Lecture 10. The Humoral Arm of the Innate Immune Response

Question 1

How long do adaptive immune responses take?

Answer 1

7-10 days

Question 2

What are the three lines of innate immune system defence?

Answer 2

Physical and chemical barriers
Cell-intrinsic response
Specialised proteins and specialised cells

Question 3

What are examples of chemical and physical barriers?

Answer 3

Thick layer of keratinised dead cells – skin Tight junctions between epithelial cells Acidic stomach pH Mucus layers

Question 4

What are examples of cell-intrinsic responses?

Answer 4

Pathogen-induced phagocytosis
Degradation of dsRNA

Question 5

What are examples of specialised protein and specialised cells involved in the innate immune response?

Answer 5

Professional phagocytes – neutrophils, macrophages
NK (natural killer) cells
The complement system

Question 6

Is the innate immune response specific or non-specific to particular pathogens?

Answer 6

Non-specific

Question 7

What are mucus layers?

Answer 7

Skin and other epithelial surfaces lining respiratory, intestinal and urinary tracts provide a physical barrier

Question 8

What is the mucus in the mucus layer made up of?

Answer 8

Secreted mucins and other glycoproteins
It is slippery so hard for pathogens to attach to mucus-coated epithelia

Question 9

What are defensins?

Answer 9

Found in the mucus layer
Small (12-50 amino acids in length) positively-charged antimicrobial peptides, which have hydrophobic or amphipathic helical domains (where the positive charges lie on one face of a coil, and hydrophobic residues lie along another).

Question 10

What can defensins kill or inactivate?

Answer 10

Gram-positive and Gram-negative bacteria
Fungi, including yeasts
Parasites, including protozoa and nematodes
Enveloped viruses such as HIV

Question 11

How do defensins work?

Answer 11

Mechanism remains somewhat uncertain
Their hydrophobic domains or amphipathic helices may enter into the core of the lipid membrane of the pathogen and destabilise it, leading to cell lysis Following membrane disruption, the positive charges may interact with (negatively-charged) nucleic acids in the pathogen

Question 12

How do defensins lyse pathogens, but not our own epithelial surfaces?

Answer 12

They are much more active on membranes that do not contain cholesterol (our membranes contain cholesterol)

Question 13

How does the innate immune system recognise pathogens as ‘non-self’?

Answer 13

The innate immune system recognises molecules (pathogen- associated or microbe-associated immunostimulants) that are common to many pathogens, but essentially absent in the host

Question 14

What are PAMPs?

Answer 14

Pathogen-Associate Molecular Patterns

Question 15

What are PAMPs recognised by?

Answer 15

Soluble receptors in the blood and by cellular receptors

Question 16

What is Toll?

Answer 16

A Drosophila trans-membrane protein with a large extracellular domain with repeating motifs (leucine-rich repeats) that are versatile binding motifs for a variety of proteins

Question 17

What occurs when Toll binds to a pathogenic fungi?

Answer 17

The fungi sends a signal to the nucleus that results in expression of antifungal defensins

Question 18

What is the role of Toll-like receptors?

Answer 18

Act as an alarm system
Most TLRs are on the cell membrane of epithelial cells and macrophages, dendritic cells and neutrophils

Question 19

When was the causative agent of gonorrhea Neisseria gonorrhoeae first desrcibed?

Answer 19

1879

Question 20

What are the symptoms of gonorrhea?

Answer 20

~10% of infected males and ~80% of infected females are asymptomatic
Infection of the genitals can result in a purulent foul-smelling discharge, and via inflammation, dysuria (painful urination) and urethritis, pharyngitis and proctitis

Question 21

What is the chance of a female with an infected man getting gonorrhoea?

Answer 21

~50%

Question 22

What is the chance of a male with an infected woman getting gonorrhoea?

Answer 22

~20%

Question 23

What is the average age of people with gonorrhoea?

Answer 23

15-24

Question 24

How does Neisseria Gonorrhoeae function?

Answer 24

The capsule of N. gonorrhoeae lacks lipopolysaccharide (LPS): instead, it contains lipooligosaccharide (LOS)
N. gonorrhoeae can utilise host-derived sialic acid to sialylate its LOS