Antibodies Flashcards
(34 cards)
Naive B cells
cells that have not met antigen, circulate from blood into peripheral lymphoid tissues (main site on antigen encounter)
tell me about the structure of lymph nodes
cortex and inner medula
- Cortex has an outer section of B cells organised into follicles
- a paracortical area of T cells and dendritic cells
- Germinal Centres of B cell proliferation form during an immune response
- Medulla consists of macrophages and antibody secreting B cells (Plasma cells)
- Antigen (in DC) enter through afferent lymphatics.
red pulp of the spleen
site of RBC destruction
white pulp of the spleen
White pulp is lymphoid
pathway through the spleen
- Blood carrying lymphocytes
and antigen enter from a trabecular artery into a central arteriole - they pass into a marginal sinus and exit through a trabecular vein
marginal sinus
surrounded by lymphocytes, and within it is the periarteriolar sheath (PALS), made up of T cells
B cell follicles and a B cell corona also form. Important - antigen enters from blood rather than lymph.
key features of adaptive immune response
antigen specificity, and memory the secondary (memory) response is faster, can produce more antibody, and does not prevent you from making a response to another antigen (multiple antigens -vaccination)
Antibodies can be expressed as
membrane bound (B cell receptor - BCR) or secreted forms. B cells express a single Ab specificity only
what are the functions of Ab cells
- firstly to bind the pathogen that elicited its production
- secondly to recruit other cells and molecules that will lead to clearance or destruction of the pathogen
Ab structure
- made of four polypeptide chains, two identical heavy (H) chains and two identical light chains (L)
- The H chains are disulfide bonded to each other, and each H chain is also disulfide bonded to a L chain
two types of L chain
lamba (!) and kappa (“). Any individual Ab has either ! or “, never a mixture of each. In human the ratio is 2:1 in favour of “.
Two identical H and L chains results in two identical binding sites.
Crystal structure of antibody shows a Y shape consisting of three globular domains
VL - variable light, CL - constant light, VH - variable heavy, CH1 - constant heavy 1
Proteolytic digestion reveals
functional domains of Ab
The binding site for antigen
is contained where
in the Fab region whilst The Fc region performs many of the functions of Ab, interacting with receptors etc
what can be used to label cells
Fab and F(ab)2 fragments
are very us in the lab without inducing the effects
of the Fc region, or in the case of Fab fragments, inducing receptor triggering or internalisation by crosslinking
Hypervariability in V domains
- Three hypervariable loops determine antigen specificity by forming a surface complimentary to the antigen.
- Final specificity is determined by a combination of loops from H and L chains, and not either alone.
Antigen binding to Ab
Antigens can bind in pockets or grooves, or on extended surfaces
antibody repertoire
The total number of antibody specificities available in an individual
humans its = 10’11
Germline Theory
suggested that a separate gene existed for each Ab. Not really the case.
Somatic Diversification theory
proposed that repertoire is generated from a limited number of V region genes that undergo alteration. Essentially correct.
Chromosomal Rearrangement
The sequence of a V region is generated by the somatic recombination of separate gene segments
Junctional Diversity
N-nucleotides, (non template-encoded) are added by terminal deoxynulceotidyl transferase (TdT).
After upto 20 nucleotides are added, pairing is attempted, followed by trimming off nonmatching bases, filling gaps and ligation to complete.
• Ab diversity is created by
- 1 -rearranging multiple gene segments
- 2 - junctional diversity
- 3 - different combinations of H and L chains
- All the above happen during B cell development, long before it ever sees antigen
Somatic Hypermutation
occurs after B cells have become antigen activated in the lymph node.
