IAI - innate immune protection Flashcards
what is innate immunity?
Innate immunity is a non specific defence mechanism that a host uses immediately or within several hours after exposure to antigen.
describe what happens in 0- 96 hours in innate immunity
0-4 hours = innate immunity (natural immunity)
4-96 hours = Early, induced response
> 96 hours = Acquired immunity (adaptive immunity)
what are the physical/anatomical barriers of the innate immune system?
- skin
- GI tract
- respiratory tract
- mucosal epithelia
what are the secreted compounds of the innate immune system?
- antibacterial compounds
- complement
- natural antibodies
- cytokines
What are the cellular components of the innate immune system?
- phagocytes
- NK cells
what antibacterial compound does the skin produce against e-coli?
psoriasin
How does the respiratory tract prevent entry of pathogens?
- difficult to penetrate due to compact structure and tight cell junctions
- cilia move continuously to move pathogens so they are unable to settle
- mucus traps bacteria to be coughed out or moved with cilia
what is the name for the disease when the cilia cant move?
Primary ciliary dyskinesia
Describe 2 ways that the GI tract provides physical barrier protection?
-
peristalsis movement
wave-like contractions of GI tract to keep bacteria moving -
HCL production + low pH
acidic conditions, activation of acid hydrolyses to destroy bacteria
Describe mechanical and secreted protection in the eyes.
- Blinking occurs first - mechanical
- Then tears - secretion
- Tears, sweat and saliva contain lysozyme which destroys bacteria walls.
What 3 barriers prevent pathogen entry?
- Physical
- Mechanical
- Secreted
How does the innate immune response recognise antigens?
via PAMP:
PAMP = Pathogen Associated Molecular Patterns
What are the two important characteristics for a molecules to be designated a PAMP?
- The PAMP should be present in the microorganism but not the host (so you can differentiate between self and non-self)
- The PAMP must also be essential for the survival of the pathogen
What PAMP is found in gram negative bacteria?
Lipopolysaccharide (LPS) is found in the wall of all gram-negative bacteria.
What PAMP is found in gram positive bacteria?
Lipoteichoic acid is found in the cell wall of all gram-positive bacteria.
How does the host recognise these PAMPs?
Pattern Recognition Receptors (PRR).
what is LPS made from?
- A lipid A molecule
- and the O polysaccharide.
what does the O polysaccharide in LPS tell you?
The O polysaccharide in LPS is the part that tells you what type of gram negative bacteria it is
What are the 3 types of PRRs?
Collectins - soluble receptors that float around in the serum
Toll like receptors (TLRs) - these are membrane bound receptors not only on the cell surface but also on membranes within cells.
Nod like receptors - these sit in the cytoplasm of cells
Describe collectins.
- serum, soluble
- family of proteins present in solution
- Collagen like region and lectin region
- collagen: interacts with effector part of immune system (signal)
- lectin: binds to sugar molecules on surface of pathogen (mannose)
How does TLR3 work?
recognises double stranded RNA
How does TLR5 work?
recognises flagelin
How does TLR9 work?
recognises unmethylated CpG DNA.
What are NOD like receptors?
NOD = Nucleotide Oligomerisation Domain
These sit in the cytoplasm and recognise components of gram-positive and gram-negative bacteria
NOD1 senses
gamma-glutamyl diaminopimelic acid
NOD2 senses
muramyl dipeptide
What are the effector mechanisms of the innate immune response?
- Complement
- Phagocytosis + killing
- Cytokines
- Activation of adaptive immunity
where is complement found and what does it operate by?
series of proteins that circulate in blood and tissue fluids
It operates via a complement cascade - i.e. one product induces the formation of the next.
the key protein in complement is C3 which is activated/ cleaved by?
C3 convertase
What are the three pathways of complement activation?
- The classical pathway
- The alternative pathway
- The mannose-binding lectin pathway
NOTE - even though there are three pathways of complement activation, they all lead to the generation of C3 convertase.
in complement, C3 is split into?
C3a
C3b
whats does C3a do and C3b do?
C3a diffuses away from the site of infection and binds to the C3a receptor on cells such as macrophages and neutrophils (key components of the innate immune response).
The larger component of C3 (C3b) coats pathogens, sits on the surface of pathogens in a process called opsonisation
What does the activation of C5, 6, 7, 8 and 9 do?
C3 also activates the terminal components of complement so C5b, 6, 7, 8 and 9.
These components assemble together to form the MAC - the membrane attack complex.
These components assemble together to make a pore which inserts into bacterial cell walls.
Making a hole into the bacterial cell wall disrupts the osmotic potential and causes bacteria to lyse
What are the 2 main cells in the innate immune response that perform phagocytosis and antimicrobial killing?
Macrophages and neutrophils
where do macrophages mature and where are they found in large numbers.
- Macrophages mature from circulating monocytes in the blood stream
- Found in large numbers in lungs, the liver, the spleen and in the GI tract.
- long lived.
where are neutrophils found and whats its duration
- found only in blood
- short lived
what happens in the killing mechanism, respiratory burst, of macrophages and neutrophils
- generation of reactive oxygen intermediates, (more in neutrophils)
- increase in O2 uptake respiratory bursts after phagocytosis
- O2 reduced by NADPH oxidase = hydroxyl radicals and hypochlorite
- causes DNA damage and alterations in bacterial membrane
what happens in the killing mechanism, production of reactive nitrogen intermediates, in macrophages and neutrophils
- reactive nitrogen intermediates produced, (more in macrophages)
- L-arginine to L-citrulline generates NO radicals
- catalysed by enzyme: inducible nitric oxide synthase (iNOS, NOS2) induced by cytokines and bacterial components
- DNA damage and alternations in bacterial membrane
what is the function of a cytokine?
- proteins
- intercellular messengers
- bind to specific receptors
- activating/deactivating
what 3 things do cytokines activate?
- interleukin 1 (IL-1)
- interleukin 6 (IL-6)
- tumour necrosis factor alpha (TNFA)
what is a chemokine? what does it do?
class of cytokines with chemoattractant properties, it promotes inflammation
chemokines have a particular arrangement of cysteine residues within their structure which classify them into 4 families:
- CXC
- CC
- CX3C
- C
What does it mean for chemokines to be pleotropic?
Unlike cytokines, chemokines can bind to more than 1 receptor and chemokine receptors can bind more than 1 chemokine - they are therefore known as pleotropic.
pleiotropic = 1 chemokine receptor binds to more than one chemokine
what are 2 types of interferons and what do they do
Type 1 interferons: IFNa and IFNb
Type 1 is produced in response to virally infected cells, it also activates another cell that is important in the innate immune response, the natural killer or the NK cells.
Type 2 interferon or interferon gamma - this plays an important part in activating macrophages for antimicrobial killing.
what 2 signals activates the adaptive immune response
MHC and ‘co-stimualtion’
try Keats quiz on innate immune protection
https://keats.kcl.ac.uk/mod/lesson/view.php?id=7651848
What are the two most potent activators of NOS2
interferon gamma and TNF (tumour necrosis factor).
what part of LPS is a pamp?
The PAMP is the lipid A part because the lipid A part is the same in all gram-negative bacteria.
Antigen presenting cells are rich in …
surface class II MHC and costimulatory molecules.
which TLR recognises PAMPS
TLR4
Natural killer cells kill bacteria and viruses in the innate immune response.
is this statement true or false
This statement is false.
NK cells kill infected cells and tumour cells. They do not directly kill bacteria and viruses in the innate immune response.
what are the types of antigen presenting cells, how many are there
3
macrophages
B cells
Dendritic cells (most efficient)
