T1 L2 Innate immune defences and inflammation 1

Question 1

How long does the immediate innate immune response take?

Answer 1

0-4 hours

Question 2

How long does the induced innate immune response take?

Answer 2

4h to 4 days

Question 3

Describe the steps of the immediate innate immune response

Answer 3

1) Pathogen invades tissue and proliferates
2) Pathogen is recognised by preformed soluble effector molecules and resident effector cells in infected tissue
3) Pathogen is eliminated, infection ends and minor tissue damage is repaired
OR
Pathogen is not eliminated so proceed with induced innate immune response

Question 4

Describe the steps of the induced innate immune response

Answer 4

1) Pathogen invades tissues and proliferates
2) Activation of cells resident in infected tissue. Recruitment of effector cells to infected tissue.
Inflammation, fever, acute phase response
3) Soluble effector molecules and effector cells recruited to infected tissue recognise and attack pathogen
4) Pathogen is eliminated
OR
Pathogen is not eliminated so proceed with adaptive immune response

Question 5

What type of immunity has its specificity inherited in genome?

Answer 5

Innate

Question 6

What are the differences between innate and adaptive immunity?

Answer 6

Innate triggers immediate response
Innate recognises broad classes of pathogens
Innate interacts with range of molecular structures of given type
Adaptive is encoded in multiple gene segments
Adaptive requires gene rearrangement
Adaptive has clonal distribution
Both are able to discriminate between closely-related molecular structures

Question 7

What are the 3 types of innate barriers to infection?

Answer 7

Physical
Soluble
Induced

Question 8

What are some mechanical barriers to infection?

Answer 8

Epithelial cells joined by tight junctions in the skin, gut, lungs, eyes / nose / oral cavity
Longitudinal flow of air or fluid in skin and gut
Movement of mucus by cilia in lungs
Tears and nasal cilia

Question 9

What are some chemical barriers to infection

Answer 9

Antimicrobial peptides in skin, gut, lungs, eyes / nose / oral cavity
Fatty acids in skin
Low pH and antimicrobial enzymes in gut
Pulmonary surfactant
Antimicrobial enzyme in tears and saliva

Question 10

Describe what happens when tissue is damaged

Answer 10

1) Damage to tissue leads to release of vasoactive and chemotactic factors
2) Triggers local increase in blood flow and capillary permeability
3) Permeable capillaries allow influx of fluid (exudate) and cells
4) Phagocytes migrate to site of inflammation (chemotaxis)
5) Phagocytes and antibacterial exudate destroy bacteria

Question 11

What are some soluble innate immune molecules?

Answer 11

Enzymes e.g. lysozyme
Antimicrobial peptides
Collectins, ficolins and pentraxins
Complement components

Question 12

Where are lysozyme secreted?

Answer 12

By phagocytes and paneth cells from small intestine

Question 13

What do lysozyme do?

Answer 13

Cleave bond between alternating sugars that make up peptidoglycan to disrupt peptidoglycan
Most effective against gram positive bacterial

Question 14

What are antimicrobial peptides secreted by?

Answer 14

Neutrophils
Epithelial cells
Paneth cells in crypts of small intestine

Question 15

Where are histatins produced?

Answer 15

Oral cavity

Question 16

What are histatins active against?

Answer 16

Pathogenic fungi e.g. Candida albicans

Question 17

Describe the structure of defensins

Answer 17

2 classes (alpha and beta)
35-40 aa amphipathic peptides
Disulfide bonds that stabilise structure have a positively charged region separated from hydrophobic region
Disrupt microbial membranes

Question 18

Describe collectins

Answer 18

Globular lectin-like heads that bind bacterial cell surface sugars
Sialic acid hides mannose antigens on the host cells

Question 19

Describe ficolins

Answer 19

Recognise acylated componds

Question 20

Describe pentraxins

Answer 20

Cyclic multimeric proteins found in plasma

Question 21

What are the actions of collectins, ficolins and pentraxins?

Answer 21

Act as opsonins which bind to pathogens and infected cells to target them for phagocytosis
Activate complement through classical / lectin pathway

Question 22

What are complements?

Answer 22

Series of more than 30 proteins that constantly circulate in blood and fluids that bathe the body tissue

Question 23

What are complements made by?

Answer 23

Liver
Monocytes
Macrophages
Epithelial cells of intestine and urinary tract

Question 24

What happens when complements are activated?

Answer 24

Split into small and large fragments which triggers an amplification cascade

Question 25

What are the effects mediated by complement components?

Answer 25

Lysis (membrane attack complex)
Opsonisation
Activation of inflammatory response
Clearance of immune complexes

Question 26

How is the classical pathway initiated?

Answer 26

C1 activation

Question 27

What is C1?

Answer 27

A large molecule of 18 polypeptides that form 6 collagen-like triple helix structures.

Question 28

What 3 proteins make up C1?

Answer 28

C1q
C1r
C1s

Question 29

What protein dominates C1?

Answer 29

C1q

Question 30

Describe the steps of the classical pathway

Answer 30

1) C1 binds to Fc region of antibody antigen complex which activates it
2) Binding C1q with Fc domain leads to conformational change in C1r
3) C1s is cleaved which activates C2 and C4 which split into their large and small fragments
4) C3 converts (C4b2a) activates over 200 C3 molecules causing amplification of the signal
5) C4b, C2a, C3b fragments form C5 converts which activates C5 forming membrane attack complex

Question 31

What activates the lectin pathway?

Answer 31

Ficolins and mannose binding lectin

Question 32

Describe the steps of the lectin pathway

Answer 32

1) Upon binding, MBL forms complex with MASP-1 and MASP-2
2) Active complex cleaves C2 and C4 which split into large and small fragments
3) C3 convertase (C4b2a) activates over 200 C3 molecules causing amplification of signal
4) C4b, C2a, C3b fragments form C5 convertase which activates C5 leading to membrane attack complex.

Question 33

Describe the steps of the alternative pathway

Answer 33

1) C3 spontaneously hydrolyses into C3a and C3b
2) C3b binds to cell membrane and factor B making it susceptible to cleavage by factor D to Bb
3) C3bBb can hydrolyse more C3 leading to more C3b

Question 34

What does the membrane attack complex do?

Answer 34

Forms a pore that inserts into the membrane to allow diffusion of ions and small molecules so water moves into the cell and the cell dies.

Question 35

What is a C1 inhibitor?

Answer 35

Soluble protein that prevents C1 activating C4 and C2.

Question 36

What is hereditary angioedema?

Answer 36

C1 inhibitor deficiency

Means that the classical complement cascade is easily activated

Question 37

How is hereditary angioedema treated?

Answer 37

Injection of C1 inhibitor

Question 38

What is the consequence of have complement deficiencies?

Answer 38

Experience recurrent infections

Question 39

What is the most severe complement deficiency?

Answer 39

C3 deficiency

Question 40

What does MBL deficiency cause?

Answer 40

Serious pyogenic infections in neonates and children

Question 41

What does a C8 deficiency increase the likelihood of?

Answer 41

Infection with Nisseria meningitis

Question 42

Describe systemic lupus erythematous

Answer 42

Autoimmune disease
Occurs in 90% of those deficient for C4
A C4 deficiency means less C3b

Question 43

What happens to C3b that is bound to immune complexes?

Answer 43

Binds CR1 on erythrocytes which transports them to phagocytes in liver and spleen. The phagocytes recognise immune complexes via their Fc receptors and engulf them.