11.3 Adaptive Immunity Flashcards
“Immunoglobulin” vs “antibody”: terminology
- Immunoglobulin: Refers only to shape of protein
- Antibody: Specific (e.g. Hep B antibodies)
What happens to a B cell as it moves from a Pro-B cell to a pre-IG B cell?
It expresses an immunoglobulin on the surface that has two “surrogate” light chains; not functional, but in the process of becoming functional.
What Ig isotype is expressed on the surface of an immature B cell?
IgM; Single, not pentameric
What two antibody isotypes are expressed on the surface of a mature, naive B cell?
M and D
Which Chromosome codes for the heavy chain of an immunoglobulin?
Chromosome 14
Which chromosome codes for the light chain of an immunoglobulin?
Chromosome 2
Which is the most common Ig isotype found in the body? Which two isotypes are most associated with an immune response?
- IgG is the most common isotype
- IgM and IgG are associated with an immune response
How long do IgG vs IgM antibodies last in the blood? Why is this significant?
- IgG: 20-21 days
- IgM: 10 days
This is significant because, the longer the antibody can last in the blood, the more likely it is to identify its antigen.
Which antibody classes activate the complement system?
IgM, IgG1, and IgG3
Which isotype of antibody is best transferred across the placenta?
IgG
Which parts of antigens do antibodies bind to?
Epitopes
Is AbAg bonding covalent? How does this affect reversibility?
- Non-covalent
- Therefore, reversible
How many complementary determining region (CDRs) are there on each variable region of an antigen (i.e. each side of the Y)?
Six
In terms of CDRs, what influences the strength of a bond between antibody and antigen?
The more CDRs come into contact with the antigen, the stronger the bond
What are the four possible outcomes of an antibody binding to an antigen?
- Agglutination
- Neutralization (cannot enter tissue)
- Complement activation
- Opsonisation
Explain how the variable portion of an antibody is altered, with reference to the different sections of chromosomes 14 and 2.
- Chromosome 14 (heavy chain) has V, D, and J sections, each of which has multiple segments
- Similarly, Chromosome 2 (light chain) has V and J sections.
- During creation of the variable portion, one of each of these is selected, giving rise to millions of possible antibodies.
Can a B cell ever change the variable portion of its antibody?
Nope
There are 100 antibodies in my bloodstream. 69 of them bind to the antigen. What is the titre value?
69; it’s about the functional amount
Why do we get a small IgG spike during the primary immune response?
Because, during differentiation after clonal expansion, some cells undergo isotype switching to become memory B cells. Upon meeting the antigen, these memory cells proliferate, creating more memory cells as well as IgG plasma cells. This leads to a spike in serum IgG
Describe how somatic hypermutation drives affinity maturation in B cells
- Activated B cells undergo random mutations in the CDR region during proliferation
- This creates a wide range of antibody receptors, some of which are a better fit.
Why are lower affinity antibodies produced during higher antigen dose?
- More antigen -> more chance for lower affinity antibodies to bind to antigen
- Therefore, wider range of antibody shapes produced
What messengers govern which isotype a B cell releases? Which cells release them?
Cytokines released from helper T cells
At a genetic level, how does B cell class switching occur?
- The B cell will use the first isotype gene on the chromosome.
- When a B cell is told to class switch, it sheds all the other genes (leaving a loop of lost DNA), until the correct gene has lined up
What affects whether an antigen is T-dependent or T-independent?
- If an antigen is complicated, it will have many different epitopes
- As a consequence, there is little cross-linking, meaning the signal is not strong enough, and requires T cells
- If the antigen does cross-link, it is T-independent
Are there any memory cells or IgM antibodies produced in a T-independent B cell response?
- No
- No T cell cytokines, no class switching
Based on genetic variability within an individual, how many different variants of MHC class 1/2 can exist in one person?
MHC Class 1: 6
MHC Class 2: 12
Describe antigen processing with MHC Class I
- Endogenous protein broken up into peptides by enzyme
- Funneled into ER
- Loaded on MHC Class 1
- Exported via vesicle onto cell surface
Describe antigen processing with MHC Class II
- Uptake of exogenous antigen
- Lysosomes break it down
- MHC Class II enters endosome from ER
- Peptide loaded onto MHC Class II
- MHC Class II exported to cell surface in vesicle
There is only one type of cell that can activate CD4+ T cells. What is it?
Dendritic cells
What is the role of CD8 and CD4 proteins in MHC:T cell interactions?
- Co-receptor
- Binds alongside antigen/MHC complex to enhance ligand recognition
What causes upregulation of MHC class II and B7 on a dendritic cell?
Recognition of an antigen via a PRR
What 3 signals are required to activate a T cell?
- MHC:peptide synapses with CD4/8 and TCR
- Costimulation: B7 synapses with CD28
- Microenvironment cytokine production
True or false: many kinds of T Helper cells are produced by different cytokines released from the dendritic cell during activation. This is done in equal proportion,
- False
- Many kinds are produced, but not necessarily in equal proportion; varies based on specific immune response
Which molecule on a B cell triggers isotype switching and memory cells?
CD40; this is why T-independent has no memory cells
How do helper T cells help the production of cytotoxic T cells?
They release cytokines that allow differentiation of CD8 -> cytotoxic T cell
