2.1 Principles of innate immunity to infection Flashcards
Protection of epithelial surfaces (8)
Physical & biochemical barriers: Skin
SKIN:
– Thick layer of cells
– Sebaceous gland secretions
- on surface contain fatty acids
PROBLEMS: pathogens can get into tissue via
– Wounds
– Vector-borne pathogens
(e.g. Lyme disease spread by ticks)
Physical & biochemical barriers: mucous membranes
MUCOUS MEMBRANES:
- Mucociliary escalator, peristalsis
- Coughing and sneezing / Vomiting and diarrhoea
Secretions (saliva, tears and mucous)
• Physical properties (washes away organisms)
• Anti-microbial properties (e.g. lysozyme)
Commensal microflora
commensal bacterial flora (microbiome) :
- is an important defence for mucosal surfaces
- contain friendly bacteria that will die via acid in stomach
Ex: milk
provides the ‘early warning system’ for infection?
Innate immunity
Innate immunity used ___ to detect microbial components that are intrinsically foreign?
Pattern recognition receptors (PRR)
Innate immunity: PAMPs (3)
– Lipopolysaccharide
– Peptidoglycans
– Mannose
Bacteria PAMPs:
- Gram positive
- Gram negative
- Gram positive = peptidoglycan
- Gram negative = lipopolysaccharides
Receptors associated with membrane ?
Toll- like reaceptors
Receptor associated with cytoplasm?
NOD receptors
Recognize gram positive bacteria?
TLR-2
Recognize gram negative bacteria?
TLR-4
Recognize virus nuclei acid?
TLR-3 and TLR-5
What do viruses not have?
Structural PAMPs
How are viruses detected?
Viruses are detected by the presence of dsRNA produced during replication (not found in mammalian cells)
- cells respond by producing interferons
Functions of type 1 interferons:
Resistance to viral replication
– Increased degradation of viral mRNA
– Increased antigen presentation of viral antigens
– Inhibition of viral protein synthesis
Infected cell signaling:
-signals neighboring uninflected cells to destroy RNA and reduce protein synthesis
- Signals neighboring INFECTED cells to undergo apoptosis
- activates immune cells
What type of cells can viruses infect?
Any nuclear cell
All nucleated cells can respond to viral infection by producing ____?
Type 1 interferons
What is interferon omega used to treat?
Persistent viral infection in cats
Ex: FeLV / FIV - won’t cure it but will reduce viral application and burden
Natural killer cells (NK) recognize?
Recognise decreased levels of MHC molecules on host cells
Recognize a symptom of viral infection
– decreased production during viral protein synthesis
– some viruses block transport to cell surface
NK Cell process:
- NK cells monitor cell surface expression of MHC molecules
- NK cells leave healthy cells alone
- in an infected cell, MHC production can be blocked by the virus, this activated NK cell to release cytotoxic granules
- Which kills the infected cell before viral replication is complete
___ is relatively weak to viruses?
Innate immunity
___ is a natural antiviral?
Interferon
- slows viral replication
- makes cells more resistant to infection
___ are able to identify and kill some infected cells (not efficient)
NK cells
_____ keeps you alive till adaptive immunity develops
Innate immunityq
Innate immunity to bacteria
Cellular mechanisms
– Recognition of pathogen
(membrane, vesicular and cytoplasmic PRRs)
– Response: Phagocytosis & inflammation
Humoral mechanisms
– Recognition of pathogen (soluble PRRs)
– Response: Killing of foreign organism,
Enhanced phagocytosis, Inflammation
TTLR-2 recognize
Peptidoglycan
TLR-4 recognize
Lipopolysaccharides
TLR-5 recognize
Flagellin
TLR- 9 recognize
Prokaryotic DNA
NOD2 recognize
Muramyl dipeptide:
- degradation product of peptidoglycan
- present in cytoplasm of wbc
A defect in the NOD2 receptor is responsible for
- Crohn’s disease in humans
- possibly IBD or anal furunculosis
Recognition of bacteria by macrophage TLRs leads to
Phagocytosis and an inflammatory response
What performs phagocytosis?
Neutrophils and macrophages
___ are endocytosed, killed, and digested
Bacteria
Good way to get rid of bacteria ?
Phagocytosis
Respiratory burst:
- enhanced cellular aerobic metabolism
- reactive oxygen intermediates (ROI) are produced
- The oxygen-dependent mechanism of bacterial killing
are cytoplasmic organelles containing defensins, lactoferrin and acid proteases?
Lysosomes - fuse with phagosome, releasing their contents
Lysosomes: defensins
Cationic anti-microbial peptides that damage bacterial cell walls
Lysosomes: lactoferrin
– Binds and chelates free iron, which is required for bacterial growth/replication
Lysosomes: acid proteases
Digestive enzymes active at a low pH
The phago-lysosome becomes increasingly acidic as __ ions are pumped in.
H+ : The acidic environment activates the acid protease enzymes and the micro-organism is digested.
inflammatory mediators:
- histamine
- pro-inflammatory cytokines
- Lipid mediators of inflammation
Histamine is produced by
Mast cells in degranulation in tissues
Pro-inflammatory cytokines are synthesized by
predominantly by white blood cells and macrophages
– e.g. Tumour necrosis factor alpha (TNF-α)
Lipid mediators of inflammation are derived from
arachidonic acid by actions of cyclooxygenases (COX) and lipoxygenases
– e.g. prostaglandins and leukotrienes
Inflammatory cytokines: Localised effects
Vasodilation
– Increased blood flow to tissues (increased heat and redness)
Increased capillary permeability
– increased fluid leakage into tissues - Oedema (increased tissue swelling)
Influx of white blood cells
– Migration of phagocytic cells into tissues
Systemic effects of inflammatory cytokines:
- Hypothalamus
- Liver
- bone marrow
Hypothalamus
– Fever
Liver
– Acute phase response
Bone marrow
– Neutrophil and monocyte mobilization
Humoral (liquid) mechanism of innate immunity
- acute phase proteins
- complement cascade
Acute phase response
Acute phase proteins stick to bacterial cell walls and enhance phagocytosis
Where are complement proteins found?
In the blood
Complement system:
- Series of enzyme activation steps forming an amplification cascade
- small amount of activation is amplified to generate large response
**similar to clotting cascade, but different outcome
Complement system diagram:
Membrane attack complex ( MAC):
is a vital component in the complement cascade
Complement protein C3
Complement protein C3
- C3 is a pro-enzyme
- It is converted to C3a & C3b
Where is C3b deposited?
On the bacterial surface:
– Acts as a marker for recognition by complement receptors on phagocytic cells
– Acts as an enzyme to facilitate the production of the Membrane Attack Complex
C3a:
is released and stimulates an inflammatory response
acts as a target for macrophages & neutrophils stimulating phagocytosis
C3b:
acts as an enzyme to catalyse the formation of the MAC
C3b
stimulates MAST CELL degranulation and triggers an inflammatory response
C3a
Bacteria are attacked by __ and ___
cellular and humoral mechanisms of innate immunity
___ and ___ eat, kill, and digest bacteria
Neutrophils and macrophages
Inflammatory response helps to recruit?
Neutrophils and monocytes to the site of infection
___ and ___ enhance phagocytosis and cause direct lysis
Circulating acute phase proteins and complement proteins
