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Stages at which Isotype Switching occurs
This will be covered later in the course and is
presented here to provide context to understanding
isotype switching. It will not to be tested in Exam 1
antigen-independent
stem cell
pre-B cell
immature B cell
(IgM +)
mature B cell
(IgM +, IgD +)
antigen-dependent
IgM
isotype switching
IgG
IgE
IgA
Does Isotype Switching occur in one B cell?
1. Activated B cell resides in the Germinal
Center
-some individuals will mature directly into
plasma cells
2. Some B cells in the germinal center divide and
undergo hypermutation and/or isotype
switching
3. After this stage they cannot divide and the
higher affinity ones are selected
4. These cells can mature to plasma cells
5. End result: The B cell makes a different
antibody isotype but with the same specificity
Exception to the one B-cell: One BCR Dogma
One B-cell : Two BCR?
One is self-reactive
Other is pathogen reactive
Why would a B-cell want to express two
BCRs of this type?
The self-reactive BCR can fill a hole in the B cell
repertoire - it might be essential to recognize a
pathogen even though it reacts with self.
Mechanism of Self-tolerance
B-cells with BCR that bind strongly to the
constituents of surrounding bone marrow
tissue are programmed to die - apoptosis
Deficient
Slightly
Immune
overactive
Pathogens=0
Response
Immune
Overactive
Pathogens>0
Pathogens=0
Immune
Response
Response
Immune
Pathogens>>0
Response
Mechanism of Self-tolerance
T-cell Receptor
• Two Types
1) TCR and TCR
T cells
 TCR and TCR
T cells
• Antigen Binding site
- V and V
• Similar to Fab fragment
Functions and Properties of T Cells
• T cells
- Recognize MHC:peptide complex
- Diverse Functions
A) Stimulate other immune cells
B) Cytotoxic - kill infected host cells
- Cell:cell interactions
• T cells
- Dominant T-cell in epithelial tissue
(only 1-5% in circulation)
- Recognizes more than MHC:peptide
- Not well characterized
• Antigen-Recognition
site = Peptide:MHC
Recognition site
• Single V region CDR1-3 for each chain
• All TCRs on a single T
cell are the same
• Different T cells
express different TCRs
• Diversity mechanisms
like BCRs

Figure 3-3
No Ds in Vgene
Occurs in the
Thymus
DJ first then VDJ
in gene
rearrangement

Figure
• -chain locus is
within -chain locus
3-8
• Fewer V segments
then and
• Two D segments can
be incorporated
Functional T-cell
Receptor Complex
• Core complex
• CD3 complex:  , 
• (zeta) chain
• Function of CD3 and :
Transport
Signal Transduction
Invariant Chains
Avidity
Comparison of B and T cells
PROPERTY
B CELLS
T CELLS
Bone Marrow
Thymus
Pre-antigen
Diversity
YES
YES
Post antigen
Diversity
YES
NO
Single antigen
specificity
YES
YES
Variety
Peptide:MHC
Secreted form of
Receptor
Yes
No
Invariant signaling
subunits
Yes
Yes
Initial Development
Antigen recognized
Immunodeficiency diseases
• SCID - severe combined immunodeficiency disease
- Many causes but a rare disease
- Classified according to lymphocyte profile (T B NK)
- Bone Marrow transplant can cure
• Omenn syndrome
- RAG proteins have reduced activity
- Patient is: T+ B- NK+
• CD3 and CD3 deficiency diseases
- Mutations in some CD3 genes
- Patient is: T+/TCR- B+ NK+
or T- B+ NK+
How do T cells recognize antigens?
Antigen Processing
Antigen Presentation
Antigen Presenting Cell (APC)
Professional APC
MHC class I communicates with Tc cells
MHC class II communicates with TH cells
IR to Extracellular Pathogens
(CD4-MHC I)
1. Antibodies needed
2. Pathogen recognition/internalization by
professional APCs
a. B cells
b. Macrophages
c. Dendritic cells
3. Phagolysosome degrades proteins to peptides
4. Peptides:MHC II complex transported to surface
5. Professional APC contacts CD4 T cells
6. CD4 TH cells secrete cytokines to signal B cell
maturation
IR to Intracellular Pathogens
(CD8-MHC II)
1. Antibodies ineffective
2. Pathogen replicates in the cell and proteins are
degraded in the cytoplasm of the cell
3. Peptides are transported into ER and bind MHC I
and transported to the surface
4. MHC I expressing cells present to CD8 T cells
5. CD8 T cells (cytotoxic T cell, CTL) kills host cell
Figure 3-11
Structures involved in MHC Presentation
TCR
CD4 and CD8
MHC1 and MHCII
T cell Co-Receptors
Figure 3-13 part 1 of 2
CD8-MHC I
CD4-MHC II
Closed
Open
Figure 3-15
8-10 amino acids
13-25 amino acids
Degenerate binding specificity
Figure 3-16
Peptide Degradation
and Transport
Proteosome=Shredder
Transporter associated
with antigen processing
Chaperones
Figure 3-19
Prevention of Peptide:MHC II formation in ER
CLIP - class II-associated invariant-chain peptide
Figure 3-21 part 2 of 3
TCR binds MHC and
peptide
Sample Exam Question
Testing allelic exclusion (inherit alleles for each Ig locus; only one
rearranges to produce a heavy or light chain)
Which of the following best describes the process of allelic exclusion?
a. BOTH alleles of the light chain locus (e.g. lambda) rearrange DNA,
but only ONE allele of the heavy chain rearranges DNA
b. BOTH alleles of the heavy chain locus rearrange DNA, but only
ONE allele of the light chain (e.g. lambda) rearranges DNA
c. BOTH alleles of the light chain locus and BOTH alleles of the light
heavy chain rearranges DNA
d. The primary transcript RNA from BOTH alleles of the light chain
and BOTH alleles of the heavy chain is rearranged
e. None of the above
NOT a Sample Exam Question
Testing obscure facts that are probably NOT relevant to your education
How many Diversity segments (DH) are present in the Immunoglobulin
Heavy chain locus?
a. 26
b. 27
c. 3.3 x 106
d. It varies depending on the combinations made with the light chain
e. None of the above