Innate immune system

Question 1

What are some of the key physical barriers comprising the innate immune system?

Answer 1

• Eyelids protect the eye
• Mucous and cilia in the airways
• Ear wax contains anti-microbials
• Tears and saliva contain antimicrobials and lysozymes

Question 2

How is the innate immune system present in the gut?

Answer 2

• Low pH (not conducive to the growth of certain bacteria)
• Contains mucous and a microbiome
• Proteases (could attack viral proteins HA and NA)

Question 3

What species do not have lysozymes in their tears?

Answer 3

Cattle

Question 4

What is a lysozyme?

Answer 4

An enzyme that attacks peptidoglycan in the cell wall of gram +ve bacteria.

Question 5

Defensins are another form of anti-microbial, what are they?

Answer 5

• Defensins are small, positively charged proteins effective against viruses (particularly enveloped ones), bacteria and fungi
• Present in the lungs, skin, gut and tears
• Causes pores in the phospholipid bilayer.

Question 6

How does the innate immune system recognise pathogens?

Answer 6

• Innate cells recognise non-self molecules using pattern recognition receptors
• PRRs recognise PAMPs

Question 7

Name some examples of non-self molecules.

Answer 7

• LPS, double stranded RNA, flagella

Question 8

What are the 4 different types of pattern recognition receptor?

Answer 8

• TLR
• NOB-like receptors
• Lectins
• RIG-like receptors

Question 9

What are the functions of TLR4 and TLR9?

Answer 9

• TLR4 recognises LPS on gram -ve bacteria
• TLR9 recognises Cp6 DNA (can be viral or bacterial)

Question 10

Where can TLRs be found on innate immune cells?

Answer 10

• Some TLRs occur on the cell surface
• Some TLRs occur within endosomes and are used to recognise nucleic acid structures.

Question 11

How are pattern recognition receptors activated?

Answer 11

• TLRs dimerize and induce signalling via adapter proteins (TRIF or Myd88)
• TLR initiated signalling activated transcription factors

Question 12

What is the purpose of these transcription factors?

Answer 12

They mediate the transcription of specific cytokines, such as interferons

Question 13

When are interferons important?

Answer 13

In an early anti-viral response

Question 14

What are the 2 different types of interferon?

Answer 14

Alpha IFN
Beta IFN

Question 15

Where are interferons produced?

Answer 15

Produced by virally infected cells (within hours of infection)

Question 16

How do interferons lead to the production of anti-viral components?

Answer 16

• They cause inhibition of viral protein translation and block the assembly of viral nucleocapsids
• Cause degradation of dsRNA
• Upregulate MHC class 1 - a molecule presented on the surface of viral infected body cells to help alert the immune system
• Work in a paracrine way

Question 17

Why are German Shepherds more susceptible to inflammatory bowel disease?

Answer 17

• Because they have polymorphisms in TLR 4 and TLR 5 genes
• Ineffective bacterial detection so risk of disease increases

Question 18

In what 4 ways does the innate immune system work to kill pathogens? What is it responsible for each pathway?

Answer 18

• Inflammation (acute phase proteins)
• Phagocytosis (macrophages and neutrophils)
• Netosis (neutrophils)
• Killing infected host cells (NK cells)

Question 19

What are the symptoms of acute inflammation?

Answer 19

• Swelling and redness
• Heat and fever
• Pain
• Loss of function

Question 20

When is the inflammatory response seen in the absense of infectious disease?

Answer 20

With injury or arthritis

Question 21

What are the 3 types of cytokines released during inflammation?

Answer 21

TNF alpha
IL - 1
IL - 6

Question 22

What are the 4 other mediators released during inflammation?

Answer 22

• Histamine
• Chemokines
• Prostaglandins
• Leukotrienes

Question 23

What 2 substances specifically cause redness and heat?

Answer 23

• IL-1 and TNF alpha
• These lead to vasodilation and increased vascular permeability
• Capillaries come closer to the surface

Question 24

Which substances cause swelling - how?

Answer 24

• Chemokines
• Cause cellular infiltration at the site of infection + upregulation of adhesion molecules on endothelium

Question 25

What are the 3 acute phase proteins released from the liver into the blood?

Answer 25

Mannan-binding lectin C-reactive protein Complement

Question 26

What is the function of all of these acute proteins?

Answer 26

To contribute to opsonisation and thus aid phagocytosis

Question 27

What is opsonisation?

Answer 27

The coating of a pathogen surface in specific proteins to aid recognition and phagocytosis.

Question 28

What are C3a, C4a, and C5a proteins responsible for?

Answer 28

C3a = mast cell activation/degranulation C4a = mast cell activation C5a = chemotaxis, vasodilation, neutrophil and mast cell activation/ degranulation.

Question 28

What happens when a bacterium is coated with C3b proteins?

Answer 28

- C3b proteins bind to CR1 receptors on a macrophage - C5a proteins must bind to C5a receptor on the macrophage and initiate phagocytosis.

Question 29

What is the destruction complement function?

Answer 29

Polymerisation of terminal proteins forms membrane attack complexes - These form pores in the cell membrane and can cause cell lysis

Question 30

What happens during phagocytosis?

Answer 30

- PRRs and other receptors bind to the pathogen - Transported by phagosomes - Phagosome fuses with lysosome - Pathogen destroyed by lysosome products

Question 31

What is the definition of immune evasion? How does this work?

Answer 31

Definition = the deliberate moderation of a host immune system to benefit the infectious agent How work = 1) Can prevent phagocytosis 2) Can prevent lysosome fusion 3) Can cause pathogen to escape the endosome.

Question 32

What are the two key phagocytic cells during inflammation?

Answer 32

Macrophages and neutrophils

Question 33

What is the additional function of the macrophages?

Answer 33

- Release specific cytokines and chemokines - This helps to attract other innate and adaptive immune cells to the site

Question 34

How does a bacterial infection cause inflammation?

Answer 34

- Bacteria triggers macrophages to release cytokines and chemokines - Vasodilation and increased vascular permeability causes redness, heat and swelling - Inflammatory cells migrate into the tissue and release inflammatory mediators.

Question 35

What is the function of neutrophils?

Answer 35

- Kill extracellular bacteria + fungi after activation - Release antimicrobial nuclear contents

Question 36

What is netosis?

Answer 36

When neutrophils release extracellular traps (nets) which cause cell death (not apoptosis)

Question 37

How do natural killer cells distinguish infected from non-infected cells?

Answer 37

By MHC class 1 interactions

Question 38

How is it that NK cells do not kill normal, healthy cells?

Answer 38

MHC class 1 on normal cell regognised by inhibitory receptors that inhibit signals from activating receptors

Question 39

How do NK cells destroy infected cells?

Answer 39

- Altered or absent MHC class 1 cannot stimulate the negative signal - NK cell triggered by signals from activating receptors - Activated NK cell releases granule contents (causes apoptosis)