3. Antigens and Antigen Receptors Flashcards
Paratopes
antigen binding sites on antigen receptors
Epitopes/antigenic determinant
the part of the antigen that binds to paratopes
immunogen
any molecule or group of molecules
that induce an immune response
hapten
Small molecule that can act as an
epitope but not elicit an immune response
Non microbe derived antigens
pollen, food and dust or ‘self’ antigens
how do antigens enter the body?
– breaks in the skin and mucous membranes,
– direct injection, as with a bite or needle or through
– organ transplants and skin grafts
– M cells in the mucosal surfaces
complex antigens
have many different antigenic determinants - e.g. viruses
Adjuvants
enhance the immune response to an antigen,
making it more immunogenic
what do adjuvants increase?
• persistence (‘depot’)
• effective size (for uptake by APCs)
• activation of dendritic cells, macrophages →
inflammatory cytokine production
examples of adjuvants
• Complete Freund’s adjuvant (oil, water, dead/lysed
mycobacteria)
• Alum (aluminium potassium sulphate)
what do T cells bind to?
linear arrays of
approximately 9 amino acids - antigens that have been broken down into peptides and presented on cells
immunoglobulins
proteins that recognize and bind to a particular antigen with very high specificity
how do BCR and B cell antibodies differ structurally?
BCR has a short cytosolic tail
Fab region
contains the variable
antigen binding site
Fc region
rest of the molecule has a relatively constant structure
how many variable regions are there in the antigen binding site?
2 - heavy and light
what type of chains are light constant regions?
kappa or lamda
what type of chains are heavy constant regions?
mu, gamma, alpha, delta and epsilon
CDRs
complementarity-determining regions - immunoglobulin-like domains that
contain 3 hypervariable loops between
the strands of the β-pleated sheets
IgM
Found on the surface of naïve B cells
IgA, IgE and IgG
Found on the surface of B cells that have been
activated and have undergone “class-switching”
IgD
Found on all B cells
antibody monomers
G, D and E
antibody dimer
A
antibody pentamer
M
B cell antigen receptor (BCR) complex
Comprises membrane-bound Ig (mIg)
AND 2 Igα and 2 Igβ chains (CD79a
and CD79b)
ITAMs
Immunoreceptor Tyrosine kinase
Activatory Motif - important for signal transduction, in cytoplasmic chains
ITAM signalling leads to…
development of either plasma or
memory cells
where are Immunoglobulin-antigen interactions located?
at the furthest extreme
of the heavy (VH) and light chains
(VL)
why is a high affinity
antibody is more protective than a low
affinity antibody
it will bind
antigens at lower
concentrations
avidity
the total strength of binding of the Fab
regions of the population of antibodies raised against an antigen, and
involves the reaction with all antigenic determinants
immunoglobulin fold
a protein domain of Anti-parallel β-pleated strands and includes a disulfide bridge
what are the Two types of TCR
αβ and γδ
how many antigen binding sites do TCRs have?
one
how does TCR signal?
it can’t itself - instead CD3 does
CD3 structure
consists of 6 polypeptides; ζζ, γε and εδ dimers
MHC class I recognised by…
CD8 - cytotoxic
MHC class II recognised by…
CD4 - helper
classical T cell activation steps
- variable regions of TCR interact with peptide in MHC
- epitope must be complementary to paratope
- CD4/8 joins the complex
- kinases and ITAMs stimulate activation
superantigens
proteins that bypass normal antigen recognition. not processed by antigen presenting cells
where do superantigens bind to in order to bypass normal antigen recognition?
– non-variable sequences of TCR variable regions
– non-polymorphic sequences of MHCII α-chain
where are γδ T cells found?
mostly in epithelial rich
tissues e.g. foetus, mucosa
how do γδ T cells differ from αβ T cells?
less diverse. recognise antigen presented in CD1 rather than MHC. recognise lipids, pathogens (such as M. tuberculosis) and pathogenic toxins
presentation
how complex antigens/proteins are broken down
into peptides and loaded into molecules
MHC class 1 recognises…
endogenous antigens
MHC 2 recognises…
exogenous antigens
MHC 1 structure
single polypeptide chain, bound to β2-microglobulin. a1 and a2 domains consist of 4 b strands and an a helix. These form a groove or cleft which is the Ag-binding site
where is MHC 1 found?
on all nucleated cells & platelets
where is MHC 2 found?
On professional Antigen presenting cells - Dendritic cells Macrophages B cells
MHC 2 structure
two chains a and b
dendritic cells location
Skin
GI and respiratory tracts
Parenchyma
capture and presentation of protein antigens by dendritic cells
- antigen is processed
- dendritic cells become migratory - detach and enter lymphatics
- enter paracortex area of lymph nodes
- then become positioned on the fibroblastic reticular cell network
- scanned by naive CD4/8 T cells
processing endogenous antigens
processed by proteasome and imported into ER. loaded into MHC 1 and transported to cell membrane
processing exogenous antigens
engulfed into endocytic vesicles and degraded. loaded into MHC 2 and transported to cell membrane
how are proteins marked for degradation?
ubiquitination
TAP
transporter associated with antigen processing
immunoglobulin genes contain…
– V = Variable Segments
– D = Diversity Segments
– J = Joining Segments
positive selection of b cell development
cells that cannot make functional heavy or light chains die by apoptosis
negative selection of b cell development
cells that bind to self
molecules whilst arranging their BCRs die by apoptosis
when does thymocyte expression of TCR begin?
after rearrangement
of the DVJ segments genes encoding α and β chains
HLA
Human leukocyte antigens - a single stretch found on
Chromosome 6 in humans that contains genes for the MHC and other immune-related
genes
MHC 1 HLA genes
A, B and C
MHC 2 HLA genes
DP, DQ and DR
advantage of diverse MHCs
provides resilience in a population to emerging pathogens
disadvantage of diverse MHCs
makes tissue typing in organ transplantation essential to avoid rejection
of the organ as “non-self”
polyclonal response
many
clones of B and T cells will expand as they recognise
the different antigens and/or different epitopes within
them
