VACCINE DEVELOPMENT : IMMUNOLOGY – THE
BASICS
1: MAIN IMMUNOLOGICAL DEFINITIONS
1.1: VACCINE MEDIATE PROTECTION
- Generate vaccine-mediated protection = complex challenge
- Most currently available vaccines are developed empirically, and we don’t know how they
activate the IS this has changed a lot!
o Mainly we think about antibodies as part of the IS that is crucial to activate this IR,
but not only Abs are important, also cellular immunity plays a role
- Early protective efficacy = primarily conferred by the induction of antigen-specific Abs, but
these Abs are not enough! T-cell mediated responses, cellular immunity, is as equally
important!
- There is more to Ab-mediated protection than the peak of vaccine-induced Ab titers. The
quality of such Ab has been identified as determining factor in efficacy:
o Activity Ab - Specificity Ab - Neutralizing capacity of the Ab
- Long-term protection requires:
1. Persistence of vaccine Ab above protective threshold: stay in serum longtime
a. Protective threshold for viruses is hard to find, it depends on multiple factors
2. Maintenance of immune memory cells capable of rapid + effective reactivation
a. Example: measles vaccines work very good, but for others it declines need a very
good knowledge in order to change this!
b. Memory cells are critical for vaccine efficacy, they don’t avoid infection, but it will be
less severe
- Vaccines activate:
1. Abs mainly look at Abs because it is easy to separate them from blood or test them
2. CD4+ T-cells T-cells are much more complex to study
3. CD8+ T-cells
2: IMMUNOLOGICAL DEFINITIONS
No exam questions about these, but you have to know it!!
Name Definition
Adjuvant Agents that increase the stimulation of the IS by enhancing antigen
presentation (depot formulation, delivery systems) and/or by providing co-
stimulation signals (immunomodulators)
Aluminum salts = most often used!
Ab affinity Refers to the tendency of an Ab to bind a specific epitope at the surface of an
antigen determines the strength of the interaction
Ab avidity Sum of the epitope-specific affinities for a given antigen. It directly relates to its
function
Affinity Processes through which Ag-specific B-cells undergo somatic hypermutation
,maturation and affinity-based selection, resulting in B-cells that produce antibodies with
increased affinity over germline antibodies.
Abs Proteins of the immunoglobulin family, present on the surface of B-
lymphocytes, secreted in response to stimulation, that neutralize antigens by
binding specifically to their surface
Antigen APC = cells that capture antigens by endocytosis or phagocytosis process
presenting cells them into small peptides display them at their surface, through the MHC-
molecules (major histocompatibility complex) = provide co-stimulation signals
that act synergistically to activate Ag-specific T-cells
APC = B-cells, MP, DCs (Only DCs are capable of activating naïve T-cells)
B-cells Cells that originate in the bone marrow mature in secondary lymphoid
tissues become activated in the spleen/LNs when their surface
immunoglobulins bind to an antigen, and differentiate into Ab-secreting cells
(plasma cells) or memory B-cells
Carrier protein Protein used as template to which polysaccharide moieties are chemically
conjugated to generate glycoconjugate vaccines. They can provide antigenic
epitopes for recognition by CD4+ T-helper cells, in particular follicular THC
CD4+ T-helper 1 CD4+ T-cells that on activation differentiate into cells that mainly secrete
lymphocyte interleukin-2 (IL2), IFNy, and TNF (tumor necrosis factor) exerting direct
antimicrobial functions (viruses) and providing support to cytotoxic T-cells and
MPs
CD4+ T-helper 2 CD4+ T-cells that on activation differentiate into cells that mainly secrete
lymphocytes IL4/5/6/10/13 exerting direct antimicrobial functions (parasites) and
providing support to B-lymphocytes
CD4+ T-helper CD4+ T-cells that mainly secrete IL17/21/22 and are implicated in host defense
17 Lymphocytes against EC bacteria colonizing exposed surfaces (airways, skin, gut)
CD8+ T-cells Lymphocytes specialized in killing of infected cells, through direct contact, or
cytokine (IFNy, TNFa) production
Central memory Memory T-cells traffic through the LNs, ready to proliferate and generate a high
T-cells nr of effector cells in response to specific microbial peptides
Chemokines Small secreted proteins that function as chemoattractant, recruiting cells that
