Exam 3: Humoral Immune II Flashcards
what do naïve B cells express that function as antigen receptors
IgM
IgG
what happens every time there is an immune response from the same antigen
antibodies have a higher affinity for the antigen
Do secreted antibodies have the same specificity as that of the naïve B cell membrane receptors that recognize antigens?
Yes
how many plasma cells to B cells generate once activated?
how many antibodies can they produce a day?
Once activated B cells can generate up to 4000 plasma cells
Can produce up to 10^12 antibody molecules per day
what is heavy chain isotype (class) switching
Some B cells may begin to produce antibodies with different heavy chain isotypes (classes), which mediate different effector functions and are specialized to combat different types of microbes
What is affinity maturation
repeated exposure to an antigen results in the production of antibodies with increased affinity
High affinity antignes
fit properly with antigen-binding site
maximum number of interactions occur
B cell co-receptors
bind to fragments of complement proteins and deliver an additional signal to the B cell nucleus
CD19 and CD21 interaction
when CD21 binds to CD19 –> increased activation of CD19
B cell travel through lymph nodes
Naive B cells leave bone marrow via blood
May encounter antigens in blood, lymph, or lymph nodes
If they don’t bind to an antigen or fail to find the correct Th cell they leave via efferent lymphatic vessels and move on to next lymph node
What are HEVs
specialized venules inside lymph nodes and peyer’s patches that have receptors for cell-surface proteins on T and B cells
This interaction allows T and B cells to exit the blood and enter lymph nodes
Inside Th cells encounter antigen presenting dendritic cells
Antigen processing and presentation by B cells inside Lymph Node
Mammalian B cell BCRs bind to antigen. Then via receptor mediated endocytosis, internalize the antigen-antibody complex.
The newly formed endosomes fuse with the lysosomes that contain both proteolytic enzymes and MHC II molecules.
The antigenic peptides bind to the MHC molecules and the MHC-antigen complexes return to the surface for presentation to Th cells.
B cells proliferate in lymph nodes germinal centers
After activation in the medulla, a large population of B cells moves to lymphoid follicles, proliferate, and form germinal centers
what are dividing B cells called
what are resting B cells called
dividing B cells - centroblast
Resting B cells - centrocytes
what types of cells do germinal centers contain
Centroblasts
Centrocytes
Th cells
Follicular dendritic cells
what happens to B cells in germinal centers
B cells undergo isotype switching and somatic hypermutation
Then emigrate the lymph node and differentiate into plasma cells that migrate to bone marrow
how to plasma cells leave the lymph node
efferent lymphatic vessels
what do plasma cells do
what do memory cells do
Plasma cells - produce antibodies
Memory cells - APC in secondary immune response
Primary immune response
- First injection
- Naive B cell
- Activated B cells
- Antibody secreting cells in peripheral lymphoid tissues - plasma cells
- IgM production
- Long lived plasma cells in bone marrow
- Memory B cell
Secondary immune response
- Second injection
- Memory B cells
- Antibody secreting cells –> plasma cells
- IgG production
- Long lived plasma cells in bone marrow
- Memory B cell
differences between primary and secondary immune response
Primary - IgM, lower antibody production, slower antibody production
Secondary - memory B cells, IgG, higher antibody production, faster antibody production
Effector mechanisms of antibodies - bacterial toxins
- Specific antibody
- Bacterial toxins
- Cells with receptor for toxins
- Neutralization
- Ingestion by macrophage
Effector mechanisms of antibodies - bacterial in extracellular space
- Specific antibody
- Bacteria in extracellular space
- Macrophage
- Opsonization
- Macrophage with Fc receptor
- Ingestion and lysis by macrophage
Effector mechanisms of antibodies - Bacteria in plasma
- Specific antibody (IgM or IgG)
- Bacteria in plasma
- Complement activation - classical pathway
- Complement fragmentation
- Ingestion and lysis
how is the ability of a receptor to bind to an antigen determined
the shape of its binding site
Shape –> folding of peptide chain –> amino acid sequences
where is the information needed to make proteins, including antigen receptors, located
the gneome
how many antigen binding receptors on B and T cells can mammals express (produce)
up to 10^15 different antigen binding receptors on B and T cells
How many genes to antigen binding receptors use
fewer than 500 genes
How many genes code for the variable region
How many genes code for the constant region
Several genes code for variable region
One gene codes for constant region
what contributes to gene diversity
Gene recombination
Somatic mutation
Gene conversion
Number of constant genes in B cell receptors
5
1 gene codes for IgM 1 gene codes for IgG 1 gene codes for IgE 1 gene codes for IgA 1 gene codes for IgD
how are antigen receptor genes coded
Antigen receptor genes are coded for by 3 genes originating in 3 widely separated groups.
The genes for a complete receptor chain are assembled by joining one gene selected from each group.
Variable genes - hundreds
Joining genes - tens
Constant gene - one
How many distinct light chain loci
2
1 coding for kappa chains
1 coding for lambda chains
these are located on different chromosomes
which antibody is produced first
IgM (mu gene)
which antibodies do all B cells have
IgM (mu gene)
IgD (delta gene)
Which antibody is mainly produced in secondary immune response
IgG (gamma gene)
gene recombination
deleting unwanted genes by looping out
unwanted genes form a loop that is then cut off by a recombinase enzyme and the cut ends are joined together
gene recombination - construction of an immunoglobulin light chain
selected V and J genes are joined as intervening genes deleted
VJ and C genes remain separated until RNA splicing occurs
intervening RNA segments are deleted leaving V, J, and C genes together in the mRNA
DNA rearrangement occurs during early B cell development so each individual B cell is committed to making a single form of light chain for its antigen receptor
gene recombination - heavy chain construction
2 DNA rearrangement events are required to link V, D, and J genes together
first rearrangement event joins selected D and J genes
second rearrangement event adds selected V gene
finally unwanted J genes are excised and VDJ joined to C in the mRNA
Gene recombination - B cell development
during development, each B cell has 4 attempts to make a productive gene rearrangement coding for a functional immunoglobulin
if it fails all 4 attempts - apoptosis
1st attempt - first IGK gene rearrangement
2nd attempt - second IGK gene rearrangement
3rd attempt - first IGL gene rearrangement
4th attempt - second IGL gene rearrangement
How are CDR1, CDR2, and CDR3 formed on immunoglobulin light chain
CDR1 and CDR 2 - formed by somatic mutation or gene conversion
CDR3 - formed by recombination of V and J gene segments
how are CDR formed on TCR
CDR - formed by recombination of V, (D), and J gene segments
no somatic mutation
what is the major difference between the variable regions of the TCR and immunoglobulins
formation of CDRs
immunoglobulins have 3 CDRs
CDR1 and CDR2 - somatic mutation
CDR3 - gene conversion
TCR - somatic mutation is stringently avoided to prevent self reactivity
why is somatic mutation avoided in variable region of TCR
to prevent self reactivity
selection of somatic mutants
spontaneous mutation during expression of a B cell clone results in development of cells with antigen receptors that differ in affinity for antigen
cells that bind antigen strongly will be more intensely stimulated than cells that bind it weakly
as a result of this selection pressure, the B cell population gradually increases its binding affinity during the course of an antibody response
if a mutation creates a B cell with reduced antigen binding - apoptosis
gene conversion
in this process segments of upstream genes or pseudogenes are inserted into a single V region to generate sequence diversity
where does gene recombination happen in T cell receptor
gene recombination only in variable region
