Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MIIM30002 - Principles of Immunology > Lecture 26 - Complement Activation 2 > Flashcards

Lecture 26 - Complement Activation 2 Flashcards

1
Q

Describe the mechanism of Opsonisation and Phagocytosis in the C’ cascade

A
  1. C3b and C4b binds to the surface of microbes
  2. Macrophages bind C3b through CR1
  3. Macrophages bind Ab on microbe surface through FcγR
  4. Receptor mediated endocytosis
  5. Destruction of microbe in phagosome with hydrolytic enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How are the recognition molecules (responsible for initiation of C’ cascade) like pattern recognition receptors?

A

They recognise PAMPs on the surfaces of pathogens:

MBL: sugars (mannose)
CRP: phosphocholine
C3b: amino acids and hydroxyl groups

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is an opsonin?

A

Material that coats pathogens to promote opsonisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the various complement receptors?

Which cells are they expressed on?

A 
CR1
 • aka CD35
 • Macrophages, neutrophils, RBCs, FDCs
 • Bind C3b, C4b, iC3b
 • Important role in C3 convertase regulation

CR3
• aka Mac-1
• Macrophages

CR2:
• B cells, FDCs

CR4:
• DCs
• similar function to CR3

Expression on:
Phagocytes:
• macrophages
• neutrophils

CR1 also on:
• FDCs
• RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is iC3b?

Which CRs will bind it?

A

A breakdown product of C3b
Forms on cell membranes
Binds C’ receptors, especially CR3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How do macrophages recognise opsonised microbes most efficiently?

A

Recognition through:

  • CR1 : C3b
  • FcγR : IgG
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe RBC use of C’ receptors

A

RBC express CR1

  1. CR1 binds Ab-Ag complexes in blood
  2. RBCs circulate (with immune complexes bound) to the spleen
  3. Complexes stripped from the RBC in the spleen
  4. RBCs survive and recirculate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the function of CR2?

A

Forms complex with CD19 and CD81 (also present in membrane of B cell)

Provides ‘second’ signal for B cell activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the role of C’ in B cell activation

A

The following are expressed on the surface of B cells:
• BCR (e.g. IgM)
• CR2
• CD19, CD81

  1. Microbe bound by C3dg
  2. Ag on microbes bind CDRs on BCR
  3. C3dg on microbe binds CR2
  4. Triggering of transduction pathway, leading to B cell activation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which C’ receptors do FDCs express?

A

CR1

CR2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which C’ receptors do DCs express?

A

CR4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the interaction between EBV and B cells

A

CR2 present on B cells

EBV uses this receptor to get into B cells

Remains latent in B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is C3dg?

What is its receptor?

A

C3dg is another breakdown product of C3b

C3dg is a ligand for CR2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is an anaphylatoxin?

Give some examples

A

Molecules that can cause systemic inflammation, and possibly lead to anaphylactic shock

Leads to a massive drop in BP (through systemic vasodilation)

Examples:
• C3a
• C5a

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe triggering of inflammation through the C’ cascade

A

Mediated by C3a and C5a

  1. Cleavage of C3 and C5 through the C’ cascade to deliver:
    • C3a
    • C5a
  2. C3a and C5a bind to their receptors expressed on:
    • Mast cells
    • Endothelial cells
    • Phagocytes
  3. Release of TNF and histamine from these cells
  4. TNF and Histamine, as C3a, C4a and C5a:
    → Increase in vascular permeability
  5. Migration of leukocytes into tissues → tissue inflammation
  6. C5a acts as a chemoattractant for Neutoprhils and monocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Where are the receptors for C5a and C3a located?

A

Mast cells
Endothelial cells
Phagocytes

17
Q

Describe chemoattraction through the C’ cascade

A

Mediated by C5a

  1. C5a generated through cleavage of C5 in the C’ cascade
  2. C5a binds to C5aR (GPCR) expressed on:
    • Neutrophils
    • Monocytes
  3. Triggering of transduction cascade in the cells

→ Motility towards the source of C5a

18
Q

What is the structure of C3aR and C5aR?

A

GPCRs

19
Q

Which sort of pathogens are targeted by the C’ cascade?

A

Bacteria
Free virions
Parasites

20
Q

Which factors regulate C3 convertase production?

A

DAF
CR1
MCP

21
Q

Which molecule cleaves and inactivates C3b?

A

Factor I

and Factor H assisting

22
Q

Which molecule inhibits MAC formation?

A

CD59

23
Q

What are some of the host regulatory proteins that prevent C’ damage of our own cells?

