2.1 Main immunological definitions

Question 1

Adjuvant

Answer 1

Agents that increase the stimulation of the immune system by enhancing antigen presentation (depot formulation (remains longer), delivery systems) and/or by providing co- stimulation signals (immunomodulators). Aluminium salts are most often used in today’s vaccines. Especially important in protein-based vaccines because if you did not use an adjuvant it would have a weak IR because our IS needs a second danger signal to be activated, by DAMPS or pathogens. The adjuvant gives co-stimulation.

Question 2

Affinity

Answer 2

tendency of an antibody to bind to a specific epitope at the surface of an antigen

Question 3

Avidity

Answer 3

sum of the epitope-specific affinities for a given antigen. It directly relates to its function

Question 4

Affinity Maturation

Answer 4

Processes through which antigen-specific B cells undergo somatic hypermutation and affinity based selection, resulting in B cells that produce Ab w/ increased affinity over germline Ab.

Question 5

Antibodies

Answer 5

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.

Question 6

Antigen-Presenting Cells

Answer 6

Cells that capture antigens by endocytosis or phagocytosis, process them into small peptides, display them at their surface through major histocompatibility complex (MHC) molecules, and provide costimulation signals that act synergistically to activate antigen-specific T cells. APCs include B cells, macrophages, and dendritic cells, although only dendritic cells are capable of activating naïve T cells.

Question 7

B Lymphocytes

Answer 7

Cells that originate in the bone marrow, mature in secondary lymphoid tissues, become activated in the spleen/nodes when their surface immunoglobulins bind to an antigen, and differentiate into antibody secreting cells (plasma cells) or memory B cells.

Question 8

Carrier Protein

Answer 8

A protein that is used as a template to which polysaccharide moieties are chemically conjugated to generate glycoconjugate vaccines. It is believed that carrier proteins provide antigenic epitopes for recognition by CD4+ T-helper cells, in particular follicular T-helper cells. Esp important in polysaccharide vaccines.

Question 9

CD4+ T-helper 1 Lymphocytes

Answer 9

CD4+ T cells that on activation differentiate into cells that mainly secrete interleukin (IL)-2, interferon (IFN)-γ, and tumor necrosis factor (TNF)-β, exerting direct antimicrobial functions (viruses), and essentially providing support to cytotoxic T cells and macrophages.

Question 10

CD4+ T-helper 2 Lymphocytes

Answer 10

CD4+ T cells that on activation differentiate into cells that mainly secrete IL-4, IL-5, IL-6, IL-10, and IL-13, exerting direct antimicrobial functions (parasites) and essentially providing support to B lymphocytes.

Question 11

CD4+ T-helper 17 Lymphocytes

Answer 11

CD4+ T cells that mainly secrete IL-17, IL-21 & IL-22, and are implicated in host defence against extracellular bacteria colonizing exposed surfaces (airways, skin, gut).

Question 12

CD8+ T Cells

Answer 12

Lymphocytes that specialize in the killing of infected cells, through direct contact or cytokine (IFN-γ, TNF-α) production.

Question 12

Central Memory T Cells

Answer 12

Memory T cells traffic through the lymph nodes, ready to proliferate and generate a high number of effector cells in response to specific microbial peptides.

Question 13

Chemokines

Answer 13

Small secreted proteins that function as chemoattractants, recruiting cells that express the corresponding chemokine receptors at their surface and thus migrating toward higher concentrations of chemokines.

Question 14

Costimulatory Molecules

Answer 14

Molecules that become expressed at the surface antigen-presenting cells on activation and deliver stimulatory signals to other cells, namely T and B cells.

Question 14

Dendritic Cells

Answer 14

Cells that constantly sample their surroundings for pathogens such as viruses and bacteria, detect dangers, and initiate immune responses. Immature patrolling dendritic cells (DCs) have high endocytic activity and a low T-cell activation potential. Contact with a pathogen induces maturation and the expression of certain cell-surface molecules, greatly enhancing their ability to activate T cells.

Question 15

Extrafollicular Reaction

Answer 15

B-cell differentiation pathways that occur outside of germinal centers in response to protein or polysaccharide antigens. Extrafollicular reaction is rapid, generates B cells that are short-lived (days), and produces low-affinity antibodies without inducing immune memory.

