- 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)

IAI - innate immune protection Flashcards by Sana Hashemi

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.

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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)

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what are the physical/anatomical barriers of the innate immune system?

skin
GI tract
respiratory tract
mucosal epithelia

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what are the secreted compounds of the innate immune system?

antibacterial compounds
complement
natural antibodies
cytokines

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What are the cellular components of the innate immune system?

phagocytes
NK cells

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what antibacterial compound does the skin produce against e-coli?

psoriasin

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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

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what is the name for the disease when the cilia cant move?

Primary ciliary dyskinesia

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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

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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.

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What 3 barriers prevent pathogen entry?

Physical
Mechanical
Secreted

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How does the innate immune response recognise antigens?

via PAMP:

PAMP = Pathogen Associated Molecular Patterns

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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

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What PAMP is found in gram negative bacteria?

Lipopolysaccharide (LPS) is found in the wall of all gram-negative bacteria.

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What PAMP is found in gram positive bacteria?

Lipoteichoic acid is found in the cell wall of all gram-positive bacteria.

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How does the host recognise these PAMPs?

Pattern Recognition Receptors (PRR).

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what is LPS made from?

A lipid A molecule
and the O polysaccharide.

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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

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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

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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)

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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

1. generation of reactive oxygen intermediates, (more in neutrophils) 2. increase in O2 uptake **respiratory bursts** after phagocytosis 3. O2 reduced by NADPH oxidase = hydroxyl radicals and hypochlorite 4. causes DNA damage and alterations in bacterial membrane

what happens in the killing mechanism, production of reactive nitrogen intermediates, in macrophages and neutrophils

1. **reactive nitrogen intermediates** produced, (more in macrophages) 2. **L-arginine to L-citrulline** generates NO radicals 3. catalysed by enzyme: **inducible nitric oxide synthase** (iNOS, NOS2) induced by cytokines and bacterial components 4. 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?

1. **interleukin 1 (IL-1)** 2. **interleukin 6 (IL-6)** 3. **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)