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IIH > Innate immune system > Flashcards

Innate immune system Flashcards

1
Q

What is an innate immune response?

A

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

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2
Q

Which cells form the innate immune system?

A 
DC
Phagocytes
Macrophages
Mast cells
NK cells
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3
Q

What is the function of a DC?

A

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.

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4
Q

Where are DC most abundant?

A

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

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5
Q

What is a phagocyte?

A

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

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6
Q

What type of immune cells are phagocytes?

A

Macrophages - target slow replicating bacteria

Granulocytes - Neutrophils, basophils, eosinophils

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7
Q

Which phagocytes do not have lysosomal enzymes?

A

Basophils and mast cells

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8
Q

What is a macrophage?

A

A matured monocyte that engulfs dying neutrophils and tissue cells.

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9
Q

Where are macrophages found in clusters?

A

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.

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10
Q

What is the function of mast cells?

A

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

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11
Q

What mediators are released from mast cells?

A

Histamine, Tryptase, heparin, Kallikrein —> bradykinin

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12
Q

What is a NK cell?

A

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

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13
Q

Why are symptoms produced?

A

The response to an antigen causes damage to self.

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14
Q

How are non self pathogens recognised in the innate system?

A

Pattern recognition receptors and complement

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15
Q

What is a PRR?

A

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

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16
Q

What is a PAMP?

A

Pathogen associated molecular pattern

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17
Q

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

A

TLRs - TOLL like rececptors

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18
Q

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

A

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.

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19
Q

What is the complement cascade?

A

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

20
Q

What is the cascade based around?

A

Coversion of C3 to C3b.

21
Q

What is the function of C3b?

A

An insoluble protein that binds to a pathogen to:

  • Opsonise for phagocytosis
  • Formation of MAC to create pores
22
Q

How is C3b prevented from binding to self cells?

A

C3b is converted to iC3b using Factor H/I

23
Q

Which pathways allow the conversion of C3 to C3b?

A

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

24
Q

How is the Alternative pathway activated?

A

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

25
Q

What does an activated alternative pathway result in?

A

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

26
Q

How does the MBL pathway function?

A

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.

27
Q

Where is MBL produced and how?

A

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.

28
Q

Where does CRP bind?

A

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

29
Q

What is the classical pathway?

A

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.

30
Q

What do all three of the pathways result in?

A

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

31
Q

What does the conversion of C3 to C3b do?

A

Makes the soluble C3 an insoluble C3b.

32
Q

What function other than opsonisation does C3b have?

A

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

33
Q

What is the terminal lytic pathway?

A

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

34
Q

What does MAC do?

A

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.

35
Q

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

A

C3b is recognised by CR1

iC3b is recognised by CR3/4 to prevent self attack

36
Q

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

A

C3a = induces degranulation of MAST cells.

37
Q

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

A

C5a = Attracts NEUTROPHILS to the site

38
Q

What does a high level of C3 and C4 suggest?

A

Infection

39
Q

Which pathway is C4 specific to?

A

MBL and CLASSICAL

40
Q

What can be used to investigate angioedema?

A

C1 inhibitor

41
Q

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

A

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

42
Q

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

A

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)

43
Q

What is C1 esterase inhibitor?

A

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

44
Q

What is C1 esterase inhibitor deficiency?

A

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.

45
Q

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

A

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.

46
Q

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

A

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

IIH (19 decks)

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