Innate immunity 1

Question 1

Key characteristics of the innate immune system [6]

Answer 1

Genome encoded

Some receptors are expressed by all cells of a cell type
- Like in macrophages.

Immediate response.

Not specific to antigens.
-	Recognizes broad class of antigens using PRRs.

Interacts with a range of molecular structures of a given type.

Able to discriminate between closely related molecular structures.
- As seen with MBL.

Question 2

Mechanical anatomical barriers against pathogens [4]

Answer 2

Tight junctions in epithelial cells: skin, gut, eyes, nose, mouth, lungs.

Longitudinal flow of air/fluid: gut, skin.

Movement of mucus by cilia: lungs.

Tears and nasal cilia: eyes, nose, mouth.

Question 3

Chemical anatomical barriers against pathogens [5]

Answer 3

All structures: antimicrobial peptides.

Skin: Fatty acids

Gut: Low pH, antimicrobial peptides.

Lungs: Pulmonary surfactant containing collectins.

Eyes, nose, mouth: Antimicrobial enzymes in tears and saliva.

Question 4

Microbiological anatomical barriers against pathogens

Answer 4

Normal microbiota in all structures (skin, lungs, eyes, nose, gut, mouth)

Question 5

Pentraxins

Answer 5

Soluble molecule- cyclic multimeric protein

Binds to pathogens, tags for phagocytosis.

Question 6

Lysoszyme

Answer 6

Antimicrobial enzyme

• Found in tears, saliva
• Dirupts bacterial cells walls

Question 7

Phospholipase A2

Answer 7

Secretory form acts as antimicrobial enzyme

• Found in the blood
• Disrupts bacterial cell wall

Question 8

Antimicrobial peptides [4]

Answer 8

Amino acid chains secreted by neutrophils, paneth cells (small intestines)
- Cover epithelial surfaces, found in saliva.

• Disrupts bacterial membrane.
• Attacks fungi and viruses.
• Inhibits RNA and DNA synthesis.

Question 9

Histatins

Answer 9

Antimicrobial peptide

• Produced in oral cavity
• Attacks fungi, like c. abicans

Question 10

Defensins

Answer 10

Amphipathic, antimicrobial peptide that disrupt microbial cell membranes by forming a pore in plasma membrane
- Does not attack host cells

Structure

• 35-40 a.a
• Disulphide bonds to stabilise structure

Question 11

Collectins

Answer 11

Pattern recognition receptor

• Lectin head binds to sugars on bacterial surface
• Collagen tail binds to phagocytes

Example: MBL, activates complement cascade
- Host cells are protected via sialic acid covering mannose

Question 12

Ficolins

Answer 12

Trimer molecule that recognises acylated compounds on bacterial cell wall
- Collagen and fibrinogen domain

• Activates complement
• Carries out opsonisation

Question 13

Action of ficolins, collectins and pentaxins.

Answer 13

Act as soluble PRR

Opsonisation of infected cells for phagocytosis

Activation of the classical/ lectin complement pathway.

Question 14

Classical component pathway

- Activation

Answer 14

Activated by Ag-Ab complex binding to C1q on C1qC1rC1s.
- IgM is usually the antigen, and at least 2 Fc domain bound to C1q.

IgM can only bind in staple form, not planar
- Staple form occurs when bound to Ag.

Activated C1q cleaves C14.

Question 15

Classical component pathway

- Amplification

Answer 15

Activated C1r cleaves C1s
- C1s cleaves C2 and C4

C2a and C4b form C3 convertase
- Cleaves C3 into C3a, C3b.

C3b, C2a, C4b combine to form C5 convertase
- Cleaves C5, forms membrane attack complex (MAC)

Question 16

Lectin component pathway

- Activation

Answer 16

Activated by MBL or ficolin bound to pathogen

- MBL forms complex with MASP1, 2.

Question 17

Lectin component pathway

- Amplification

Answer 17

MBL-MASP1/2 complex cleaves C2, C4

- Forms C3/5 convertase leaving to C3b and MAC production downstream

Question 18

Alternative component pathway

- Activation

Answer 18

Pathogenic surface comes into contact with C3

- Spontaneous lysis into 3a, 3b.

Question 19

Alternative component pathway

- Amplification

Answer 19

C3b binds to cell membrane/ factor B
- Cleaves Factor D into Bb.

C3bBb can cleave C3, making more C3b

C3bBb only has a half life of 5 mins
- Prolonged by the release of properdin from leucocytes during inflammation.

Question 20

C3a, C5a function

Answer 20

Peptide mediator of inflammation

Recruits phagocytes

Question 21

C3b function

Answer 21

Opsonisation

- Binds to complement receptor on phagocyte- facilitate phagocytosis to remove immune complexes

Question 22

MAC

Answer 22

Membrane attack complex
- Formed from the activation form C6 by C5b—> cascade to from C5b6789

MAC forms pores in cell membrane
- Influx of water, ions, sugar= cell lysis

Host cells protected against MACs via soluble and cell surface proteins

Question 23

Hereditary angioedema

Answer 23

Caused by C1 inhibitor deficiency
- Leads to easy activation of Classical complement cascade

Symptoms
- Swelling in hands, face, feet and airway

Question 24

MBL deficiency

Answer 24

Inhibits Lectin complement pathway
- Leads to severe pyogenic infections in children and neonates

Eventually recovers with age due to compensation from adaptive immune system

Question 25

C3 deficiency

Answer 25

Prevents the formation of C3b in all complement pathways

- Most severe due to the important role of C3b (cannot opsonise bacteria)

Question 26

C8 deficiency

Answer 26

Associated with being prone to meningitis infection (Neissera)

Question 27

SLE and complements

Answer 27

90% of those with C4 deficiency develop SLE
- Inability to make C3 convertase, hence C3b

C3b cannot bind to CR1 on rbc- not transported to phagocytes in liver/spleen- immune complexes not removed via phagocytosis

Question 28

Roles of activated complements

Answer 28

• Creation of membrane attack complex (C5-9)= pores in microbial cell membrane
• Opsonisation (C3b)
• Chemoattractant for leucocytes