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Immunohematology and Serology > Chapter 5 - Complement > Flashcards

Chapter 5 - Complement Flashcards

1
Q
  • What type of cells can be lysed by complement?

- What happens to the other cells?

A
  • relatively fragile cell types
    Gram negative bacteria and RBCs
  • they are opsonized
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2
Q

Complement

  • how many different proteins are there?
  • what organs/cells produce it?
A
  • About 35 different proteins

- Synthesized by the liver, monocytes, macrophages and epithelial cells

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3
Q

Complement

  • when can synthesis increase
  • when can the levels decrease?
A
  • increases in acute inflammation so the levels of complement components can rise
  • In chronic inflammation or in liver disease the levels can decrease
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4
Q

How does complement help the host fight infection chemically?

A
  • Lysis, opsonization, chemotaxis, leukocyte activation
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5
Q
  • What type of cells does complement clear from the body?

- What pathway does it interact with?

A
  • Clearance of immune complexes
  • Clearance of apoptotic cells
  • Interacts with the coagulation pathway
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6
Q

Functions of Complement

- what role does it play in innate and acquired immunity?

A

Helps join the forces of the innate immune system with the acquired immune system

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7
Q

Functions of Complement

- what role does C3b and C4b have on the innate/acquired immune system?

A
  • C3b, C4b, and other fragments have roles in the activation of B cells and antigen presenting cells
  • Enhances memory through interactions with B cells and follicular dendritic cells
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8
Q

Complement activation pathways

  • what are the three pathways?
  • what do the pathways all lead to?
  • what complement fragment do all of these pathways activate?
A

Pathways

  • Classical pathway
  • Alternative pathway
  • Lectin pathway
  • All lead to cell lysis
  • Three different ways to activate C3
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9
Q

Complement activation pathways

- what happens after C3 is activated?

A
  • After the activation of C3 all pathways converge and activate components C5–9 in succession
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10
Q

Complement components

  • how are they identified?
  • how are they activated?
  • how are they written once activated?
A
  • Numbered
  • Activated by one or more of the activated components before it
  • Activated complex is denoted by a bar over the top
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11
Q

Functions of Complement: cleavage

  • what happens to the cleaved product pieces?
  • how is each piece named?
A
  • Larger cleavage product lands on the cell that initiated the activation, smaller piece floats away
  • When the component is broken into two pieces the pieces are called a and b (i.e., C3a and C3b)
  • Further breakdown forms other pieces like C3d
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12
Q

Complement conventions

  • which piece of the cleaved complement tends to “float away”?
  • where does it go?
  • what is the exception to this convention?
A
  • The piece that floats away and has its biological activities in solution is the “a” component
  • Exception is C2; C2a lands on the surface of the cell and C2b floats away
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13
Q

What is a convertase and how is it labeled?

A
  • A component that has enzyme activity and effects the next piece is called a convertase, as in C4bC2a is called C3 convertase
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14
Q

Classical pathway

- how is it initiated?

A
  • Initiated by antibody bound to antigen

- - Activated by IgM and the IgG subclasses, IgG3, IgG1 and IgG2 (in order of their efficiency)

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15
Q

Classical pathway

- what happens after the antibody binds to the antigen?

A
  • After antibody binds to antigen, a conformational change occurs
    • Reveals a site on the antibody molecule that binds the C1q molecule
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16
Q

Classical pathway

- aside from Ab-Ag bonding, how can C1q be activated?

A
  • C-reactive protein
  • some gram negative bacteria including E. coli
  • several viruses
  • some protozoa
  • some mycoplasmas
  • factor XXIIa of the coagulation pathway
17
Q

Formation of C3 Convertase: Classical pathway

- how does it happen?

A
  • Combination of the acquired (antibodies) and the innate (complement proteins) immune systems to destroy bacteria
18
Q

Formation of C3 Convertase: Alternative pathway

  • how does it happen?
    • what are some examples?
A
  • Microorganisms and certain structures called activator surfaces can directly interact and initiate the complement cascade
    • LPS in bacterial cell walls, fungi, viruses
    • Some parasites including trypanosomes, endotoxins
    • Aggregated IgG2, IgA, IgE are all activator surfaces
19
Q

Formation of C3 Convertase: Lectin pathway

- how does it happen?

