Lec 7: Innate Inflammatory Responses Flashcards
Anatomical Barriers to Infecton
Physical and chemical barriers
Upon pathogen entry into the host, cellular immune responses, such as IFN and pro-inflammatory cytokine secretion, mediate defense mechanisms.
Antimicrobial compounds secreted
acidic
Physical
Recall: Recognition, progression and resolution
PRR, innate immune response, cellular immunity
recruitment via chemokines
clear out the pathogen
innititate repair
Induction of a anti-pathogen state
1rst and 2nd waves
1rst
PAMP, DAMP (type 1 and type 3), activates PRR, secretes IFN
2nd
Secretion of things like restriction factors
Self-amplifying nature of type I IFN signalling
Lymphoid progenitor plamsacytoid CD cells are teh amin secretors of type I IFNs
IFNs activate antigen presenting cells (ACPs)
IFNs enhance CD8+ T cell cytotoxic activity = more cell debris for DCs
protection of other somatic cells
- > activation of B and macrophages to become antigen presenting cells
- > activate Cyt T cells = more debris for APCs to pick up and cross present antigens
- > protctective tissue responses and type 1 adaptive immune responses
Coordinating innate immune responses **
Interferon (IFNa/b/g)
Think of first and second wave signalling
Triggered by innate responses to infection, damage, or harmful substances
elicits an anti-viral state in infected can surrounding cells
- 1rst wave occurs upon recognition of PAMP/DAMP within infected cell
- 2nd wave results ins secretion of type IFNs - autocrine and paracrine actions
- induction of hundreds of ISGs
autocrine
Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell.
paracrine
Paracrine signaling is a form of cell signaling or cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells.
Coordinating innate immune responses **
pro-inflammatory cytokines
triggered by innate responses to infection, damage, or harmful substances
early components of inflammation include:
- increased vascular permeability (white blood cells can come into the tissue, they are attracted via chemokines
- recruitment of neutrophils and other leukocytes from the blood to the site of damage/ infection
Late components of inflammation include:
tissue remodeling and repair
Inflammation and Tissue Damage
->Role in normal and pathological healing
Activation of innate immune system
- response to DAMPs and PAMPs
- platelets and mast dells degrenulate
- local immune cells are activates - including resident macrophages and DC’s
- recruitment of leukocytes via chemokines - neutrophils first to infiltrate
Steril inflammation
Hypoxic enviroment also promotes inflammation, also tissue damage causes inflammation
What happens after inflammation resolves
there is a period of remodeling and resolution
scarformation and fibrosis may derive from inflammatory cell activity
Fibrosis
Important for the production of dense tissue, and encapsulation of an infection
-> Acts as a bandaide and barrier to prevent more damage
can strengthen tisssue
barrier could lead to loss of function of the organ is// lungs and the brain
Inflammation directs the quality of tissue repair
Inflammatio promotes scar formation
Excessive inflammtion impairs would healing
pro-inflammatory cytokines induce the expression of proteases - unbalanced proteolytic activity can overwhelm tissue protective mechanisms
Chronic inflammation is associated with malignant progression
Excessive inflammation impairs wound healing
low grade chronic inflammation imparis healing due to the expression of proteases.
- matrix
- extracellular proteins
- > loosen everything up
These are all good for the immune system when attacking, but is very bad when prolonged
What is the purpose of Atypical chemokine receptors
they help to buffer and take up excess chemokines
Can you always tell clinically if ther is an inflammatory cascade in your body
nope
What are the clinical presentation of inflammation
Heat and redness = vasodialation
Swelling = increased vascular permeability
Pain = stimulation of nocireceptors
Loss of function = pain, mucsle inhibition, tissue remodeling
Subclinical inflammation can also be present - low grade chronic inflammation
Key pro-inflammatory cytokines
IL-1b
TNF
IL-6
IL-1b
a key pro-inflammatory cytokine
fever producing
involved in degerative diseases
involved in carcinogenesis
little bit of IL-1b is good, chronic low levels = bad
TNFa = TNF
A key pro-inflammatory cytokine
stimulation of HPA axis involved in the acute phase response systemic inflammaiton dysregulation in a variety of dieases chemoattractant and induced phagocytosis, thus, is important in initial responses
acute phase response
response to inflammation
involves fever, increase circulation of neutrophils and and increase in periphery
acute phase proteins =
how the innate immune response can globally talk to immune system via cytokines
Clinical presentaiton = vasodialation and pain
could be nerodegenerative disease
chronic inflammation, with no clinical evidence
needs to cross a threshold in order to become evident
low grade and undiagnosable
also hard to detect because baseline cytokine levels vary widley
Chronic inflammation promoters disease states
Failure to resolve an acute inflammatory state can have severe consequences for the host
-> who ranks chronic disease the greatest threat to human health
can last months to years
What can chronic inflammation result from
failure to eliminate a pathogen
chronic exposure to an irritant*
recurrent episodes of inflammation
autoimmune disease
genetic predispositon*
enviromental and behavioural risk factors
