lecture 4 Flashcards
innate signalling
- process of secreting chemical messages that will help augment the response and cause inflammation, as well as turn on adaptive immunity
what happens if pathogens breach the barriers
- immune cells
what happens after phagocytosis
cytokines and chemokines are released
cytokines
- important immune proteins
- secreted by cells
types of cytokines
- interleukins
- interferuerons
- tumor necrosis factors
- chemokines
complement proteins (important immune protiens
- C3
- it spilts into C3 a and C3 b
- both have rules in immunity
cytokines
- pass the message around to other cells
- target cells that respond to cytokines have specific receptors on them (only way)
- these are NOT PRR receptos
cytokine receptors
- have high affinty
- small quantities of cytokines can turn turn on large bio response
- the response can range
range of responses from cytokines binding to their receptors (correlates immune response)
- changes In expression of target cell
- increase/decerase of enzyme activity
- induce proliferation
- induce differentaion
- modulate effector functions
- cell survival/death
what is another function of cytokines
- cytokines regulate the process of hematopoiesis
-every step of differntiation is guided
every single step is governed by cytokines (different types, expressed by different cells)
hematopoiesis
- gives rise to all types of cells in the blood
- ## starts with hematopoietic stem cell
how do cytokines act?
- another signal transduction process
- ## cytokines act via specific cytokine receptors
signal transduction pathway of cytokines
- inducing stimulus in environment of nucleated cells that have potential of expressing the cytokine
- the signal is transduced into the release of the cytokine
- target cell with cytokine receptor binds to the cytokine,
- turns on or off expression of genes in the cell to produce a biological response.
modes of action of cytokines
- pleiotropy
- redundancy
- cascade induction
pleiotropy
- same cytokine acts on different cells to evoke different responses
redundancy
- different cytokines evoke same response in cels
cascade induction
- action of a cytokine on a cell induces production of one or more additional cytokines.
types of cytokines
- interluekins (IL-6, IL-1)
- tumor necrosis factor (TNF alpha)
interleukins and TNF are pro inflammatory - chemokines
- interferons
whenever pro-inflammatory cytokines are expressed…
- inflammation Is induced
chemokines
- chemoattractant (calls other cells to site of infection the released)
interferons
- Type 1 IFN
- responsible for leading antiviral response
cytokines and phagoyctosis
- PAMPS on pathogen bind to prr
- This triggers phago response
- when pamps bind PRRs, triggers the expression and secretion of cytokines (pro-inflammatory)
(in all of our phagocytes)
chemokines
- ## also secreted by phagocytes
what happens when the barriers of epithelial cells are released
- release of cytokines and chemokines
types of chemokines
- all are secreted
neutrophils and chemokiens
- have receptors to recognize the cheekiness, come out of vessel and follow the signals via chemotaxis to get to site of infection
what types of cells secrete chemokines
- both immune and non-immune
tissue-resident phagocytes
- macrophages, dendritic cells , neutrophils begin to phagocytose, this makes the pro inflammatory cytokines and chemokines
- leads to infllammation
signs of inflammation
- effects of cytokines and inflammatory factors
- dolor (pain
- rubor (redness)
- calor (heat)
- tumor (swelling)
- function lease (loss of - function
why does signs of inflammation happen?
- effects of cytokines in our endothelial cells
effects of cytokines on endothelial cells
- line our blood vessels
- in the presence of cytkoines, the cells expand and the interstitial spaces get bigger
- increased blood flow (readness)
- create leakage of fluid from blood vessels (swelling)
- extravasation of immune cells into tissues (coming out of blood vessels into the tissue to fight infection— creates pain)
process of inflammation
- macrophage phagocytoses bacteria
- produces TNF, Il1 and Il6, this gets released
- chemokines are relased
- cytokines act on endothelial cells
- vasodilation and increased vascular permeability
- inflammatory cels migrate into tissue, releasing inflammatory mediators that cause paun
pus
- made up of mostly neutrophils
- the neutrophils are dying in there
inflammation = considered a positive feedback loop
true
chronic inflammation
- e.g. irritable bowel syndrome caused by chronic inflammation
- increase in infiltrated WBC
- ## disruption of cells structure of epithelia
healthy gut tissue
- led by cytokines
- healthy microbiome in gut
- cytokines are keeping in order
- immune cells are just surveying
disruption of cytokine pathway
- ## inflammation
- more cells coming out of bloodd vessels (redness, swelling)
- leads to ulcers
- not good
- leads to disruption of microbiome
- if left for too long —-> chronic inflammation
- immune system begins to attack own epithelial cells
another response to infection
- fever
why do we get a fever when sick?
- maybe to help control pathogens (difficult to live in high temperatures, but maybe this is not really a big deal)
- enzymes not working as well
- our immune system might work faster at higher temperatures
- it lets us know that we are sick
why fever
- due to inflammatory cytokines
- they travel to hypothalamus
- receptors there cause the fever
- these cytokines are called pyrogens (because they cause fever)
what happens pro-inflammatory cytokines reach the liver
- can also get to liver
- leads to. production and secretion of acute phase proteins
acute phase proteins
- many different ones are produced
- one is c-reactive protein (CRP)
- used in clinical labs to measure for signs of inflammation
Complement system
- helps innate immune system
- many pathways to turn it on
what do complement proteins do?
- help the cells to phagocytose better
- help recruit more cells (act as chemokines, be a message in the tissue)
- form a couple called MAC
Membrane attack complex (MAC)
- a bunch of these proteins polymerizing together, forming holes in the membranes of pathogens to kill them
C3
- broken down into C3A
C3a
- acts as pro-inflammatory cytokine,
calls more cells to infected site, maintains inflammation
C3b
- helps with opsonization (the coating of a surface of a pathogen with antibodies and complement proteins to promote phagocytosis- coating it with a signal to promote phagocytosis)
interferons
- important roles in viral infections
- type 1 interferon
when are IFN alpha and beta released?
- when cells are infected with viruses, these signalling molecules are very quickly released
- ## control viral replication
how are NK cells triggered?
- from the interferon alpha and interferon beta
what happens when NK cells are not enough to eliminate virus
- help of t-cells to control
what happens when viruses are growing in cell
- we have PRRs in cell to recognize the PAMPS that can then turn on the response which is the production of cytokines
signal transduction pathway for virus infected cells
- viral particles are recognized by surface PRRs
- creates signal to turn on expression of interferon
- this is the signal for nK cells to know that they must target the cell
viral survical
- some viruses can block IFN secretion
- this causes cell to not secrete interferons
- this requires T cell immunity to help fight them all
- coronaviruses do this as well
so that they are not attacked by NK cells