express the corresponding chemokine-receptors at their surface and thus
migrating toward higher concentrations of chemokines
Costimulatory Molecules that become expressed at the surface of APCs on activation
molecules deliver stimulatory signals to other cells, namely B- and T-cells
Dendritic cells Cells that constantly sample their surrounding for pathogens (viruses, bacteria,
and detect danger) initiate immune responses. Immature patrolling DCs =
high endocytic activity and low T-cell activation potential. Contact with
pathogen induces maturation and expression of certain cell-surface
molecules, enhancing their ability to activate T-cells
Effector Memory T-cells patrol through the body to detect specific microbial peptides
memory T-cells and are capable of an immediate cytotoxic function in case of recognition
Extrafollicular B-cell differentiation pathways that occur outside of the germinal centers, in
reaction response to protein or polysaccharide antigens. Extrafollicular reaction = rapid,
generates B-cells that are short-lived (days), and produces low-affinity Abs
without inducing immune memory
Follicular DCs Stromal cells in the spleen and LNs that on activation express chemokines
(CXCL13!) attract activated antigen-specific B- and T-cells and thus nucleate
the germinal center reaction. Follicular DCs provide anti-apoptotic signals to
, germinal center (GC) B-cells and support their differentiation into plasma cells
or memory B-cells
Follicular T- CD4+ T-cells activated migrate toward fDCs: provide critical help to germinal
helper center B-cells, influencing isotype switching, affinity maturation and
lymphocytes differentiation
Germinal center Dynamic structures that develop in the spleen/LNs, in response to antigenic
stimulation & dissolve after few weeks. GCs contain a monoclonal population of
antigen-specific B-cells that proliferate and differentiate through the support
provided by fDCs and T-helper cells. Immunoglobulin class-switch
recombination, affinity maturation, B-cell selection, and differentiation into
plasma cells or memory B-cells = all happens essentially in GCs
Isotype Switch of Ig expression and production from IgM > IgG/A/E that occurs during
switching B-cell differentiation through DNA recombination
Marginal zone Area between the red and white pulp of the spleen. Its major role = trap
particular antigens from the circulation present them to the lymphocytes
Pattern Germline-encoded receptors sensing the presence of infection via the
recognition recognition of conserved microbial pathogen-associated molecular patterns and
receptors triggering innate IRs
Regulatory T- T-cells that when activated differentiate into cells that express specific
cells cytokines (IL10, TGFB/surface markers) and act to suppress activation of the
immune system through various mechanisms, maintaining immune
homeostasis and tolerance to self-antigens
Resident Effector memory T-cells residing in specific tissues (lungs, skin, gut)
memory T-cells conferring an immediate-early line of defense against viral and bacterial
pathogens
Somatic Process that introduces random mutation in the variable region of the BCR
hypermutation (immunoglobulin) locus at an extremely high rate, during B-cell proliferation.
This mechanism occurs through the influence of the activation-induced cytidine
deaminase enzyme and generates Ab-diversification
T-lymphocytes Cells that originate in the thymus mature in the periphery become
activated in the spleen/LNs if their TCRs bind to an antigen presented by MHC
and they receive co-stimulation signals driving them to acquire killing (mainly
CD8+) or supporting (CD4+) functions
T-cell Differentiation pathway of B-cell, mainly elicited by polysaccharides that takes
independent B- place in the marginal zone and extrafollicular areas of the spleen/nodes.
cell response Hallmarks = be rapid (days), while eliciting the transient (months) production of
Abs of low affinity without inducing immune memory
T-dependent B- Differentiation of B-cells elicited by protein antigens that recruit B- and T-cells
cell response into GCs of the spleen/LNs. Hallmarks = be slow (weeks), while eliciting long-
lasting (years) production of Abs of high affinity and immune memory
Toll-like A family of 10 receptors (TLR1-10), present at the surface of many immune
receptors cells, that recognize pathogens through conserved microbial patterns and
activate innate immunity when detecting danger.
