12 - Biological Roles of Immunoglobulins - Partridge

Question 1

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

Answer 1

• 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)

Question 2

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

Answer 2

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

Question 3

When talking about multivalency, Abs are at least ____

Answer 3

divalent

Question 4

What are the 3 Fc effector functions?

Answer 4

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

Question 5

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

Answer 5

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

- site of infection and the types of pathogen involved

Question 6

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

Answer 6

classical, alternative, MB lectin

cleavage of C3 component -> C3a + C3b

Question 7

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

Answer 7

• 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

Question 8

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

Answer 8

IgM > IgG3 > IgG1 > IgG2

Question 9

What are the results of complement activation?

Answer 9

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

Question 10

give examples of the effector cells that express FcRs

Answer 10

• NK cells
• mononuclear phagocytes
• granulocytes eg basophils, mast cells

Question 11

Describe the complex of an FcR

Answer 11

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

Question 12

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

Answer 12

Ab is cross linked when bound to antigen

FcR is cross linked when binding to Ab

Question 13

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

Answer 13

IgG, IgA

IgG1=3>4

Question 14

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

Answer 14

• 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

Question 15

Draw a diagram illustrating how phagocytosis occurs of an opsonised pathogen

Answer 15

dont forget about the cross linking of the FcRs

Question 16

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

Answer 16

word

Question 17

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

Answer 17

IgG (IgG1=3)

Fc(gamma)RIII

Question 18

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

Answer 18

• 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

Question 19

What type of infections are NK cells effective against?

Answer 19

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

Question 20

What is TRIM21?

Answer 20

intracellular cytosolic receptor for IgG

Question 21

What does TRIM21 do/is involved in?

Answer 21

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)

Question 22

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

Answer 22

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

Question 23

What are NUDE mice?

Answer 23

have no thymus therefore no T cell responses

Question 24

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

Answer 24

bacterial polysaccharide

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

Question 25

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

Answer 25

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)