Innate immune system

Question 1

What is an innate immune response?

Answer 1

A non-specific response to an pathogen on the first encounter of its antigen.

Question 2

Which cells form the innate immune system?

Answer 2

DC
Phagocytes
Macrophages
Mast cells
NK cells

Question 3

What is the function of a DC?

Answer 3

Found in all tissues, acting as the interface between innate and adaptive by acting as APC through MHC mollecules.
Can migrate to T cell rich areas in lymphoid tissue to transmit signals through TOLL receptors to instruct the type of T cell response needed.

Question 4

Where are DC most abundant?

Answer 4

At the surface of stratified squamous tissues as Langerhan’s.

Question 5

What is a phagocyte?

Answer 5

A cell which engulfs a pathogen to kill it via the release of enzymes and toxic substances from its granules and lysosomes.

Question 6

What type of immune cells are phagocytes?

Answer 6

Macrophages - target slow replicating bacteria

Granulocytes - Neutrophils, basophils, eosinophils

Question 7

Which phagocytes do not have lysosomal enzymes?

Answer 7

Basophils and mast cells

Question 8

What is a macrophage?

Answer 8

A matured monocyte that engulfs dying neutrophils and tissue cells.

Question 9

Where are macrophages found in clusters?

Answer 9

Line the sinusoids of liver as Kupffer cells for the drainage of intestines and spleen.
Also found in the red pulp of spleen, perfused by sinusoids of splenic A to destroy any blood cells.

Question 10

What is the function of mast cells?

Answer 10

Degranulate on activation to release inflammatory mediators in response to tissue damage.

Question 11

What mediators are released from mast cells?

Answer 11

Histamine, Tryptase, heparin, Kallikrein —> bradykinin

Question 12

What is a NK cell?

Answer 12

Induces death of infected cell that is not expressing MHC molecules when infected by virus or tumour.

Question 13

Why are symptoms produced?

Answer 13

The response to an antigen causes damage to self.

Question 14

How are non self pathogens recognised in the innate system?

Answer 14

Pattern recognition receptors and complement

Question 15

What is a PRR?

Answer 15

Receptors on innate immune cells that recognise nonself cells through PAMPs.

Question 16

What is a PAMP?

Answer 16

Pathogen associated molecular pattern

Question 17

What type of receptor is the most common type of PRR for signalling?

Answer 17

TLRs - TOLL like rececptors

Question 18

How do TLRs signal? What response does this result in?

Answer 18

Can be expressed both intra and extracellularly. Signal through MyD88 and NFkappaB. The detect PAMPs upon enzymatic degradation with phagolysomes to trigger a cascade that activates genes within the cell to upregulate inflammatory cytokines IL and TNFalpha.

Question 19

What is the complement cascade?

Answer 19

A system of soluble proenzymes found in the blood and tissue fluids that are activated via a cascade to remove pathogens.

Question 20

What is the cascade based around?

Answer 20

Coversion of C3 to C3b.

Question 21

What is the function of C3b?

Answer 21

An insoluble protein that binds to a pathogen to:

• Opsonise for phagocytosis
• Formation of MAC to create pores

Question 22

How is C3b prevented from binding to self cells?

Answer 22

C3b is converted to iC3b using Factor H/I

Question 23

Which pathways allow the conversion of C3 to C3b?

Answer 23

Occurs spontaneously in the ALTERNATIVE pathway or through the production of C3 convertase in the MBL and CLASSICAL pathway.

Question 24

How is the Alternative pathway activated?

Answer 24

Activated by endotoxins and bacterial cell walls during non-specific response.

Question 25

What does an activated alternative pathway result in?

Answer 25

It relies on soluble C3 from blood and tissue fluids to spontaneously convert to C3b. In the presence of factor B and D, C3b will produce C3 convertase for +ve feedback or produce C5 convertase

Question 26

How does the MBL pathway function?

Answer 26

Mannose binding lectin is a PRR that binds to mannose in the cell wall of pathogens to trigger the cascade. It results in the production of C3 convertase from C4 and C2.

Question 27

Where is MBL produced and how?

Answer 27

When macrophages are activated they release cytokines to alert the immune system. IL-1beta and IL-6 act on the liver to produce MBL and CRP.

Question 28

Where does CRP bind?

Answer 28

To phosporylcholine. Can bind to form a complex that will activate the classical pathway

Question 29

What is the classical pathway?

Answer 29

This is the pathway for an ADAPTIVE response. The formation of an antigen-antibody complex allows C1q to bind to IgM or IgG in the complex to result in the production of C3 convertase through C4 and C2.

Question 30

What do all three of the pathways result in?

Answer 30

Production of C3 CONVERTASE for the conversion of C3 to C3b for OPSONISATION.

Question 31

What does the conversion of C3 to C3b do?

Answer 31

Makes the soluble C3 an insoluble C3b.

Question 32

What function other than opsonisation does C3b have?

Answer 32

C3b continues down the cascade to activate C5 convertase for the TERMINAL LYTIC PATHWAY.

Question 33

What is the terminal lytic pathway?

Answer 33

C5 convertase converts C5 to C5b which can then associated with components C6-9 to from a ringed complex called MAC.

Question 34

What does MAC do?

Answer 34

MAC binds to cell membranes to create a pore. If enough pores are created, the volume of water entering the cell will cause swelling and lysis.

Question 35

How do neutrophils and macrophages identify C3b for phagocytosis and killing?

Answer 35

C3b is recognised by CR1 | iC3b is recognised by CR3/4 to prevent self attack

Question 36

What is the byproduct produced by C3 convertase and what is its function?

Answer 36

C3a = induces degranulation of MAST cells.

Question 37

What is the byproduct of C5 convertase and what is its function?

Answer 37

C5a = Attracts NEUTROPHILS to the site

Question 38

What does a high level of C3 and C4 suggest?

Answer 38

Infection

Question 39

Which pathway is C4 specific to?

Answer 39

MBL and CLASSICAL

Question 40

What can be used to investigate angioedema?

Answer 40

C1 inhibitor

Question 41

What may cause a low C4 and what does it show?

Answer 41

Defect in CLASSICAL PATHWAY: Hereditary mutation that inactivates upto half of its 4 alleles causing a partial deficiency or due to immune complex disease such as lupus. Acquired due to consumption or overactivation of the classical pathway e.g. lupus, rheumatoid vasculitis, cryoglobinaemia

Question 42

How does a Pt with a total deficiency of C4 present?

Answer 42

Rare but would have recurrent infections from ENCAPSULATED bacteria as the CLASSICAL pathway is not working (Requires antibodies to be able to recognise the antigens that are concealed by the capsule)

Question 43

What is C1 esterase inhibitor?

Answer 43

A control protein that blocks the CLASSICAL pathway and BRADYKININ pathway.

Question 44

What is C1 esterase inhibitor deficiency?

Answer 44

Causes hereditary angioedema due to increased vascular permeability from an unopposed bradykinin response and has LOW C4 as it is used up by the continuous activation of the classical pathway.

Question 45

What can cause a low C3 and what does it suggest?

Answer 45

Can show a defect in alterantive or classical. A mutation in any protein in the ALTERNATIVE pathway caused by a rare inherited disease e.g. C3, factor H or factor I deficiences. Acquired deficiency in C3 on exposure to post-streptococcal glomerulonephritis.

Question 46

How does a Pt with a defect in the classical pathway present?

Answer 46

Have increased susceptibility to Neissera meningitides meningitis and will present with more than one episode of bacterial meningitis.