Host Defence In The Lung: Innate Immunity Flashcards
What is Acute inflammation?
Vasodilatation leads to exudation of plasma, including antibodies
Activation of biochemical cascades, e.g. complement and coagulation cascades
Migration of blood leukocytes into the tissues, mainly neutrophils but also some monocytes
What is inflammation?
Inflammation is our defence against infection and a hostile environment
Many of us will die of diseases caused by inflammatory processes
What is community acquired pneumonia?
- Affects 250,000 adults per annum in UK
- 33% of these admitted to hospital
*Mortality of those admitted is ~10%
What is ARDS?
Respiratory failure
Water and neutrophils fill the alveoli
Multi-system failure
Any condition causing inadequate tissue oxygenation may precipitate ARDS
- commonly trauma, lung infection, sepsis, surgery…
What is the pathology of ARDS?
Endothelial leak – leading to extravasation of protein and fluid
Lungs – reduced compliance, increased shunting
Heart – pulmonary hypertension, reduced cardiac output
Hypoxia
Give examples of diseases that cause inflammation-mediated tissue damage in the lungs
Chronic Obstructive Pulmonary Disease
Acute Respiratory Distress Syndrome
Bronchiectasis
Interstitial Lung Disease
Asthma
What is Acute Inflammation?
Initiated in the tissues, by epithelial production of hydrogen peroxide and release of cellular contents
Amplified by specialist macrophages including:
Kupffer cells (liver)
alveolar macrophages (lung)
histiocytes (skin, bone)
dendritic cells
Respond to pathogens or to tissue injury by recognising:
PAMPs (pathogen-associated molecular patterns)
DAMPs (damage-associated molecular patterns)
How do we recognise pathogens we have never seen before?
Pattern Recognition Receptors (PRRs)
What are the two types of PRRs?
Signalling Toll-like receptors (TLRs)
Nod-like receptors (NLRs)
Endocytic Mannose receptors
Glucan receptors
Scavenger receptors
What are Toll-like receptors?
Funny flies, vulnerable to fungal infections
Mice resistant to endotoxic shock
Recognise conserved molecular patterns in pathogens
TLR4 recognises lipopolysaccharide (LPS)
TLR2 recognises lipotechoic acid (LTA)
Also recognise endogenous mediators of inflammation
What is Alveolar Macrophage?
AM comprise 93% of pulmonary macrophages.
Functionally, cytochemically and morphologically similar to mature tissue macrophages.
Long-lived and arise from monocytes.
What are neutrophils?
70% of all white blood cells
80 million are made each minute, more in sepsis
Turnover 100 million a day
Myeloid cells, related to monocytes and macrophages
Neutrophils are produced in the bone marrow
Participate in the inflammatory response, and protect against infection
Contain GRANULES
PRIMARY – myeloperoxidase, elastase, cathepsins, defensins
SECONDARY – receptors, lysozyme, collagenase
What are functions of the neutrophil?
Identify the threat – receptors
Activation
Adhesion
Migration/chemotaxis
Phagocytosis
Bacterial killing
Apoptosis – programmed cell death
What are the function of neutrophil receptors?
Bacterial structures – cell walls, lipids, peptides
Host mediators – cytokines, complement, lipids
Host opsonins – FcR (immunoglobulin)
CR3 (complement)
Host adhesion molecules
GPCRs – FPRs, BLT1,2, PAFR, C5aR, CXCR1,2, CCR1,2
FC-receptors – 6 gamma, 2 epsilon
Selectin and integrin receptors – 5
Cytokine receptors – Type I, Type II, TNF (20)
Innate immune receptors TLRs(8)
C-type Lecins (5)
NOD-like*
RIG-like* receptors
Explain how neutrophils are used for activation
“Stimulus-response coupling”
Signal transduction pathways involving calcium, protein kinases, phospohlipases, G proteins