A 
CD59
DAF
CR1
MCP
Factor I
Factor H
24
Q 
Describe the function of:
 • MCP
 • CD59
 • Factor H
 • DAF
 • CR1
 • Factor I
A

Host cell regulatory proteins

CD59:
• Inhibition of MAC formation

DAF:
• Regulation of C3 convertase production
• Classical and Alternative pathways

CR1
• Regulation of C3 convertase production
• Classical and Alternative pathways

MCP
• Regulation of C3 convertase production
• Classical pathway only

Factor I:
• Degradation of C3b

Factor H
• Degradation of C3b

25
Q

Describe inhibition of C3 convertase

A

Mediated by:
• DAF
• CR1
• MCP

– Classical pathway –

  1. Formation of C4bC2a on Ig bound to Ag on host cells
  2. DAF/CR1/MCP expressed in the cell membrane of host cells
  3. DAF/CR1/MCP displaces C2a from C4b

– Alternative pathway –

  1. C3bBb forms on host cell surface
  2. DAF/CR1 (expressed on host cells) displaces Bb from C3b
26
Q

Describe the function of Factor I

What type of molecule is it?

A

It is a serine protease

  1. C3b present in the fluid phase, bound covalently to cells
  2. Factor I binds to C3b
    MCP/CR1 (present in host cell membrane) associate with C3b
  3. Proteolysis of C3b
    C3b → iC3b / C3d / C3dg
  4. Degradation products bind to CR on phagocytes and B cells (clearance)
27
Q

Describe regulation of MAC formation

A

Mediated by CD59

  1. Activation of C5bC6C7C8 in late stages of C’ cascade
  2. CD59 (expressed on host cells) interferes with polymerisation of C9 pore

→ no MAC formed in host cells

28
Q

Which co-factors are required for Factor I function?

A

Factor H
MCP
CR1

29
Q

Which cells does Factor H bind?

A

Cell surfaces rich in sialic acid (mammalian cells)

→ helps clear C3b on host cells

30
Q

Describe the role of C’ components in the following processes:
• Solubilisation of immune complexes
• Clearance of immune complexes

A

Immune complexes form all the time

Solubilisation:
C’ deposited on immune complexes makes them more soluble

Clearance:
Immune complexes with C’ attached will bind to CR1 on RBCs
When these circulate to the spleen, they are stripped off and phagocytosed
The RBCs survive and recirculate

31
Q

How can microbes evade the complement system?

A

Expression of homologues of the host complement regulatory proteins:

  1. Expression of sialic acid
  2. Expression of proteins that recruit Factor H
    • e.g. HIV gp41 recruits Factor H
  3. Virus budding incorporating the host regulatory proteins DAF and CD59
  4. Production of specific proteins that mimic C’ proteins
    • E. coli produce C1q
  5. Inhibition of C’ mediated inflammation
    • S. aureus produce CHIPS
32
Q

What is the basis of ABO blood groups?

A

Glycans (complex sugars) present on the cell surface

A allele: terminal N-acetylgalactosamine

B allele: terminal galactose

O allele: enzyme not present, so no terminal sugars

33
Q

Why is there rejection of blood in transfusion?
Outline the process

What are the symptoms of mis-matched blood transfusion?

A

“Natural IgM” antibodies are present against sugars in the other blood group

NB Rh blood groups can also activate C’

e.g. A individual:
• IgM against terminal galactose residues

  1. Blood transfusion from B individual to A individual
  2. anti-B Ab from host bind to terminal galactose sugar on donor RBCs
  3. Activation of C’
4. Lysis of RBCs
Fever
Nausea
Vomiting
Pain
Shock
34
Q 
From whom can the following individuals receive blood:
 • A
 • B
 • AB
 • O?

Which Ab do they respectively have?

A

A:
• A
• O
• Have anti-B Ab

B:
• B
• O
• Have anti-A Ab

AB:
 • A
 • B
 • O
 • Have no Ab

O:
• O
• Have anti-A and anti-B Ab

35
Q

What are some C’ deficiency diseases?

What does it leave the people susceptible to?

A

Classical pathway:
• C1, C2, C4 deficiency
→ SLE

Alternative pathway:
• Factors B, D and properdin deficiency
→ Increase infection susceptibility: Neisseria

Alternative and classical pathway:
• C3 deficiency
→ Increased infection susceptibility to S. pneumoniae, Neisseria, H. influenzae

36
Q

What are the receptors for the following:
• C3a
• C5a

A

C3a: C3aR
C5a: C5aR

37
Q

Describe the products of Factor I proteolysis of C3b

A

C3B → iC3b + C3dg

Also: C3d (binds to CR-2)

38
Q 
Which C' components do the following receptors bind:
 • CR1
 • CR2
 • CR3
 • CR4
A

CR1:
• C3b
• C4b

CR2:
 • C3d
 • C3dg
 • iC3b
i.e. the breakdown products of C3b

CR3:
• iC3b

CR4:
• iC3b

MIIM30002 - Principles of Immunology (30 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions