5. Molecs of Spec Recog I Flashcards
antigen (def)
a molecular structure that can be recognized by lymphocytes
immunogen (def)
subset of antigens that actually induces an immune response in an individual
epitope (def)
antigenic determinant
3 things that determine immunogenicity of an antigen?
- induction of the innate immune system and adjuvants 2. induction of B and T cell collaboration 3. discrimination of self and foreign antigens
T-dependent vs T-indep antigens
T dependent: some protein antigen is required for activation of a helper T cell and then a B cell; T independent: fraction of B cells can recognize a subset of structures (complex polysaccharides or LPS) without T cell help
hapten
How can small, even inorganic, compounds serve as antigens? Such small molecules are called haptens. They do not elicit antibody responses by themselves, but can induce responses if chemically bound to a large protein antigen called carrier. The hapten-carrier complex will induce a response that consists of some antibodies that are specific for the hapten and some that are specific for the carrier. The antibody recognizes the hapten. The carrier is neede to stimulate T-cells which help the humoral response
T cell receptors only recognize ____ epitopes
linear
how do you separate the antigen binding andeffector domains of antibodies/immunoglobulin?
proteolytic cleavage: papain (2 fab and 1 fc) or pepsin (fab2 [both arms together] and 1 fc)….50,000-70,000 Da = heavy chains (so two together are 100,000 to 140,000….27,0000 Da = light chains (so 54,000 for two together)
what does Fab stand for?
fragment antigen binding
what does Fc stand for?
fragment crystallizable (it’s the effecotr portion of the Ab)
what regions of antibodies determine the hypervariability?
CDR (complementarity determining regions) they are portions that are very different, even between two otherwise very closely realted V domains (are hypervariable)
PCN hypersensitivity
Penicillin is a hapten that normally cannot induce an immune response. It is also a drug, however, that binds to plasma proteins (“carrier”) at a certain concentration shortly after administration. While most people are naturally tolerant to their plasma proteins, in some the drug coupled to its carrier induces immune recognition and, typically, IgE production (sensitization). Upon re-exposure to the drug, circulating IgE can bind to the free, soluble penicillin (hapten recognition), the complex is bound by Fc receptors on mast cells which induces rapid degranulation and release of histamine and other inflammatory mediators that cause an immediate hypersensitivity reaction, occasionally leading to fatal anaphylactic shock. 3-6% of people react to penicillin at least in a skin test, and about 0.004-0.015% develop anaphylactic shock.
what are the two major light chains?
kappa and gamma
in most cases, the light chains are joined to the heavy chains by what?
intermolecular disulfide bonds
the heavy chains of antibodies are composed of how many Ig domains?
5-6
immunoglobulins bind the antigen with which domain?
N-terminal V-domains (7-8 Beta sheets connected by alpha helices)
what are Framework regions (FRs)?
very similar portions of discrete immunoglobulin V domains
There are __ CDRs and ___ FWRs in Ig proteins
3; 4
what are the two heterodimers of TCRs?
aBTCR and the gdTCR, which are always expressed mutually exclusively in two different lineages of T cells, the aBT cells and the gdT cells, respectively. In humans, aBT cells make up >95% of all T cells and represent the major arm of the adaptive cellular immune response. The functions of gdT cells are less well understood. gdTCRs typically recognize antigens that are structurally very different from the aBTCR, in many aspects more similar to immunoglobulins, as some gdTCRs may interact with soluble non-peptidic molecules, as well as with soluble proteins. The aBTCR, with very few exceptions, recognizes only linear, peptide antigens associated with MHC proteins.
immunoglobulins bind to antigens with a wirde range of affinities on the order of what?
10^-7 to 10^-11
Antibodies undergo __________ to increase their binding or form _________ in order to achieve higher avidity of binding.
affinity maturation; multimeric complexes
what are the three levels that lead to diversity of the human antigen receptor repertoire?
combinatorial diversity, junctional diversity, heterodimerization
when the BCR binds the antigen, other B cell surface proteins like the ______ also bind as coreceptors to antigen-complement complexes. While such coreceptor binding does not improve antigen recognition (in contrast to T cells), what does it do?
complement receptors (CD19/21), enhance B cell stimulation
When B cell surface molecules like ______ bind the antigen-antibody complexes simultaneously with the BCR, the result is inhibition rather than activation of the B cell
Fc gamma receptors
What are the immunoglobulin signal trasduction molecules?
