T1 L2: Innate immune defences & inflammation 1

Question 1

What is innate immunity?

Answer 1

The first line of defence against infection which is present from birth and is passed down genetically

It occurs within minutes of pathogen recognition

Question 2

What are some receptor characteristics of innate immunity?

Answer 2

• Specificity is inherited
• It expressed by all cells of a particular type
• It triggers an immediate response
• It recognises a broad class of pathogens
• Interacts with a range of molecular structures of a given type
• Able to discriminate between closely related molecular structures

Question 3

What are some characteristics of adaptive immunity?

Answer 3

• Encoded in multiple gene segments
• Requires gene rearrangement
• Clonal distribution
• Able to discriminate between closely related molecular structures

Question 4

What is trained immunity?

Answer 4

Innate immune memory

Cells respond differently the second time because of epigenetic and metabolic reprogramming

It lasts for weeks of months because the training occurs in haemopoietic stem cells of bone marrow

Question 5

What are some physical innate barriers to infection?

Answer 5

Skin
Respiratory tract
GI tract

Question 6

What are some soluble innate barriers to infection?

Answer 6

Complement
Defensins
Collectins

Question 7

What are some induced innate barriers to infection?

Answer 7

• Innate immune cells
• Pattern recognition receptors (PPR’s)
• Interferons

Question 8

What is the function of lysozymes?

Answer 8

They disrupt bacterial cell walls by acting on peptidoglycans

Found in blood and tears

Question 9

What is the function of antimicrobial peptides?

Answer 9

They kill pathogens by disrupting microbial membranes

Found pretty much everywhere

Question 10

Which molecules bind to pathogens and target them for phagocytosis and to activate compliment?

Answer 10

Collectins, ficolins, and pentraxins

They act as opsonins by activating the complement pathway.

Question 11

Where are lysozymes secreted?

Answer 11

By phagocytes and Paneth cells from the small intestine

Question 12

Describe the process by which lysozymes disrupt the cell wall

Answer 12

They cleave the bonds between alternating sugars that make up peptidoglycan. Then phospholipase A2 comes and disrupts the phospholipids underneath

Question 13

Which type of bacteria have exposed peptidoglycan layers?

Answer 13

Gram-positive bacteria

Question 14

What are histatins?

Answer 14

A type of antimicrobial peptide

They are produced by the oral cavity and are active against pathogenic fungi like candida albicans

Question 15

What are Cathelicidins?

Answer 15

A type of antimicrobial peptide

Humans only have LL-37 which has broad spectrum activity against both gram-negative and gram-positive bacteria

Question 16

What are defencins?

Answer 16

They are amphipathic peptides that insert themselves into the cell membrane and create a pore

They have two classes: alpha and beta

Question 17

What are the 3 main types of antimicrobial peptides?

Answer 17

Histatins, Cathelicidins, and Defensins

Question 18

What are some characteristics of antimicrobial peptides?

Answer 18

• They are secreted by neutrophils, epithelial cells, and Paneth cells in the crypts of the intestine
• Kill bacteria in minutes
• Attack fungi and viruses and kill them by inhibiting DNA and RNA synthesis

Question 19

What does amphipathic mean?

Answer 19

Hydrophilic on one side and hydrophobic on the other

Question 20

How do collectins work?

Answer 20

They have globular lectin-like heads that bind to bacterial cell surface sugars

Sialic acid hides mannose antigens on host cells

Question 21

How do Ficolins work?

Answer 21

They have a fibrinogen-like domain that recognises acylated compounds (COCH3) such as bacterial cell wall monosaccharides

Question 22

How do Pentraxins work?

Answer 22

They are multimeric proteins in the plasma that bind to Fc gamma receptors to opsonise the pathogen

Eg. C-reactive protein (CRP). It binds to phosphocholine on bacterial surfaces. It’s used as a marker for inflammation

Question 23

What are the 3 pathways to complement?

Answer 23

Classical, lectin, and alternative pathway

Question 24

Describe the classical pathway of complement

Answer 24

Antigen-antibody complexes form of the pathogen surface. Molecules like C1q, C1r, C1s, C4, and C2 are created

C2 and C4 come together to cleave C3 causing amplification

Question 25

Describe the lectin pathway of complement

Answer 25

Mannose-binding lectin or ficolin binds to carbohydrates on pathogen surfaces and molecules like MBL/ficolin, MASP-2, C4, and C2 are released

C2 and C4 then cleave C3 to cause amplification

Question 26

Describe the alternative pathway of complement

Answer 26

Activated by pathogen surfaces to release molecules like C3, B, and D

Activated by C3 in the blood which can spontaneously become C3a and C3b but is very unstable

C3bBb hydrolyses C3 creating more C3b which amplifies the signal

Question 27

How do all 3 complement pathway converge?

Answer 27

The products of each pathway are converted into C3

Question 28

In what form do complement components circulate in the blood?

Answer 28

As pro- innactive forms

Question 29

Which compound initiates the classical pathway of complement?

Answer 29

Activation of C1 when it binds to the Fc region

It’s made up of 3 proteins: C1q, C1s, and C1r

Question 30

Why is IgM the most effective at activating complement?

Answer 30

Because complement is triggered by binding to Fc regions and IgM has 5

At least 2 are needed

Question 31

What is the function of properdin?

Answer 31

It extends the half-life of C3bBb from 5 min to 30 min by protecting it from proteases

This allows more amplification of the alternative pathway

Question 32

What is a membrane attack complex (MAC)?

Answer 32

It’s a ring of C9 molecules created once C5 is cleaved. It’s the end product of complement.

It creates a pore when it inserts itself into a cell membrane

Human cells have proteins that prevent MAC formation

Question 33

What is hereditary angioedema?

Answer 33

A C1 inhibitor deficiency that causes the classical complement cascade to be easily activated

It can be treated with C1 inhibitor injections

Question 34

What does a mannose-binding lectin (MBL) deficiency cause?

Answer 34

Serious pyogenic infections in neonates and children

Question 35

What does pyogenic mean?

Answer 35

A pus-producing infection

Question 36

What does a C3 deficiency cause?

Answer 36

The most severe complement deficiency leading to successive severe infections

Question 37

What does a C8 deficiency cause?

Answer 37

These patients are prone to infections with Neisseria meningitis

Question 38

What does a C4 deficiency cause?

Answer 38

90% of these people go on to develop the autoimmune disease systemic lupus erythematosus (SLE)

Question 39

What is systemic lupus erythematosus (SLE)?

Answer 39

The person have lots of autoantibodies that cause excessive inflammation

It’s caused by a C4 deficiency because that means less C3b is cleaved

Question 40

What is the function of C3b?

Answer 40

Opsonisation

It binds to immune complexes and then CR1 on erythrocytes which transport them to phagocytes in the liver and spleen.

Phagocytes recognise them via their Fc receptors and engulf them