32 B and T cell receptors Flashcards
is found in the membrane of the helper T lymphocyte, and is necessary for the T cell to identify the antigen (peptide)
CD4
found in the membrane of the cytotoxic T lymphocyte, and is necessary for identification of the antigen (peptide)
CD8
Aka Immunoglobulin (Ig). Shaped like a Y. Contains two antigen binding sites (each for the same antigen), making it divalent. The molecule is flexible, so that the conformation can change when two antigens are bound
B cell receptor
Monovalent lymphocyte receptor (binds a single antigen). This receptor is rigid
T cell receptor
T/F. Both B cells and T cells require the use of coreceptors. Because of this, the binding of an antigen is not sufficient to activate lymphocytes. The coreceptors must also be activated in order for this to occur
True
T/F. When the antigen binds, enough receptors are cross linked (brought together) that they bring the coreceptors together, and within the proximity of the receptors. This is what initiates the lymphocyte response
True
provide the effector functions of the antibody. Other immune cells recognize this region of the antibody and respond to it in various ways
Constant region
allow the antibody to identify (and bind to) a unique antigen
Variable region
allows for the flexibility of the B cell receptor (useful in binding of two antigens at the same time)
Hinge region
Located in the variable regions. These are regions that have undergone a series of either mutations or nucleotide additions and further increase the variability of the antibody molecule and its ability to recognize a variety of antigens
Hypervariable regions
are transmembrane proteins that form a complex with the B-cell receptor, allowing it to generate a signal following recognition of antigen by the BCR (note: these are co-receptors that must be brought together by cross-linking of B cell receptors)
Ig-beta and Ig-alpha
T/F. o Signaling requires clustering of receptors. Receptors are able to signal in conjunction w/ Ig-alpha and Ig-beta
True
Found in the membrane of mature B cells. It binds to iC3b or c3d. This receptor allows the complement system to play a role in B-cell activation and maturation, thus linking the innate immunity to the adaptive humoral immune response.
Signaling form this receptor enhances activity of the B cell
CD21 (CR2 -compliment receptor 2)
The complement is activated when an extracellular antigen is present. The complement system generates ___, which can either stay bound (and form the membrane attack complex) or be proteolytically cleaved and function as an opsonin.
c3b
If the BCR and the ___ coreceptor complex are both activated, B cell activation will be enhanced (as compared to activation from only the BCR or the ___ complex individually)
CD21 (CR2)
The two types of T cell receptor are:
Alpha-beta and gamma-delta receptor types
Receptors function mainly in the mucosal epithelium
Gamma-delta
receptors consists of two subunits (alpha and beta). Both subunits contain a variable region and a constant region.The variable region: allows recognition of the antigen. The constant region: adheres to the cell membrane (attached to the transmembrane domain)
Alpha-beta
Forms part of the co-receptor in the T helper lymphocyte
CD4
Forms the co-receptor in the cytotoxic T lymphocyte
CD8
Found in the membrane of mature T cells. Formed by many proteins. This co-receptor complex is necessary for the cell to respond to receptor activation
CD3 complex
This lymphocyte receptor type cannot recognize antigens in their soluble forms
TCRs
1) A dendritic cell eats a pathogen
2) Part of the pathogen goes to the surface of the dendritic cell
3) The dendritic cell travels to the spleen and lymph nodes and presents the antigen to a helper T cell on its MHC complex
4) The helper T cell is then activated
Antigen presentation
During an intracellular viral infection. Peptides are generated in the cytosol. These peptides will be loaded in the MHC ___ complex. This allows cytotoxic T lymphocytes to recognize infected cells of our body
MHC I complex
During an extracellular infection, Pathogens (esp. bacteria) must be degraded by antigen presenting cells. These cells then present the pathogenic peptides on their MHC ___ complexes, at which point T helper cells identify the antigen and mediate the immune response
MHC II complexes
o Composed of three alpha subunits, one beta subunit, and a transmembrane domain. Found on the surface of all nucleated cells, and “professional antigen presenting cells”
MHC I molecule
1) Viral proteins are synthesized, and subsequently targeted for ubiquitination
2) The viral protein is degraded in the proteasome
3) Viral peptide remnants are transported to the ER by TAP proteins
4) Once in the ER, the cell loads the MHC I molecule (which is synthesized in the ER and resides there) with the viral peptide
5) The MHC I molecule is then transported to the cell membrane through the standard secretory pathway (golgi –> exocytic vesicle–>membrane). Here the MHC I complex presents the antigen to CD8+ cells
MHC I pathway of antigen processing and presentation
A sign of SCID, increased susceptibility to viral infections. Mutations: TAP protein. Results in an inability to display antigens on class I MHC proteins. This results in a deficient adaptive immune system (the innate immune system is spared)
MHC I deficiency (Bare lymphocyte syndrome) type I
Protein that functions to transport viral peptide remnants from the cytosol to the ER
TAP proteins
o Composed of two alpha subunits, two beta subunits, and a transmembrane domain
o Only present in professional antigen presenting cells (macrophages, dendritic cells, B cells). Presents antigens to T helper cells
MHC II molecule
o Used for dealing w/ extracellular infections
1) Extracellular proteins are engulfed by phagocytosis (into the professional antigen presenting cell)
2) Proteins are degraded to peptides in the lysosome (to kill the organism and/or present the peptides)
3) The MHC II molecule (synthesized in the ER and residing there as well) is transported to the endosome containing the foreign peptide (MHCII complex travels from ERgolgiexocytic vesicleexocytic vesicle fuses w/ the endosome –or recycling endosome- that contains the foreign peptide)
4) Association of foreign peptides w/ MHC II complex occurs in the recycling endosome, which then transports the loaded MHC II complex to the membrane of the professional antigen presenting cell
MHC II pathway for antigen process and presentation
Signs of SCID, increased susceptibility to bacterial infections. Mutations resulting in the inability to synthesize a transcription factor required for the synthesis of the mRNA for the MHC II complex
Bare lymphocyte syndrome (type II)
Which cells express both MHC class I and class II proteins on their membranes?
