Adaptive immune response Flashcards
B Lymphocytes
Are the source of circulating antibodies
T Lymphocytes
recognize peptides from pathogens presented by MCH molecules on infected cells or antigen-presenting cells
Antibody structure
composed of two identical heavy chain and two identical light chain polypeptides, where the variable region combine and form an antigen-binding site that dertermines antigen specificity.
Draining lymph notes
Periphereal lymphoid organs in which the free antigen and antigen-bearing dendritic cells activate antigen-specific lymphocytes, which leads to proliferation and differentiation whereafter most antibodies leave as effectors
M cells
specialized epthelial cells, collect antigens from the epithelial surfaces of the gastrointestinal tract
Paratope
region of antibody that recognizes and binds to the epitope of an antigen. Paratope are produced by the complementary binding of light and heavy chains that create a three-dimensional structure.
Idiotope
The antigenic determinants (epitopes) that are unique to a particular immunoglobulin, one that is directed against a particular antigen and is produced by a clone of cells, or unique to a T-cell receptor
Haptens
small antigens that can only stimulate production of anti-hapten antibodies when linked to a protein
Avidity
describes the measure of overall or accumulated strength of a protein-protein complex, i.e. The total strength of all the non-covalent interactions between an antibody binding to its ligand/s
MHC class I antigen
Resides on the surface of cells and recognizes peptides, 8-10 amino acids long. It is recognized by CD8 cytotoxic T-cells
MHC class II antigen
Resides in endosomes inside the cell and recognizes peptides 13 amino acids or longer. It then travels to the cell surface and is recognized by CD4 T-cells, which activates other cells
Antigenicity
the capacity of viruses to bind to specific antibody molecules
TCR co-receptors
CD4 and CD8 are important in the activation of T cells, primarily because of their ability to interact with the proteins of the MHC, enhancing recognition of the MHC–peptide complex by the T cell receptor (TCR)
CDRs
Hypervariable regions that interact with antigen (V-type)
RSS (recombination signal sequences)
Noncoding DNA sequences, that are found adjacant to the point at which recombination takes place of the antigen receptor loci and designate them for use by the RAGs
RAG-1 and RAG2
Proteins encoded by the recombination-activating genes RAG-1 and RAG-2, which form a dimer that initiates V(D)J recombination
Somatic hypermutation
Mutations in V-region DNA of rearranged immunoglobin genes that produce variant immunoglobins, for higher affinity binding to antigen. Affacts somatic cells exclusively
Class Switch
Somatic gene recombination in activated B-cells that replace one heavy-chain constant region with a different isotype, switching the isotype from IgM to the production of IgA, IgG and IgE (changes antibody effector)
V-region assembly
the variable region is a complete light-chain exon constructed from a variable (V) and a joining (J) gene segment in the genomic DNA.
Junctional diversity
Variability in sequence present in antigen-specific receptors that is created during the process of joining V, D and J gene segments, due to imprecise joining and insertion of nontemplated nucleotides at the joins between segments
Transcriptional activation
required to turn on the expression of genes in a eukaryotic cell. Activators bound to the enhancer can facilitate either the recruitment of RNA polymerase II to the promoter or its elongation
12/23 rule
Gene segment flanked by an RSS with a 12-bp spacer typically can be joined only to one flanked by a 23-bp spacer RSS
Class switch recombination
nonhomologous DNA recombination that is guided by stretches of repetitive DNA known as switch regions (lie in the intron between Jh gene segments and Cmhy gene. changes isotype.
Membrane vs secreted form (IgG’s)
membrane-bound form of Igs function as a BCR controlling maturation, activation, and differentiation of B cells, whereas the soluble secreted Igs, also known as Abs, contribute to the body’s immune surveillance mechanism through pathogen recognition and organization of immune reactions
IgM, IgD expression on surface
All naive B cells
VDJ recombination
Recombination og different gene segments into sequences encoding complete protein chains of immunoglobins and T-cell receptors
Self-antigen
Potential antigen on the tissue of an individual against which an immune response is not usually made except in the case of autoimmunity
AID (activation-induced cytidine deaminase)
Enzyme that initiates somatic hypermutation and isotype switching by deaminating DNA directly at cytosine in immunoglobin V regions or switch regions.
Ku70/Ku80
DNA repair protein required for immunoglobin and T-cell receptor gene rearrangement (double-strand break repair)
four main processes that generate the diversity in the lymphocyte repertoire.
1) Different combinations of V, D and J
2) Different combination of assembly of heavy and light chain, beta and alpha
3) P and N nucleotides, the P nucleotide arise from the cut of the artemis in the proximity of the hairpin structure (palindrome).
