Adaptive Immunity
INTRO
There are 2 main defenses in adaptive immunity:
● B cell immunity (antibodies) → important against extracellular pathogens
● T cell immunity → important against intracellular pathogens
○ Helper T cells (Th cells; CD4+ T cells), and Cytotoxic T cells (CTL; CD8+ T cells)
Describe the kinetics of a primary vs. memory immune response
The adaptive immunity is more efficient with re-exposure to an identical pathogen; larger AND faster response
● In the first exposure, that pathogen must reach a certain threshold in order for your adaptive immune
response to be triggered → eventually you end up with immunological memory
● In the 1st exposure, the newly developed naive cells are the ones that respond by binding to the pathogen
○ This primary exposure leads to the development of effector cells and memory B & T cells
● For all subsequent exposures, memory cells are the ones responding, and you develop more memory cells
● Immunological memory is the basis for vaccination
● Key features of adaptive immunity are memory and specificity
Innate immunity is always triggered first whenever exposed to a pathogen; it's the first line of defense
● If innate immunity can destroy the pathogen, you may not need to trigger adaptive immunity at all
State the primary lymphoid tissues important in B cell and T cell development
The adaptive immune system involves lymphoid tissues
● B cells and T cells develop as lymphocytes in
primary lymphoid tissues (Bone marrow - B, T;
Thymus - T cells only)
● They always start with the hematopoietic stem
cell becoming a lymphoid progenitor cell in bone
marrow
● B cells develop in bone marrow; the LP cell
undergoes differentiation, enters into
circulation as naive B cell
● T cells develop in the bone marrow and thymus; the lymphoid progenitor cell will enter into the thymus
(now called thymocytes), which express a CD4 and CD8 molecule
○ These thymocytes will undergo more differentiation, and enter circulation either as CD4+ T cell
(naive helper T cell) or as a CD8+ T cell (naive cytotoxic T cell)
The thymus is large in infants and children, when T cell development is highest
● Newborns have very little adaptive immunity because they are still developing the T cells
● The thymus begins to shrink at puberty, but T cell development continues to occur throughout life
● An elderly person is producing much dewar T cells than children, which is why they are immunocompromised
State the importance of each type of secondary lymphoid tissue in adaptive immunity
Secondary lymphoid tissues are where naive T cells and B cells meet and bind to a pathogen
● This is where adaptive immunity is initiated; Naive T and B cells are circulating through the SLTs
● This leads to the generation of effector cells and memory cells
● Our SLTs include: lymph nodes, spleen, Mucosa-Associated Lymphoid Tissues (MALT)
Lymphatic system
● Blood exits the heart via arteries and returns back via veins, meeting at capillaries
● The high blood pressure flow through arteries meets the tiny capillaries, which leads plasma to exit from
the blood and enter into the tissues
● The plasma that has entered tissues via capillaries is called interstitial or tissue fluid
● This fluid enters into lymphatic vessels, and is now called lymph, which is what filters through lymph nodes
Lymph is present throughout tissue, commonly beneath the epithelial cell layer
● It removes waste products from tissues; e.g. dead cells, CO2, pathogens
● If peripheral tissue is infected, lymph transports pathogens to a regional lymph node, where AI is initiated
Lymph node filters lymph; this is the site where B and T
cells encounter lymph borne pathogens
● In here, there are distinct T cell and B cell zones,
where they meet and respond to pathogens
● The B cell zone includes 2 distinct areas: the B
cell follicle and the germinal center
● Naive cells encounter to pathogens here, while
effector cells go back to the infected tissue to
attack it
With a vaccine, the injected microbe is transported to the
regional lymph node via the lymph
● Vaccines are usually injected into the muscle,
subcutaneous tissue, or the intradermal tissue
● Because you get vaccines in the arm, the microbe will be transported to the lymph node in the armpit
Spleen filters blood, and is where B cells and T cells will encounter blood borne pathogens
● There are also distinct sites for B and T cells, and the B cell zone has a B cell follicle and a germinal center
MALT is where B and T cells meet pathogens in mucosal areas
● I.e. it is found in oral-pharyngeal cavity, gastrointestinal, respiratory, urogenital tracts
● MALT are located in tonsils, lungs, colon, appendix etc.
● Pathogens are transported into MALT via special epithelial cells called Microfold cells (M cells)
● The MALT tissues are very tightly packed with cells, and located right below the epithelial cell layer
● A majority of pathogens invading the body do so through mucosal areas
In childhood, tonsils are often swollen due to infections from many first time pathogens
● So, the tonsils are readily removed, but does a tonsillectomy compromise immunity?
● Debatable; some say yes, others say no we have other lymphoid tissue like the adenoids
Define the structure of B cell and T cell receptors
T and B cells express surface receptors that recognize and bind to a pathogen
● Both receptors have a constant region, and a variable region (which is what binds to a pathogen)
● A B cell receptor is an immunoglobulin molecule,
and has 2 identical heavy and light chains
○ Its variable region constitutes the end of
both the light chain and heavy chain
○ Because they’re 2 identical chain, they’re
expressing 2 identical variable regions
● A T cell receptor has one alpha and one beta chain
○ It expresses 1 variable region comprised
of the end of both the alpha and beta
chain
Define the terms: antigen, epitope, clonal expansion
An antigen is any substance that the variable region of a BCR/TCR can bind to
● A microbe expresses many copies of its own unique antigens
● E.g. the influenza virus has 2 distinct antigens: a hemagglutinin antigen, and a neuraminidase antigen
Antigens can be self molecules (i.e. not restricted to microbes)
● E.g. Tissue type is based on expression of human leukocyte antigens
● E.g. Blood type is based on expression of A, B, Rh antigens on RBCs
PAMPs and antigens are similar but different
● One PAMP is expressed by a wide variety of pathogens, and is recognized by PRRs expressed by phagocytes
● One antigen is unique to a specific pathogen, and is recognized by the variable region of a TCR/BCR
An epitope is a molecule on the surface of an antigen, and is unique to that antigen
● An antigen expresses multiple copies of different epitopes
● The variable region of a BCR/TCR binds to one unique epitope based on structural fit
● Our own tissues also expresses epitopes, which may be similar in structure to pathogenic epitopes
○ This is how we could get autoimmune diseases
● A BCR directly binds to an epitope expressed by antigens
● A TCR requires other cells to present an epitope to it (needs a major
histocompatibility complex)
● BCR and TCR epitome specificity arises from the random rearrangement
of variable region genes
Every naive B and T cell expresses many copies of its own unique BCR and TCR with specificity for one unique epitope
● This is the basis for specificity in adaptive immunity
Once that B or T cell binds its specific epitope, it undergoes clonal expansion; resulting in many identical cells
● The daughter cells become effector cells and memory cells