A
  • Either MBL or serum ficolin bind to surface terminal carbohydrates that have either mannose or N-acetylgalactosamine as a nonreducing terminus on the pathogen
  • MASP-2 binds to the MBL and cleaves C2 and C4, creating C2a and C2b and C4a and C4b
  • C2b and C4a diffuse away and C2aC4b forms C3 convertase
20
Q

Complement system

  • what type of pathogens does it clear?
  • increase or decrease inflammation?
A
  • Clears
    • Bacteria
    • Viruses
    • Immune complexes
  • Increases inflammation
21
Q

Complement system

  • what happens if left unchecked?
  • where are the controls located?
A
  • Left unchecked can cause severe cell and tissue damage

- Controls in the fluid phase and on the cell surfaces

22
Q
  • What is DAF?
  • Where is it found?
  • What does it do?
A
  • Decay-accelerating factor/CD55
  • On most cells
  • Keeps cells from being hurt by bystander lysis
23
Q

Measurement of Components

- what are the two types of assays and what do they measure?

A
  • Antigenic assays
    • Measure the amount of each protein using traditional serologic assays
  • Functional assays
    • Lytic function of the components is measured
24
Q

Functional Assays

- what are the two types and what do they measure?

A

CH50 assay

  • Measures the function of complement initiated through the classical pathway
    • Srbc lysis and hemoglobin measurement
    • Newer test measures neoantigen formation with formation of Membrane Attack Complex

AH50 assay
- Measures the function of complement initiated through the alternative pathway

25
Q

AH50 assay

  • how is it performed?
  • how is it measured?
A
  • Rabbit red blood cells are mixed with the serum

- Amount of hemoglobin released by the cells is proportional to amount of alternative pathway activity

26
Q

What components are required by the CH50 assay?

A
  • C3
  • C5 through C9
  • C1
  • C2
  • C4
  • C1 INH
27
Q

What components are required by the AH50 assay?

A
  • C3
  • C5 through C9
  • Factor B
  • Factor D
  • Properdin
  • Factor H
  • Factor I
28
Q

Antigen Assays: Serologic tests

- how can individual components be measured?

A
  • by radial immunodiffusion
29
Q

Antigen Assays: Serologic tests

  • what does an increased C4a mean?
  • what does an increased Bb mean?
  • how is terminal pathway activation measured?
A
  • Increases in C4a indicates complement activation (classical or lectin pathway)
  • Increases in Bb indicates complement activation (alternative pathway)
  • Terminal pathway activation can be measured by measuring C3a, C5a and SC5b-9
30
Q

Antigen Assays

  • what can cause high complement levels?
  • what can cause low complement levels?
A

High Complement levels
- Acute inflammation can raise C levels

Low Complement levels

  • Genetic deficiencies
  • Chronic infection
  • Incorrectly processed serum samples
    • obtain in a red top
    • separate, freeze, and store at -70°C
31
Q

Complement Deficiencies

- what do deficiencies in C1, C4, and C2 recognition increases risk of ?

A
  • Autoimmune connective tissue diseases such as SLE

- Recurrent infections with Staphylococcus and Streptococcus

32
Q

Complement Deficiencies

- what are deficiencies in the lectin pathway associated with?

A
  • Associated with bacterial infections in infants
33
Q

Complement Deficiencies

- what are deficiencies in the C1 INH pathway associated with?

A
  • Involved in inhibiting both the classical and lectin pathways
  • Can cause hereditary angioedema, rapid swelling of the effected site
34
Q

Complement Deficiencies

- what do deficiencies in C3 effect?

A
  • Profound affect all pathways
  • Decrease Phagocytosis
  • Decrease Immune complex clearance
  • Decrease class switching from IgM to IgG
35
Q

Complement Deficiencies

- what do deficiencies in the alternative pathway effect?

A
  • Related to pus forming infections
36
Q

Complement Deficiencies

- what happens when there are deficiencies in terminal components (MAC)?

A
  • Severe Neisseria meningitides infections

- SLE

37
Q

Complement Deficiencies

- what do deficiencies in DAF and CD59 effect?

A
  • Paroxysmal nocturnal hemoglobinuria

- Anemia

Immunohematology and Serology (8 decks)

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