4) Somatic hypermutation (B-cell only)
Gene conversion
specific type of homologous recombination that involves the unidirectional transfer in the expressed rearranged V-region gene are replaced with sequences from an upstream V gene segment pseudogene
secondary diversification
- Somatic hypermutation and gene conversion, higher affinity and specificity
- Class switching recombination changes the effector function
Cyclic reentry model
explanation of B-cell behavior in lymphoid follicles, where B-cells in germinal centers lose and gain expression of chemokine receptor CXCR4 and move from light and dark zones
MAIT cells
gammadelta T-cells with limited diversity present in mucosal immune system, that responds to bacterially derived folate derivates presented by nonclassical MHC class Ib molecule MR1
Cross-presentation
Process by which proteins taken up by dendritic cells gives rise to peptides presented by MHC class I molecules. Enables antigens from extracellular sources to activate CD8 T cells
antigen processing
Intracellular degradation of foreign proteins into peptides that can bind MHC molecules for presentation to T-cells
antigen presentation
Display of antigen on the surface of a cell in the form of peptide fragments bound to MHC molecules.
iNKTs
Type of innate-like lymphocyte that carries T-cell receptor with an invariant alpha and beta chain of limited diversity that recognizes glycolipid antigens presented by CD1 MHC class Ib molecules
Allelic exclusion
restricted expression of the individual chains of the antigen receptor genes, such that each individual lymphocyte produces immunoglobin or T-cell receptors of a single antigen specificity.
Positive selection
Process in which developing T-cells whose receptors can recognize antigens presented by self MHC molecules can mature
Negative selection
Process in which self-reactive thymocytes are deleted from the repertoire during T-cell development in thymus
B-cell development
start as common lymphoid progenitor cells, then become early pro-B cells, then late pro-B cells, then large pre-b cells, then small pre-B cells, and finally immature B cells.
T- cell development
The lymphoid progenitor cell goes into the thymus through the cortico-medullary junction. DN thymocytes (CD4−CD8−) migrate across the subcapsular region and then the outer cortex. Interaction between DN cells and cTECs generates DP thymocytes (CD3+CD4+CD8+). Positively selected thymocytes interact with mTECs to complete the maturation process. In the medulla, self-reactive thymocytes are deleted, SP (CD3+CD4+or CD3+CD8+) thymocytes are generated, and, eventually, the export of mature T cells from the thymus takes place.
Isotypic exclusion
Process by which only one allele of a gene is expressed while the other allele is silenced
central tolerance
Immunological tolerance to self antigens that is established while lymphocytes are developing in central lymphoid organs
Receptor editing
replacement of a light or heavy chain of a selfreactive antigen receptor on immatur B-cells with a newly rearranged chain that does not confer autoreactivity
Peripheral tolerance
state of unresponsiveness of the immune system to substances or tissue, by mature lymphocytes in peripheral tissues
double negative thermocytes
Immature T-cells in the thymus that lack exression of the two co-receptors CD4 and CD8 and represent the progenitors to the remaining T-cells developing in thymus
double-positive thermocytes
Immature T-cells in the thymus that exress CD4 and CD8 co-receptor proteins
dendritic epidermat T cells
Dendritic epidermal T cells (DETCs) expressing invariant Vγ5Vδ1 T-cell receptors (TCRs) play a crucial role in maintaining skin homeostasis in mice. When activated, they secrete cytokines, which recruit various immune cells to sites of infection and promote wound healing.
Type 1 immunity
Effector activities aimed at elimination of intracellular pathogens
Type 2 immunity
effector activities aimed at elimination of parasites and promoting barrier and mucosal immunity
Type 3 immunity
effector activities aimed at elimination of extrecellular pathogens (bacteria and fungi)
extrinsic pathway
Signaling pathway triggered by extracellular ligands binding to specific cell-surface receptors, which leads to apoptosis
Intrinsic pathway
Signaling pathway that mediates apoptosis in response to noxious stimuli, initiated by mitochondrial damage
follicular dendritic cells (FDCs)
cell type of uncertain origin in B-cell follicles of peripheral lymphoid organs that capture antigen/antibody complexes using non-internalized Fc receptors and present them to B-cells for internalication and processing during germinal center reaction
fibroblast reticular cells (FRCs)
Lymph node stromal cell found in the T-cell zone of lymph node cortex. Creates networks of collagen-rich reticular fibers that guide DCs, T lymphocytes and B lymphocytes in lymphoid tissue
homing
dirction of a lymphocyte into a particular tissue
Conventional dendritic cells (cDCs)
dendritic cells that mainly participates in antigen presentation to, and activation of naive T-cells
FcRn recycling
Stability based n recycled mechanism via the neonatal fc receptor, binds IgG in endosomes at the pH 6, release antibody into serum and degrades antigen in endolysis.
