12 - Biological Roles of Immunoglobulins - Partridge Flashcards

1
Q

List the 6 biological roles of Immunoglobulins including the Abs that allow each of these functions to occur (sometimes an example isn’t give)

A
  • label pathogen for elimination/destruction
  • reduce its movement. eg IgM binds to flagella to immobilise bacteria
  • form immune complexes when multiple Abs bind to soluble antigen eg IgM/IgG
  • agglutinate particles (bacteria) so they’re easily cleared by defence molecules
  • neutralise toxins (IgA, IgG)
  • prevent interaction of pathogen with host cells (IgA, IgG)
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2
Q

Describe the difference between avidity and affinity and give an example of a molecule with high avidity but low affinity

A

AVIDITY;
relates the size and the no. binding sites of the Ab to its ability to bind to pathogen
AFFINITY;
strength of the interaction between the Fab arm and the antigen
eg IgM

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3
Q

When talking about multivalency, Abs are at least ____

A

divalent

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4
Q

What are the 3 Fc effector functions?

A
  • invoke the destruction of the pathogen
  • activate complement (IgG/IgM)
  • bind Fc receptors on leucocyte surfaces (IgG/A/E)
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5
Q

What do the 3 Fc effector functions depend on? (2)

A
  • stages of the immune response (1ry/2ndry)

- site of infection and the types of pathogen involved

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6
Q

What are the 3 pathways of complement activation and what is the central event in all of these?

A

classical, alternative, MB lectin

cleavage of C3 component -> C3a + C3b

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7
Q

Describe the classical pathway in terms of the no. Abs needed to activate it, the components involved and draw a diagram

A
  • involves C1 molceule = C1q + C1r + C1s
  • requires C1q making at least 2 interactions to Fc regions (eg 2 IgGs or pentameric IgM)
  • binding to Fc -> activates C1r which then cleaves and activates C1s -> cleaves C2 and C4 -> C4bC2a (C3 converts)
  • C1r + s = Ser proteases. exist as complex with C1qr2s2 with Ca2+ holding complex together
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8
Q

List the order in which the Abs (and their subclasses) can activate the classical pathway with the most potent being first

A

IgM > IgG3 > IgG1 > IgG2

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9
Q

What are the results of complement activation?

A
  • lysis of cells
  • activation of leucocytes
  • inducer of inflammation (allowing immune cells to reach the location where theyre needed)
  • opsonisation of pathogen
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10
Q

give examples of the effector cells that express FcRs

A
  • NK cells
  • mononuclear phagocytes
  • granulocytes eg basophils, mast cells
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11
Q

Describe the complex of an FcR

A

Overall; multisubunit complex
different iso forms depending on the Ig they bind (IgG/A/E) eg FceR has many intracellular domains invovled in signalling
- alpha chains bind Fc regions
- associated chains have functions in downstream signalling and cell surface expression
- ITIM/ITAM intracellular motifs (immunoreceptor tyr inhibitory/activation motifs). have roles in activating/suppressing immune response once pathogen has been dealt with

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12
Q

Why is the activation of an FcR dependent upon it binding to Ab bound to antigen?

A

Ab is cross linked when bound to antigen

FcR is cross linked when binding to Ab

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13
Q

What are the 2 Ig classes that can bind to FcRs on phagocytes and list the affinity of the subclasses to these FcRs

A

IgG, IgA

IgG1=3>4

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14
Q

What are the 5 results when the FcRs on phagocytes are bound by Abs?

A
  • cell activation (inducing phagocytosis etc)
  • opsonisation of the Ab-bound pathogen
  • respiratory burst and release of O2 intermediates in the phagosome
  • clearance of immune complexes
  • frustrated phagocytosis - release of lysosomal contents in the pathogen is too big to be phagocytosed
    IF FcRs are present on APC eg DCs, then the bacterial peptides produced can be presented on the surface associated w/ MHC molecules
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15
Q

Draw a diagram illustrating how phagocytosis occurs of an opsonised pathogen

A

dont forget about the cross linking of the FcRs

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16
Q

Draw a diagram showing how FcRs can cross link when they bind Ab.

A

word

17
Q

What is the Ig class that binds to FcRs on NK cells? What is the name of the R on Nk CELLS?

A

IgG (IgG1=3)

Fc(gamma)RIII

18
Q

What happens when the FcR of NK cells is bound by its Ab?

A
  • FcR on NK recognise Ab bound to target cell
  • cross linking of Fc receptors causes cell activation and release of granule contents eg enzymes and perforin
  • the target cell is killed by apoptosis
    in other words ANTIBODY DEPENDENT CELL-MEDIATED CYTOTOXICITY
19
Q

What type of infections are NK cells effective against?

A

viral infections. virally infected cells often express viral proteins on their surfaces which are bound by Ab

20
Q

What is TRIM21?

A

intracellular cytosolic receptor for IgG

21
Q

What does TRIM21 do/is involved in?

A

intracellular hummoral immunity
recognises internalised IgG that is bound to viruses (v high affinity for IgG) and targets the virus to the proteasome by adding on ubiquitin to the protein (this also leads to viral protein surface expression to CTT)

22
Q

What type of Ab do the FcRs on mast cells/basophils recognise? What are the functions of mast cells?

A

IgE
effetive against parasitic infections. allergy responses
release inflammatory mediators and cytokines

23
Q

What are NUDE mice?

A

have no thymus therefore no T cell responses

24
Q

Give an example of a thymus independent antigen and the responses it induces

A

bacterial polysaccharide

  • B cells can rapidly produce high levels of IgM Abs
  • memory response not created
25
Q

Give an example of a thymus dependent antigen and the responses it induces

A
proteins 
- T cells allow B cells to differentiate into plasma cells during the response 
- long - lived memory B cells generated 
- T cell help allows somatic hypermutation and class switching 
(T cell subsets and cytokines they produced influence the class/subclass of Ab that are produced by B cells in humeral response)