C5b678
What happens after C5b678 is formed?
C9 polymerization
-> Poly C9 surrounds C5b678
- -> Complete membrane attack complex is formed
What are the 3 timing for regulating the complement system?
Before assembly of C3 convertase
After assembly of C3 convertase
Assembly of membrane - attack complex (MAC)
What are the 6 regulatory factors before assembly of convertase activity?
C1 inhibitor
C4bBP ( C4b - binding protein )
Factor I
CR1 ( Complement receptor 1 )
MCP ( Membrane cofactor protein )
Factor H
What is the function of C1 inhibitor in classical pathway?
C1 inhibitor binds to C1r2s2
-> causes dissociation from C1q
What is the function of C4bBP in classical pathway?
Blocks the binding of C4b + C2b => C4b2b
Which 2 regulatory factors other than C4bBP that can block binding of C4b & C2b in classical pathway?
CR1
MCP
What is the function of Factor I in classical pathway?
Cleave C4b
What is the function of Factor H in alternative pathway?
Prevents binding of C3b + Bb => C3bBb
Which 2 regulatory factors other than Factor H that can block binding of C3b & Bb in alternative pathway?
CR1
MCP
What is the function of Factor I in alternative pathway?
Cleave C3b
Why is C4b cleavage by Factor I needed?
Inhibition of C4b are not forever
-> cleaving C4b => C4c + C4d
- -> prevents future accidental activation
What are the 4 regulatory factors after assembly of convertase activity?
C4bBP
CR1
Factor H
DAF ( Decay - accelerating factor )
What is the function of C4bBP, CR1, Factor H & DAF after assembly of C3 convertase?
Dissociates C3 convertase
-> Cleavage of C3b & C4b by Factor I
What are the 3 regulatory factors at assembly of MAC?
S protein
HRF ( Homologous restriction factor )
MIRL ( Membrane inhibitor of reactive lysis )
-> also named CD59
What is the function of S protein?
Prevents insertion of C5b67 into membrane
What is the function of HRF & MIRL?
Prevent assembly of poly C9 to C5b678
What are the 4 complements biological functions?
Lysis
Opsonization
Activation of inflammatory response
Clearance of immune complexes
What is lysis of complements biological function?
MAC ( membrane - attack complex )
-> C5b678 + Poly C9
What is opsonization of complements biological function?
C3b binding on cell
-> phagocytic recognizes C3b
- -> phagocytosis
What is activation of inflammatory response of complements biological function?
Anaphylatoxins
-> C3a, C4a & C5a
- -> Bind to Mast cells receptor ( just like Ag -IgE )
- - -> Induce degranulation
- - - -> Releases Histamine
Chemotactic factors
-> C3a, C5a & C5b67
- -> Induce leukocytes
- - -> Adherence to endothelium
- - - -> Extravasation through endothelium
- - - - -> Migration to site of C’ activation
What is clearance of immune complexes of complements biological function?
Binds to immune complexes ( Ag - Ab )
-> Phagocytosis by phagocytes
-> Binds to CR1 on RBC
- -> Brought to spleen & liver
- - -> Phagocytosis by phagocytes
What happens if clearance of immune complexes fails?
Deposition of immune complexes in tissues
-> Chronic infection
- -> Kidney => Glomerulonephritis
- -> Blood vessel => Arteritis / Vasculitis
- -> Joint => Arthritis
What are the 2 complement receptors?
CR1
CR2
Which of the 3 B cell coreceptor is actually CR2?
CD81
CD21
CD19
CD21
What are 3 categories complement deficiencies?
Congenital deficiency
Decreased production
Increased consumption
What are the 2 congenital deficiency of complement?
Canine C3 deficiency
Porcine Factor H deficiency
What causes decreased production of complement?
Hepatic disease & malfunction
What causes increased consumption of complement?
Immune complexes
CVF ( Cobra venom factor )
-> C3b - like
- -> Lies to Bb </3
- - -> Bangs Bb => forms CVFBb (irreversible)