2.1 Principles of innate immunity to infection

Question 1

Protection of epithelial surfaces (8)

Answer 1

Question 2

Physical & biochemical barriers: Skin

Answer 2

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)

Question 3

Physical & biochemical barriers: mucous membranes

Answer 3

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

Question 4

commensal bacterial flora (microbiome) :

Answer 4

• is an important defence for mucosal surfaces
• contain friendly bacteria that will die via acid in stomach
  Ex: milk

Question 5

provides the ‘early warning system’ for infection?

Answer 5

Innate immunity

Question 6

Innate immunity used ___ to detect microbial components that are intrinsically foreign?

Answer 6

Pattern recognition receptors (PRR)

Question 7

Innate immunity: PAMPs (3)

Answer 7

– Lipopolysaccharide
– Peptidoglycans
– Mannose

Question 8

Bacteria PAMPs:
- Gram positive
- Gram negative

Answer 8

• Gram positive = peptidoglycan
• Gram negative = lipopolysaccharides

Question 9

Receptors associated with membrane ?

Answer 9

Toll- like reaceptors

Question 10

Receptor associated with cytoplasm?

Answer 10

NOD receptors

Question 11

Recognize gram positive bacteria?

Answer 11

TLR-2

Question 12

Recognize gram negative bacteria?

Answer 12

TLR-4

Question 13

Recognize virus nuclei acid?

Answer 13

TLR-3 and TLR-5

Question 14

What do viruses not have?

Answer 14

Structural PAMPs

Question 15

How are viruses detected?

Answer 15

Viruses are detected by the presence of dsRNA produced during replication (not found in mammalian cells)

• cells respond by producing interferons

Question 16

Functions of type 1 interferons:

Answer 16

Resistance to viral replication
– Increased degradation of viral mRNA
– Increased antigen presentation of viral antigens
– Inhibition of viral protein synthesis

Question 17

Infected cell signaling:

Answer 17

-signals neighboring uninflected cells to destroy RNA and reduce protein synthesis
- Signals neighboring INFECTED cells to undergo apoptosis
- activates immune cells

Question 18

What type of cells can viruses infect?

Answer 18

Any nuclear cell

Question 19

All nucleated cells can respond to viral infection by producing ____?

Answer 19

Type 1 interferons

Question 20

What is interferon omega used to treat?

Answer 20

Persistent viral infection in cats
Ex: FeLV / FIV - won’t cure it but will reduce viral application and burden

Question 21

Natural killer cells (NK) recognize?

Answer 21

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

Question 22

NK Cell process:

Answer 22

1. NK cells monitor cell surface expression of MHC molecules
2. NK cells leave healthy cells alone
3. in an infected cell, MHC production can be blocked by the virus, this activated NK cell to release cytotoxic granules
4. Which kills the infected cell before viral replication is complete

Question 23

___ is relatively weak to viruses?

Answer 23

Innate immunity

Question 24

___ is a natural antiviral?

Answer 24

Interferon
- slows viral replication
- makes cells more resistant to infection

Question 25

___ are able to identify and kill some infected cells (not efficient)

Answer 25

NK cells

Question 26

_____ keeps you alive till adaptive immunity develops

Answer 26

Innate immunityq

Question 27

Innate immunity to bacteria

Answer 27

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

Question 28

TTLR-2 recognize

Answer 28

Peptidoglycan

Question 29

TLR-4 recognize

Answer 29

Lipopolysaccharides

Question 30

TLR-5 recognize

Answer 30

Flagellin

Question 31

TLR- 9 recognize

Answer 31

Prokaryotic DNA

Question 32

NOD2 recognize

Answer 32

Muramyl dipeptide: - degradation product of peptidoglycan - present in cytoplasm of wbc

Question 33

A defect in the NOD2 receptor is responsible for

Answer 33

- Crohn’s disease in humans - possibly IBD or anal furunculosis

Question 34

Recognition of bacteria by macrophage TLRs leads to

Answer 34

Phagocytosis and an inflammatory response

Question 35

What performs phagocytosis?

Answer 35

Neutrophils and macrophages

Question 36

___ are endocytosed, killed, and digested

Answer 36

Bacteria

Question 37

Good way to get rid of bacteria ?

Answer 37

Phagocytosis

Question 38

Respiratory burst:

Answer 38

- enhanced cellular aerobic metabolism - reactive oxygen intermediates (ROI) are produced - The oxygen-dependent mechanism of bacterial killing

Question 39

are cytoplasmic organelles containing defensins, lactoferrin and acid proteases?

Answer 39

Lysosomes - fuse with phagosome, releasing their contents

Question 40

Lysosomes: defensins

Answer 40

Cationic anti-microbial peptides that damage bacterial cell walls

Question 41

Lysosomes: lactoferrin

Answer 41

– Binds and chelates free iron, which is required for bacterial growth/replication

Question 42

Lysosomes: acid proteases

Answer 42

Digestive enzymes active at a low pH

Question 43

The phago-lysosome becomes increasingly acidic as __ ions are pumped in.

Answer 43

H+ : The acidic environment activates the acid protease enzymes and the micro-organism is digested.

Question 44

inflammatory mediators:

Answer 44

- histamine - pro-inflammatory cytokines - Lipid mediators of inflammation

Question 45

Histamine is produced by

Answer 45

Mast cells in degranulation in tissues

Question 46

Pro-inflammatory cytokines are synthesized by

Answer 46

predominantly by white blood cells and macrophages – e.g. Tumour necrosis factor alpha (TNF-α)

Question 47

Lipid mediators of inflammation are derived from

Answer 47

arachidonic acid by actions of cyclooxygenases (COX) and lipoxygenases – e.g. prostaglandins and leukotrienes

Question 48

Inflammatory cytokines: Localised effects

Answer 48

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

Question 49

Systemic effects of inflammatory cytokines: - Hypothalamus - Liver - bone marrow

Answer 49

Hypothalamus – Fever Liver – Acute phase response Bone marrow – Neutrophil and monocyte mobilization

Question 50

Humoral (liquid) mechanism of innate immunity

Answer 50

- acute phase proteins - complement cascade

Question 51

Acute phase response

Answer 51

Acute phase proteins stick to bacterial cell walls and enhance phagocytosis

Question 52

Where are complement proteins found?

Answer 52

In the blood

Question 53

Complement system:

Answer 53

- 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

Question 54

Complement system diagram:

Answer 54

Question 55

Membrane attack complex ( MAC):

Answer 55

Question 56

is a vital component in the complement cascade

Answer 56

Complement protein C3

Question 57

Complement protein C3

Answer 57

- C3 is a pro-enzyme - It is converted to C3a & C3b

Question 58

Where is C3b deposited?

Answer 58

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

Question 59

C3a:

Answer 59

is released and stimulates an inflammatory response

Question 60

acts as a target for macrophages & neutrophils stimulating phagocytosis

Answer 60

C3b:

Question 61

acts as an enzyme to catalyse the formation of the MAC

Answer 61

C3b

Question 62

stimulates MAST CELL degranulation and triggers an inflammatory response

Answer 62

C3a

Question 63

Bacteria are attacked by __ and ___

Answer 63

cellular and humoral mechanisms of innate immunity

Question 64

___ and ___ eat, kill, and digest bacteria

Answer 64

Neutrophils and macrophages

Question 65

Inflammatory response helps to recruit?

Answer 65

Neutrophils and monocytes to the site of infection

Question 66

___ and ___ enhance phagocytosis and cause direct lysis

Answer 66

Circulating acute phase proteins and complement proteins