hybridoma technology
one of the most common methods used to produce monoclonal antibodies. In this process, antibody-producing B lymphocytes are isolated from mice after immunizing the mice with specific antigen and are fused with immortal myeloma cell lines to form hybrid cells
BAFF
B-cell activating factor belonging to TNF family, binds receptors BAFF-R and TACI to promote B-cell survival
APRIL
TNF family cytokine related to BAFF, that binds receptors TCAI and BCMA on B-ells to promote survival and regulate differentiation
TI-1 antigens
Antigens that can elicit antibody production without involvement of T-cells. TI-1 have intrinsic B-cell activating activity
TI-2 antigens
Antigens that can elicit antibody production without involvement of T-cells. TI-2 activate B-cells by having multibple identical epitopes that cross-link the B-cell receptor
Germline center
Site of intense B-cell proliferation and differentiation that develop in lymphoid follicles during adaptive immune response
B1 B-cells
self-renewing B-cells found mainly in peritoneal and pleural cavities, have much less diverse antigen-receptor repitoire then conventional B-cells
Marginal B-cells
unique population of B-cells, which do not circulate and distinguished from conventional B-cells by a distinct set of surface proteins
macrophage subcapsular sinus
first layer of immune cells that are exposed to the metastatic tumor cells and tumor-derived antigens coming from the afferent lymphatic vessels
NK cell
ILC important in innate immunity to virusses and other pathogens and in antibody-dependent cell-mediated cytotoxicity- Express activating and inhabitory receptors but not antigen specific receptors of T- or B-cells
Group 1 ILC
generate IFN-gamma in response to activation by cytokines, in particular IL-12 and IL-18, made by DCs and macrophages. Against infection by vira and intracellular pathogens
Group 2 ILC
Produce cytokines IL-4, IL-5 and IL-13 in response to cytokines, particular TSLP, IL-25 and IL-33. Function in promoting mucosal and barrier immunity and aid protection against parasites
Group 3 ILC
responds to cytokines IL-1beta and IL-23 and produce cytokines, including IL-17 and IL-22, which increases defenses against extracellular bacteria and fungi.
Immune module cytotoxic
NK-cells and CD8 T-cells
Immune module type 1
Th1 cells play important roles in the identification and eradication of intracellular pathogens such as viruses and bacteria. (activates M1 machrophages) CCL2 chemokine attract machrophages to site of infection and induce CD8 CTLs and memory T cells.
Immune module type 2
T helper type 2 (Th2) immune response, characterized by the production of interleukin-4 (IL-4), IL-5 and IL-13, is a critical immune response against helminths invading cutaneous or mucosal sites.
Immune module type 3
Th17 cells are proinflammatory cells that secrete IL-17A, IL-17F, IL-21, and IL-22 and provide immunity to several extracellular pathogens. Increases turnover, produces antimicrobial peptides, increases number of circulating neutrophils and recruits them to site of infection.
Antigenic sin
The preferentially use of immunological memory based on a previous infection when a different version of that foreign pathogen is encountered. Leaves the immune system “trapped” by the first response it has made to each antigen, and unable to mount potentially more effective responses during subsequent infections
Immunological memory
Ability of immune system to respond more rapidly and effectively on a second encounter with antigen
T-cell plasticity
Flexibility in the developmental programming of CD4 T cell such that effector T-cell subsets are not irreversible fixed in their function or trancriptional networks that unpin those functions.
Transdifferentiation
transition of one non-stem cell into another cell type. For T-cells this is often used in the transition of comitted T-cell henotype into another. (eg. Th17 -> Th1)
CD4 T-cells
Co-receptor for T-cell that recognizes peptide antigens bound to MHC II molecules.
CD8 T-cells
Co-receptor for T-cell that recognizes peptide antigens bound to MHC I molecules.
Central memory T-cells
Memory lymphocytes that express CCR7 and recirculate between blood and secondary lymphoid tissue. Require restimulation in secondary lymphoid tissue to become fully matured T-cells
Effector T-cells
T-cells that perform the functions of an immune response.
Effector memory T-cells
Memory lymphocytes that recircuate between blood and peripheral tissues, specialized for rapid maturation into effector T-cells
Resident memory T-cells
non-recirculating memory T cells that persist long term in epithelial barrier tissues, including the gastrointestinal tract, lung, skin and reproductive tract.
Memory B-cells
type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiescent state, sometimes for decades.
Sensitization
Involves class switching to IgE production on first contact with an allergen
Allergen
substance that can cause an allergic reaction
