unit 8 - innate immune system

PRRs

the innate immune response has what receptors

PRRs

specificity of the innate immune response

low

response time of innate immune response

quick

memory of innate immune system

none

components of the innate immune response

physical barriers (skin, mucous membrane)

many cells

APCs

diversity/number of receptors in the innate immune response 

7

mechanisms of the innate immune response

• recognise PAMPS (on pathogens)

• recognise DAMPS (on our damaged cells)

receptors of the adaptive immune response

T and B cell receptors

specificity of the adaptive immune response

high

response time of adaptive immunity

slow

why is the adaptive immune response slow

need time to activate Band T cells from APC

memory of adaptive immune response

faster and strong

(b and t cells)

components of adaptive immune response

• lymphocytes (T and B cells)

• antibodies 

• Antigen-presenting cells

diversity/number of receptors of adaptative immune response

millions 

mechanisms of the adaptive immune response

B and T cell receptors recognise specific antigens

INNATE IMMUME SYSTEM

what is the first layer of protection made up of 

• epithelial barriers 

• (skin and mucous membranes) 

• (prevent entry of microbes)

what are the mucous membranes and where

MALT - mucosal membrane

BALT - lungs

GALT - gut

epithelia/skin provides a physical barrier that stops the entry of …

microbes

epithelia/ski produce …..

antibiotic peptides

what are the antibiotic peptides the skin produces

defensins and cathelicidins

what do defensins and cathelicidins do

destruction of pathogens by breaking down the plasma membrane

epithelia/skin harbours …….. that recognise and respond to common microbes 

intraepithelial T lymphocytes 

intraepithelial T lymphocytes are

T memory cells

what are the 4 functions of the innate immune response

1. early defences 

2. tissue repair 

3. cell elimination 

4. activation of adaptive immunity 

early defence - act as the fist line of defence against infections , how fast 

quick response 

tissue repair - participates in

tissue homeostasis and repair

what is involved in tissue homeostasis and repair

M2 macrophages

cell elimination what is eliminated

• damaged cells 

• necrotic cells 

how are necrotic cells and damaged cells removed

phagocytes are involved

macrophages and neutrophils

adaptive immunity activation needs APCS to activate what are the steps 

1. phagocytosis 

2. ingestion 

3. degradation (breaks into smaller pieces)

4. fragments on the surface 

5. B+T cell activation 

what happens after B+T cells are activated

6. proliferation of B+T cells 

7. differentiation of B+T cells

what do B and T cells differentiate into

• Memory T and B cells

• Effector T and B cells 

Effector B cells

plasma membrane - produce antibodies

Effector T cells

TCD4 helper cells

or 

TCD8 cytotoxic  cells

the innate immune system recognises and responds to

PAMPs (pathogens) and DAMPs (damaged cells)

example of PAMPs

peptidoglycan in Gram positive pathogens

example of DAMPs

Cytochrome C

PAMPs are found

plasma membrane of pathogens

PAMPs are present in …… but not in normal host cells

microorganisms

PAMPs are essential for the 

survival and infectivity of microorganisms 

PAMPs and highly or not conserved

highly conserved

highly conserved means

low rate of mutation

DAMPs are molecules expressed or released by

damaged or necrotic cells

DAMPs example is ….. and is in the …

cytochrome C

in the mitochondria membrane 

what happens after DAMPs are released

• signals of damage/infection

• cell death

where do PRRs exist

• membrane bound 

• soluble molecules 

which cells highly express PRRS

• macrophages (phagocyte)

• neutrophils (phagocyte)

• dendric cells 

what is the role of PRRs in phagocytes

trigger phagocytosis when they recognise pathogens

what do PRRs recognise

• PAMPs 

• DAMPs

what is the discrimination ability of PRRs

they differentiate between normal and foreign/damaged cells

what is a TLRs

Toll-like receptor

type of PRR

how many TLRs are there

9

(TLR1 - TLR9)

TLR1,2,4 and 5 are located where

cell surface

TLR1,2,4 and 5 recognise

products of extracellular microbes

TLR3,7,8 and 9 are located 

in endosomes (vesicles) 

what do TLRs recognise

PAMPs

what PAMPs do TLR recognise

1. lipoproteins (surface pathogens) 