Question 16

Effector Memory T Cells

Answer 16

Memory T cells patrol through the body to detect specific microbial peptides and are capable of an immediate cytotoxic function in case of recognition

Question 17

Follicular Dendritic Cells

Answer 17

Stromal cells in the spleen and nodes that on activation express chemokines (notably CXCL13) to attract activated antigen-specific B and T cells and thus nucleate the germinal center reaction. Follicular DCs provide antiapoptotic signals to germinal center (GC) B cells and support their differentiation into plasma cells or memory B cells.

Question 18

Follicular T-helper Lymphocytes

Answer 18

CD4+ T cells that on activation migrate toward follicular DCs and provide critical help to germinal center B cells, influencing isotype switching, affinity maturation, and differentiation

Question 18

Germinal Centers

Answer 18

Dynamic structures that develop in the spleen/nodes in response to an antigenic stimulation and dissolve after a few weeks. GCs contain a monoclonal population of antigen-specific B cells that proliferate and differentiate through the support provided by follicular DCs and T-helper cells. Immunoglobulin class-switch recombination, affinity maturation, B-cell selection, and differentiation into plasma cells or memory B cells essentially occur in GCs. Sustained stimulation of T and B-cells to generate a good immune response.

Question 19

Isotype Switching

Answer 19

Switch of immunoglobulin (Ig) expression and production from IgM to IgG, IgA, or IgE that occurs during B-cell differentiation through DNA recombination.

Question 20

Marginal Zone

Answer 20

The area between the red pulp and the white pulp of the spleen. Its major role is to trap particulate antigens from the circulation and present them to lymphocytes.

Question 20

Pattern Recognition Receptors

Answer 20

Germline-encoded receptors sensing the presence of infection via the recognition of conserved microbial pathogen-associated molecular patterns and triggering innate immune responses.

Question 21

Regulatory T Cells

Answer 21

T cells that on activation differentiate into cells that express specific cytokines (IL- 10, transforming growth factor [TGF]-β/surface markers) and act to suppress activation of the immune system through various mechanisms, maintaining immune homeostasis and tolerance to self-antigens. You do not want these in the vaccine because you do not want to downregulate the response.

Question 21

Resident Memory T Cells

Answer 21

Effector memory T cells residing in specific tissues (lungs, gut, skin) and conferring an immediate-early line of defense against viral and bacterial pathogens.

Question 21

Somatic Hypermutation

Answer 21

A process that introduces random mutation in the variable region of the B- cell receptor (i.e., 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 antibody diversification.

Question 22

T Lymphocytes

Answer 22

Cells that originate in the thymus, mature in the periphery, become activated in the spleen/nodes if their T-cell receptors bind to an antigen presented by an MHC molecule and they receive additional costimulation signals driving them to acquire killing (mainly CD8+ T cells) or supporting (mainly CD4+ T cells) functions

Question 23

T-Independent B-Cell Responses

Answer 23

Differentiation pathway of B cells, mainly elicited by polysaccharides, that takes place in the marginal zone and extrafollicular areas of the spleen/nodes. Its hallmarks are to be rapid (days), while eliciting the transient (months) production of antibodies of low affinity without inducing immune memory. You do not want this in a vaccine because you have low-affinity, short-lived Ab and you will not induce a good memory. You ideally want a T-dependent response.

Question 24

T-Dependent B-Cell Responses

Answer 24

Differentiation pathway of B cells elicited by protein antigens that recruit T and B cells into GCs of the spleen/nodes. Its hallmarks are to be slow (weeks), while eliciting long-lasting (years) production of antibodies of high affinity and immune memory.

Question 25

Toll-Like Receptors

Answer 25

A family of 10 receptors (TLR1 to TLR10), present at the surface of many immune cells, that recognize pathogens through conserved microbial patterns and activate innate immunity when detecting danger. You want to stimulate these with the adjuvant to have a good IR. You can play around because dependent on which is stimulated you can have a different type or response, a different isotype of Ab or a different Th1 or Th2 type.