Professional Antigen Presenting Cells
The only professional antigen presenting cell that presents the antigen to naïve T cells in the spleen and the cortex of the lymph nodes (results in clonal expansion and differentiation into effector T cells)
Dendritic cells
T/F. Dendritic cells migrate to the lymph nodes and spleen after an infection to present foreign peptides to naïve T cells. The T cells must then be given further instruction at the site of the infection
True
Only present antigens to experienced T cells. Communicates to the T cells that have been recruited to the site of infection, that the infection is still present, and that it is okay for the T cells to perform their function. Note: These cells do not migrate to the lymph nodes. This cell is a resident of the tissues
Macrophages
: Effector T cell activation of a macrophage increases its ability to kill microorganisms
Activated macrophages
T/F. B cells only present antigens to inexperienced T cells
False. B cells only present antigens to experienced T cells
Effector T cell activation of B cells enables the B cells to secrete antibodies (humoral immunity)
Activated B cells
This cytokine stimulates MHC II and MHC I expression in APCs, enhancing their capacity to present antigens. It is secreted by NK cells (among others) and enhances the activation of CD4+ cells and CD8+ cells
IFN-gamma
Stimulates MHC I and type I interferon expression in APCs (enhances the activation of CD8+ cells)
IFN-gamma
activate a large number of T cells w/o the need for antigen processing. Note: This response is not specific for any antigen. It causes a polyclonal expansion of T cells that is not effective against any particular pathogen
Superantigens
T/F. The heavy and light chains of the Ig are encoded on different chromosomes
True
This part of the Ig has the V, D , and J regions, as well as a constant region (C)
Heavy chain
This part of the Ig has the V, J, and C subregions.
Light chain
o If the combination of segments is viable (i.e. functional, no premature stop codons present, etc), the receptor migrates to the plasma membrane and silences the other allele
Allelic exclusion
Either the kappa or the lambda locus is expressed to produce the light chain
Isotype exclusion
These genes are responsible for the DNA rearrangement seen in VDJ recombination
RAG (recombination activation gene) 1 and 2
1) Stem cell
2) Rearrangement of the heavy chain segments occurs
3) Heavy chain travels to membrane and signals proliferation (of chain), allelic exclusion, and continuation of B cell maturation
4) Generation of the light chain occurs
5) Markers for mature B cell are IgM and IgD
6) When the mature B cell is activated, IgM is the Ab that is predominantly secreted. However, the B cell can change which Ab it is secreting
Stages in the life of a B cell
Nucleotide transferase protein. Creates the hypervariable regions. Mainly in the heavy chain, performs addition or deletion of nucleotides where segments join to form very diverse regions
TdT (Terminal deoxynucleotidyl transferase)
Is the CD19 coreceptor found in the B or T lymphocyte?
CD19 is found in the membrane of B lymphocytes
A gene pool w/ multiple V, D, and J segments (just like the BCR)
VDJ recombination
Nucleotide addition in all chains
Multiple possibilities of combinations of heavy and light chains
All contribute to:
A diverse TCR repertoire
T/F. The T cell receptors are encoded in the human TCR beta and alpha chain loci
True
o Affects both B and T cell responses (normal levels, affected function)
o Low levels of serum Ig
o Compromised immune system: recurrent infections in early infancy (bacteria, viruses, fungi, protozoa)
o X-linked (75% of cases): Interleukin-2 (IL-2) receptor subunit (same chain in IL-7)
o Autosomal recessive: deletion or loss of function mutations in RAG-1 or RAG-2; ZAP-70 (signal transduction of TCR); adenosine deaminase (ADA, purine metabolism)
SCID
T/F. T cells can only identify processed peptides (only proteins) whereas B cells can recognize any antigen in its soluble form (carbohydrates, proteins, lipids and nucleotides). This is b/c the T cell can only recognize peptides that are presented on the MHC complex
True
The cytotoxic T lymphocytes only recognize peptides that are presented via MHCI. T helper cells only recognize peptides that are presented via MHCII. Note: Memorization tip –the multiplication should always equal 8
MHC restriction
The gene encoding production of the MHC complexes
HLA gene
Any cell that has the ability to present antigens to both T helper and cytotoxic T lymphocytes. As supposed to cells that can only present antigens to cytotoxic T lymphocytes through their MHCI complex
Professional Antigen presenting cells (APCs)
This is a very important cytokine for macrophages. It is secreted by NK cells at the site of infection. It increases the capacity of the macrophages to present an antigen to CD4+ and CD8+ cells
IFN-gamma