2. LPS (lipopolysaccharides)

3. PGN (peptidoglycan)

4. Flagellin 

do TLRs recognise DAMPs

yes

e.g cytochrome C

what is the function of TLR recognition

initiates immune responses by detecting microbial products or cell damage, triggering inflammation and pathogen degradation

what happens after TLR bind to PAMPs or DAMPs

TLRs induce the production of 

1. proinflammatory cytokines 

2. costimulatory molecules (CD80,CD86)

3. type 1 antiviral interferons 

proinflammatory cytokines are

interleukin 1, TNF, IL6

as well as proinflammatory cytokines what are produced

• chemokines

• endothelial adhesion molecules 

what do proinflammatory (IL1, TNF, IL6) chemokines and endothelial adhesion molecules(E-selectin) do

cause inflammation

costimulatory molecules (CD80 and CD86) stimulate

adaptive immunity

where are costimulatory molecules (CD80 and CD86) found

antigen presenting cells 

type 1 antiviral interferons can be

alpha or beta

type 1 antiviral interferons mediate

antiviral defences

if we have a virus what do we need to over express

type 1 antiviral interferons

interfrons are

antiviral compounds

which type of protection does type 1 interferons alpha and beta provide 

• autocrine protection?

• paracrine protection 

• endocrine protection?

autocrine and paracrine 

why not endocrine

needs blood transport

what happens in an infected cell

autocrine process 

1. produces INF 1 

2. secretes INF 1 

3. self recognition of INF 1 

what happens in he paracrine process

an adjacent cell recognises the infected cell

what are NLRs

NOD-like-receptors

where are NLRs located

cytoplasm

what do NLRs detect

PAMPs and DAMPs 

what is the function of NLRs

form signalling complexes that promote acute inflammation

what is NLRP3s role

detect microbial products and cell damage signals

what happens when NLRP3 recognises PAMPs or DAMPs

it undergoes oligomerisation 

what happens during oligomerisation

binds to an adaptor protein and an inactive form of pro-capase-1

what is made when NLRP3 binds to the adaptor protein and the inactive pro-capase-1

inflammasome

what happens after the inflammasome is formed

pro-caspase-1 becomes active (capsase-1)

what does caspase-1 (active) do

synthesis of IL-1 (active) from Pro-IL1 (inactive)

what does an increase in IL-1 do

causes inflammation

what are the steps to form and activate inflammasome

1. detection/sensor (NLRP3 senses PAMPs or DAMPs)

2. assembly (adaptor protein+pro-caspase-1)

3. activation (caspase-1 (active)activates IL-1)

4. inflammation (increase in IL-1 )

what are the 2 other receptors found in the cytoplasm

• RIG-like receptors 

• cytosolic DNA receptors 

location and specificity(what it recognises) of RIG-like receptors 

• cytoplasm 

• viral RNA 

location and specificity(what it recognises) of Cytosolic DNA receptors 

• cytoplasm 

• microbial DNA 

what are the 3 other receptors found in the membrane

• c-type lectin receptors

• CD36/scavenger receptors 

• formyl peptide receptors 

location and specificity(what it recognises) of c-type lectin receptors 

• plasma membrane 

• carbohydrates 

location and specificity(what it recognises) of CD36/scavenger receptors

• plasma membrane

• lipids

location and specificity(what it recognises) of formyl peptide receptors

• plasma membrane

• peptides (proteins)

• pentraxins

• collectins 

• ficolins 

are examples of 

soluble PRRs

what is the consequence of the innate immune system being activated

acute inflammatory response 

dendritic cells and macrophages (APCs) that respond to microbes produce …

cytokines

which cytokines

• IL1

• IL3

• IL6

• TNF-alpha 

dendritic cells and macrophages (APCs) that respond to microbes produce cytokines that stimulate ….

inflammation

dendritic cells and macrophages (APCs) that respond to microbes produce cytokines that stimulate inflammation and active ….

activate NK cells 

dendritic cells and macrophages (APCs) that respond to microbes produce cytokines that stimulate inflammation and active NK cells to produce the  ……..

macrophage-activating cytokine 

NK activation

macrophages release ….. which is recognised by NK cells 

IL-12