Igalpha and Igbeta
how can a single lymphocyte encounter one specific antigen effectively?
adaptive responses initiatied in the secondary lymphoid tissues (helps increase antigen [ ] , spacial organization of the response, and Tcell-Bcell collaboration)
what is it called when one TCR occasionally recognizes two unrelated peptide-MHC complexes?
cross reactivity - could underlie some cases of self-recognition like a foreign peptide MHC mimicking the strucutre of a self peptide-MHC complex, which can lead to autoimmunity
TCRs bind to antigen typically with high or low affinity?
low (106-4 to 10^-6)…but the effectiveness of T cell recognition is not proportional with the strength of binding to its cognate antigen, and TCRs do not undergo affinity maturation under any circumstances. The strengths of the TCR bindign will, however, influence the outcome of T cell activation (depending on the developmental stage of the T cell, relatively strong TCR binding can activate or kill the T cell)
how can very few lymphocytes produce a large enough repsonse?
clonal expansion
what are the 3 signals delivered by APCs to naïve T cells?
- MHC to TCR 2. costimulation (B7 to CD28) 3. cytokines (IL-6, IL-12, TGF-Beta) released from APC to T cell)
what transmits the signal inside the cell to a chain of signal transduction proteins in when the TCR binds the MHC complex?
CD3
what do gammadelta T cell receptors bind?
MHC I-like molecs without associated peptides (T22), or soluble ligands like Igs do
what do iNK TCR bind?
non-peptide, lipid antigen (CD1d)
what are preBCR?
expressed only in early B development (preB) no antigen recognition
preTCR?
expressed only in early T cell development (preT) no antigen recognition
isotypes that function in neutralization?
IgA, IgM, IgG
isotypes that function in opsonization?
IgG1, IgG3
isotypes that funciton in IgE-mediated reactions?
IgE
isotypes that funciton in complement activation?
IgM, IgG1, IgG3
isotypes that function in mucosal and placental transport?
IgA, IgG1, IgG2, IgG4
The isotype of an antibody is det by the ____ region of the heavy chain.
C
4 methods Ig Neutralization?
- Ab blocks penetration of microbe through epith barrier 2. Ab block binding of microbe and infection of cells 3. Ab blocks injection of adjacent cell 4. Ab blocks binding of toxin to cellular receptor
name the isotype: neutralization of microbes and toxins, opsonization of antigens for phagocytosis by macrophages and neutrophils, activation of the classical pathway of compelemnt, Ab-dependent cytotoxicity mediated by NK cells; neonatal immunity: transfer of maternal Ab across placenta and gut, feedback inhibition of B cell activation
IgG
name the isotype: activation of the classical pathway of complement?
IgM
name the isotype: mycosal immunity: secretion of this into lumens of GI and respiratory tracts, neutralization of microbes and toxins
IgA
name the isotype: antibody-dependent cellular cytotoxicity mediated by eosinophils, mast cell degranulation (immediate hypersensitivity reactions)
IgE
low affinity ____ receptors on NK cells permit the identification of the target cell which is then lysed by the NK cell. In contrast to opsonization, the microbe is not phagocytosed, but killed by the cytotoxic compounds released by the NK cell.
FcgammaIIIA
ADCC mediated by eosinophil granulocytes utilizes ____ and ____ and is important against ___ infections.
IgE, FcepsilonRI, worm
IgA and J chain are produced by what? What about the Poly-Ig receptor?
B-cell, epithelium
The mucosal tissues represent the first line of defense against infection and are well endowed with both innate and adaptive protective mechanisms. The major adaptive protection is derived from mucosal and intraepithelial B and T cells and mucosal antibodies of _______ isotypes
IgA (and less so IgG)
Transport of IgG1 and IgG3 across the placenta and neonatal intestinal epithelium into the blood circulation is mediated by a specific neonatal Fc receptor (________) with a structure more similar to MHC class I molecules than to most other Fc receptors. Since newborns do not produce significant amount of antibodies for about 6 month of age they must depend on the adaptive protection provided by their mothers.
FcRn
polio vaccine?
oral attenuated; neutralization of virus by mucosal IgA antibody
tetanus, diptheria vaccine?
toxoids; neutralization of toxin by systemic IgG antibody
Hep A/B vaccines?
recombinant viral envelope proteins; neutralization of virus by systemic IgG abtibody
pneumococcal pneumonia, haemophilus vaccine?
conjugate vaccines composed by bacterial capsular polysaccharide and protein; opsonization and phagocytosis mediated by IgM and IgG antibodies, directly or secondary to complement activation
