6 - Antigens and Antibody Structure - Partridge Flashcards
Draw a diagram to highlight the initial phases in response to infection
INNATE
INDUCED INNATE
ADAPTIVE
311 - 6 word
Draw a diagram to highlight the OVERALL activation of the adaptive immunity in the draining lymph node
311 - 6 word
Describe the organisation of the lymphoid tissue
Primary lymphoid tissue; lymphocytes reach maturity (B - bone marrow; T - thymus). Antigen INDEPENDENT differentiation -> naive t/B cells
Secondary lymphoid tissue; lymphocytes acquire their specific receptors. antigen DEPENDENT differentiation. eg in lymph nodes, spleen
Antigens are recognised by ____ and ____ receptors on T/B lymphocytes
specific
diverse
What occurs when appropriate receptors on B cells bind to antigen?
undergo clonal selection. B cells w/ correct receptor are stimulated to divide into plasma cells when bind to complementary antigen (which reach a point where they cannot divide further). plasma cells = Ab factories. some B cells retain their antigen receptor and persist as memory cells.
What happens to lymphocytes that recognise self molecules?
detected early in development and degraded
Do T cells undergo clonal selection?
yes, undergo clonal selection in response to antigen
What are the 2 forms that Abs exist as?
- antigen recognition; integral membrane protein bound to B lymphocytes
- antigen elimination; soluble proteins secreted by plasma cells
How does the structure of the antigen relate to its 2 functions in antigen recognition and elimination?
Fab arm; antigen recognition. specific sequences that recognise certain antigens, high sequence variability.
Fc region; antigen elimination. binds to Fc receptors on phagocytes, NK cells and complement to aid clearance of pathogen
Draw the four chain structure of the IgG Ab
311 - 6 WORD
Give the structure of IgG in terms of how many L and H chains there are and give the mw of these chains.
L2H2
L chain = 25kDa
H chain = 50kDa
How can Abs be split up?
reducing followed by addition of an alkylating agent to stop the reformation of the disulfide bridges. in fact, more complicated than this because non covalent interactions also exist
Draw a diagram to show the differential cleavage by papain and pepsin and the fragments that are created. Which one of the Fab fragments will more likely bind to antigen and why?
F(ab)2 more likely to bind. divalent therefore stronger interactions
311 - 6 word
List the 5 main immunoglobulin classes and their functions
IgG - important in secondary responses. main class in serum and tissues
IgM - important in primary responses
IgA - secretions & secretions. protects mucosal surfaces
IgD -?
IgE - present in low amounts, parasites/allergy
Name the 2 light chain types and state whether they are limited to one class.
k and lambda they are not class restricted eg IgGk or IgG(lambda). however Abs of the same type have the SAME light chain
Protein sequencing on which proteins gave more information about Ab structure etc? Why was this protein used?
on myeloma proteins
myeloma = cancer cell in which B cells differentiates and divides uncontrollably therefore producing a large number of Abs. in blood we get large number of homogenous Abs.
Describe the V region of Abs
variable region; differ between Abs of different specificities
Describe the C region of Abs
same for a Abs of a given H chain class or L chain type
Draw the structure of an Ab showing the different V/C regions
311 - 6
Describe 1 homologous domain of an Ab ie anybonds, how many aa’s?
around 110 amino acids, intrachain S-S, folds into compact globular domain known as the immunoglobulin fold
What do all members of the immunoglobulin gene superfamily contain and what type of receptors are they predominantly?
membrane-bound receptors. unlikely to be soluble proteins like Abs. all contain an immunoglobulin fold
Why do some members of the Ig gene superfamily have v similar structures?
gene duplication events of Ig gene leading to a v similar folding pattern
Why can’t we use x ray crystallography to solve the structure of the Ab as one and not as separate parts?
because the hinge region flexibility. means that many conformations will be seen.
What is the hinge region of an Ab made up of?
extended proline chain
Describe the structure of the L-chain C and V regions.
C region;
made up of 7 B strands, intrachain S-S
V region; made up of 9 B strands, intrachain S-S (more complicated region therefore more domain)
how many members of the Ig gene superfamily are there in humans and what are they invovled in?
around 765 members
involved in binding, recognition and adhesion
Draw the looped/B strand structure of the antigen combining site of the V region.
311 - 6
give the name of the 2 main regions within the antigen combining site
framework region
hypervariable region
What is the HVR also known as?
complementarity deterring region
What are the type of interactions between the Ab and antigen?
non covalent interactions eg H bonds, electrostatic interactions, hydrophobic interactions, VDWs
Describe the binding of the antigen combining site and antigen
individually weak interactions but if many interactions form at the same time then then become high affinity and specific. all relies on complementary residues between the antigen and ACS
Overall, name the 3 results that were obtained through studying Ab structure of myeloma proteins.
1) Abs contain V and C regions
2) made up of homologous globular domains
3) the V region is made up of 3 hypervariable regions