Lec 7: Innate Inflammatory Responses Flashcards Preview

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Flashcards in Lec 7: Innate Inflammatory Responses Deck (47)
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1
Q

Anatomical Barriers to Infecton

A

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

2
Q

Recall: Recognition, progression and resolution

A

PRR, innate immune response, cellular immunity

recruitment via chemokines
clear out the pathogen
innititate repair

3
Q

Induction of a anti-pathogen state

1rst and 2nd waves

A

1rst
PAMP, DAMP (type 1 and type 3), activates PRR, secretes IFN

2nd
Secretion of things like restriction factors

4
Q

Self-amplifying nature of type I IFN signalling

A

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
5
Q

Coordinating innate immune responses **

Interferon (IFNa/b/g)

Think of first and second wave signalling

A

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
6
Q

autocrine

A

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.

7
Q

paracrine

A

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.

8
Q

Coordinating innate immune responses **

pro-inflammatory cytokines

A

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

9
Q

Inflammation and Tissue Damage

->Role in normal and pathological healing

A

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
10
Q

Steril inflammation

A

Hypoxic enviroment also promotes inflammation, also tissue damage causes inflammation

11
Q

What happens after inflammation resolves

A

there is a period of remodeling and resolution

scarformation and fibrosis may derive from inflammatory cell activity

12
Q

Fibrosis

A

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

13
Q

Inflammation directs the quality of tissue repair

A

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

14
Q

Excessive inflammation impairs wound healing

A

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

15
Q

What is the purpose of Atypical chemokine receptors

A

they help to buffer and take up excess chemokines

16
Q

Can you always tell clinically if ther is an inflammatory cascade in your body

A

nope

17
Q

What are the clinical presentation of inflammation

A

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

18
Q

Key pro-inflammatory cytokines

A

IL-1b

TNF

IL-6

19
Q

IL-1b

A

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

20
Q

TNFa = TNF

A

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
21
Q

acute phase response

A

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

22
Q

Clinical presentaiton = vasodialation and pain

A

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

23
Q

Chronic inflammation promoters disease states

A

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

24
Q

What can chronic inflammation result from

A

failure to eliminate a pathogen

chronic exposure to an irritant*

recurrent episodes of inflammation

autoimmune disease

genetic predispositon*

enviromental and behavioural risk factors

25
Q

what do activated macrophages secrete after classical activation

A

Macrophages are tissue resident immune cells
Derived from circulating monocytes that migrate into tissues

“classical activation” = pro-inflammatory
-> secretion of cytokines (IL-1, IL-6, TNFa) and chemokines and mediators such as inducible NO synthase (iNOS)

26
Q

Alternative activated states of macrophages

A

Can transition from pro-inflammatory to “alternatively activates” states

-> secretion of anti-inflammatory IL-10 and growth factors like TGFb, VEGF and IGF-1

Acternatively activates = modulation of functional nd signalling

  • > resolution of inflammation and growth factors for wound repair
  • > extracellular matric synthases
27
Q

How to macropahges help in the clean up process, after inflammation

A

are cruical for removal of neutrophils in a wound

promote angiogenesis, fibroblast proliferation and ECM synthesis (extracellular matrix)

28
Q

Angiogenesis

A

new blood vessel formation from pre-existing vessles

29
Q

What are the phenotypes of macrophages

A

M1

M2

30
Q

M1 phenotype

A

macropahge

inflammatory and first to site of tissue injury

31
Q

M2 phenotype

A

macrophage

anti-inflammatory and promotes tissue repair after the infection has passed

32
Q

What happens if there is a failure in the transition from the M1 phenotype to the M2 Phenotype

A

diease states, chronic inflammaiton

33
Q

+ve feedback for regualation of the innate and inflammatory response

A

?

34
Q

-ve feedback for regualation of the innate and inflammatory response

A

?

35
Q

+ve feedback

A

effects increase the magnatute of the system

36
Q

-ve feedback

A

reduces the overall magantuse of the system

37
Q

Regulation of innate and inflammatory responses

A

regulations and control of these responses are important for ensurig minimum collateral damage to the host

Defects in PRRss and Signaling pathways increase susceptibility to infections

Defects that allow the systems to remain abnormally “turned on” contribute to inflammatory systesm

Regulation includes both **

  • positive feedback mechanisms (amplification fo response)
  • Negative feedback mechanisms (termination of response)
38
Q

How do dendritic cells bridge both arms of the immune system

A

They are founs in most tissue and are abundant at interfaces between external and internal enviroments

DCs express numerous PRRs and cytokine receptors: highly responsive to DAMPS and PAMPS, as well as inflammatory signalling

Signal to the adaptive immune system that there is an ongoing innate immune response

Tissue resident DC’s migrate to drainign lymph nodes

Direct T cells how to respond to the situation

39
Q

Interactions between the innate and adaptive immune systems

A

A constant interplay between the two systems exists

DCs are a key bridge

DCs can drive strong innate immune responses

DCs direct the coordinated activation of the adaptive arm

40
Q

Name some innat immune signalling PRRs and DCs?

A

???

41
Q

Treg

A

=imune supression = Th2 helper cell
suppression against a given antigen

activated by TLR2/1 -> IL-10 -> Treg

42
Q

What is the purpose of inflammation

A

?

43
Q

What are the clinical hallmarks of inflammation, and can you determine it?

A

?

44
Q

Whate are the biological and clinical effects of the following cytokines:

IL-1b
TNFa
IL-6

A

IL-1b is secreated by monocytes, macrpohages, DCs NK cells and epithileal as well as endothelial cells. It causes the induction of a local inflammaotry response, feaver, acute pahse response and timulation of neturophil production.

TNFa is secreated by monocytes, macrophages as well as activated T cells, NK cells neutrophiles and fibroblasts. They are strong mediators of the inflammatory and immune funcitons. Cytoxic responses for non and transformed cells and also promotes angiogenesis.

IL-6B is secreated by some T and B cells and several non-lymphophoid cells including macrophages. It regulates T and B cell functions and induces inflammation and the acutre phase response.

45
Q

Explain how inflammation impacts tissue repair processes. Give an example.

A

?

46
Q

How is innate immunity and inflammation tied to adaptive immunity?

A

?

47
Q

Pathogen induced inflammation

A

In some cases allows a specific pathogen to spread

Recruitment of a cell that it is trophic to towards the microbe
=disseminatnion = hitchhiking