IMM250 Lecture 9 – Effector T cells
Slide 3 – Adaptive immunity
The adaptive immune system is an antigen specific response driven by lymphocytes that
respond to antigen, which results in the development of immunological memory.
Variable means different types of adaptive immune responses can be generated. The adaptive
immune improves over time whereas the innate immune system goes off at the beginning of an
infection and stops.
White blood cells called B lymphocytes and T lymphocytes make up the adaptive immune
system. B lymphocytes will clonally expand after they are triggered by antigen. The clones are all
identical to the original antigen-specific B cell and will secrete antibodies. T lymphocytes will
clonally expand after they are triggered by antigen. The clones will resemble the initial antigen
responsive cell. The clones will become effector T cells. T cells secrete other molecules such as
cytokines and molecules that can directly kill targets.
Slide 4 – Acquired immunity
Acquired immunity is the combination of a humoral immune response characterized by the
secretion of antibodies and cellular immune response driven by lymphocytes (T cells) and
dendritic cells. Dendritic cells are cells of the innate immune system but are good at triggering
an adaptive immune response. Dendritic cells bridge the innate and adaptive immune system.
In many cases, the humoral immune system is not enough to clear an infection. In many cases,
you also need cell-mediated immunity.
Dr. Watts talked about cell-mediated immunity in response to flu. Vaccines only elicit humoral
immunity, but if we can get a vaccine that can elicit cell-mediated immunity, we would have
good long term protection.
Slide 5 – Adaptive immune responses
Are distinct from innate and non-adaptive phases of immunity, which are not mediated by
o Innate immunity is not driven by a specific antigen but rather a danger signal
o By a process of gene recombination to generate a large array of unique antigen
o This can become disregulated in autoimmune disease
o Once the infection is clear, the antigen-specific lymphocytes will contract and die. The
immune cells cannot be over-represented by a single clone. The majority of the
lymphocytes die off and left with a small population of memory cells.
Slide 6 – Antigens
Antigens are foreign proteins that are displayed by a pathogen recognized
B cells and T cells see these in different ways
Slide 7 – Antigens
Any substance that can bind to a specific antibody.
o They also can be displayed by MHC and recognized by T cells. Epitope: The structural component of the antigen actually recognized by an antibody and
antigen receptor (a.k.a. antigenic determinant).
o It is the way the antigen looks to the BCR or TCR.
Many pathogens display multiple epitopes resulting in a polyclonal immune response.
o Some epitopes are more dominant than the others. We make immune responses to the
Polyclonal response: Response induced by multiple epitopes involves multiple clones of
o During immunization or infection, many types of B cells and T cells respond to the
pathogen because many epitopes displayed by pathogen. The immune response will be
specific and hit different aspects of the pathogen. This is a good way of clearing a
Slide 8 – Poliovirus particle
The blue protein has three epitopes which have a different amino acid sequence so they are
recognized by different T cells.
One of the viral proteins showing several peptides, located on the surface of the virus particle,
has three peptides that can be recognized by T cells. T cells will be specific for the three epitopes
if they are present in your repertoire. You get a polyclonal response to the three epitopes and
the individual epitopes of the pink and yellow protein that then expand.
Slide 10 – B cells and T cells “see” antigens differently
T cell recognizes a linear epitope in the context of MHC. They recognize an antigen by the
variable region of the alpha chain and beta chain domain. T cell receptor only has one binding
site. T cell receptor does not get secreted. T cell always stays at the surface of the T cell.
B cells recognize a conformational epitope generated by the tertiary structure of the protein.
They recognize the conformational epitopes by a unique binding site that is formed by the heavy
and light chain of the variable region of antibody molecule. This confers B cell receptor
specificity. When the B cell is activated, the transmembrane of the antibody molecule is
removed so it can be secreted as a soluble antibody molecule. This is what is detected in the
serum of someone actively fighting an infection or has seen an infection in the past.
B cell antibody molecule sticks to the conformational epitope and eliminates the pathogen using
a variety of mechanisms (complement, accessory cell, etc.).
T cell epitopes are buried inside the pathogen. This is a good way for the immune system to
access protein determinants within a pathogen that do not mutate readily. The surface proteins
of influenza mutate a lot, which is why B cell response is seasonal. B cell response has to change
every time the virus mutates. The internal proteins do not mutate so much or else it would
compromise the fitness of the virus. This is why a vaccine that elicits T cell response for influenza
Slide 12 – Recognition of antigen by T cells
o MHC is present on APC. Dendritic cell are the best APC that we have for presenting
peptide antigen to T cells.
T cell antigens = peptides o APC gets infected with virus. The virus gets chopped up and peptides are made. The
peptides are loaded onto the MHC molecule. The T cell receptor sees the peptide
presented on the surface of the APC through the MHC molecule.
Slide 14 – Virally infected cell
The degraded viral protein are transported to the ER where it gets associated with MHC
(exported out to the surface). This is where recognition takes place with the T cell receptor.
Slide 15 – Clonal selection of antigen-specific T cells
The T cell gets activated. The antigen specific T cell will expand. The antigen specific T cells make
several daughter cells that have the same TCR as the originating T cell. The daughter cells have
the same TCR as the original T cell. They will secrete proteins like cytokines that will help clear
the infection. This is the clonal selection hypothesis.
Slide 18 – Development and diversification of T cells
The TCR is formed by combining a number of gene segments called VDJ recombination. This is a
Slide 19 – T cell receptor (TCR)
The TCR does not have different classes. The TM region allows it to be anchored to the plasma
membrane. The plasma membrane of a lymphocyte is a hydrophobic lipid bilayer. The TM
region of the TCR is hydrophobic.
Slide 20 – T cell co-receptors
o Quaternary structure
o This is important for mediating the signal transmission to the T cell
TCR does not act alone after T cell activation.
TCR has a co-receptor that sits inside the T cell, crosses the TM region and binds to MHC (not
the peptide antigen). This is not a variable protein like the TCR. Everyone has the same co-
receptors. The co-receptors are one of two different kinds. There is a CD4 and CD8 co-receptor.
CD stands for cluster differentiation. A T cell that expresses CD4 behaves differently than a T cell
that expresses CD8. A T cell cannot express both, but only one.
Slide 21 – T cell co-