Antibody, lymphocytes and the Generation of Diversity Flashcards
Definition of adaptive immunity
Not as fast as innate, more specific and has memory. Depends on cells that are individual, recognize their own unique antigenic shapes
Definition of heterodimer
2 different chains
Definition of memory cells
More abundant form of a cell with a specific receptor. Can result in an even more rapid response when antigen encountered again
Definition of gene rearrangement
VDJ somatic recombination, results in a unique amino acid sequence in the antigen binding region
Definition of junctional diversity
DNA sequence variants introduced by improper joining of gene segments during VDJ recombination
Definition of agglutinization
Dumping of particles with antibodies and the complementary antigen. Makes it easier for pathogens to be phagocytosed
Definition of affinity maturation
Somatic hypermutation and selection of high affinity variants. Results in an antibody that binds better to antigen than original
Definition of monoclonal antibodies
Antibodies made by identical immune cells, clones of a unique parent cell with monovalent affinity
Definition of polyclonal antibodies
Antibodies secreted by different B cell lineages. React against a different specific antigen
Definition of chimeric antibodies
Made by fusing antigen binding region from 1 species with the constant domain from another species
Definition of humanization
Only parts of the variable region that contact antigen are transgenic
Compare the
- time
- memory of innate and adaptive immunity
Innate
- minutes-hours
- no memory
Adaptive
- primary response 12 days
- secondary response 5-7 days
- increased frequency of specific cells
Describe the
- receptors
- gene segments
- no of binding sites found on T and B cells
T cells
- ab heterodimer
- VCJ, VDCJ
- 1 binding site
B cells
- lamda or kappa light chain
- VJ, VDJ
- 2 binding site
Describe the process used to create diversity in B cell receptors
Combinatorial diversity- HLA on chromosome 14
Heavy chain
-VDJ
Light chain
-VJ, intervening DNA removed as a loop
Junctional diversity
-imprecise segment joining, nucleotides added/lost
Location of gene rearrangement
- T cells
- B cells
PRIMARY LYMPHOID ORGANS
T cells
-thymus
B cells
-bone marrow
What happens when cells are activated via their receptors
- T cells
- B cells
T cells
-differentiate to mature Th cells/effector CD8
B cells
-Matures in to plasma cell, produces complementary AB
How do ABs bind
Bind via
- shape
- electrostatic interactions
- hydrostatic interactions
Describe the
- shape
- function
- location of IgA (1,2)
Shape
- monomer in serum
- dimer on mucosal surfaces, attached via J chain
Function
- agglutination
- neutralisation
Function
- adheres to basolateral mucosal surface via secretory component
- IgA can then be transported into the gut
Describe the
- shape
- function of IgD
Shape
-monomer
Function
- v little in serum, expressed with IgM with immature B cells
- have the same specificity
Describe the
- shape
- function of IgE
Shape
-many monomers bind to mast cells via Fc
Function
-When allergen crosslinks with IgE => histamine release
Describe the
- shape
- function of IgG (1,2,3,4)
Shape
-monomer
Function
- opsonisation, activation of NK cells via Fc receptor
- most abundant in serum (vaccine response)
Describe the
- shape
- function of IgM
Shape
-pentameric, 10 binding sites => high avidity
Function
- first AB made in immune response
- lattice formation in agglutination, complement fixer
Describe the steps involved in affinity maturation
-what cells are involved in affinity maturation
ONLY IN B CELLS => IMPROVE ANTIGEN SPECIFICITY
- Lymphocytes circulate blood and lymph
- Activated B cell enters germinal center of secondary lymphoid organs
- Rapid division and somatic hypermutation of variable region
- High affinity variants selected by Th=> results in AB that binds better to antigen than original
- Constant region can also class switch
What types of B cells can be generated from the germinal center
What are their functions
B memory cells
- migrate to spleen
- reactivated in subsequent contact with same antigen
Plasma cells
- IgA => GI
- IgG => bone marrow
- secrete high affinity AB
Describe how IgG and IgM nos differ in a primary and secondary response
Primary response
- B, T cells interact with antigen => affinity maturation in GC
- Plasma cells => increased titre
- IgM first generated, IgG conversion starts
- Short lived plateu, AB con falls
Secondary response
- IgG rises faster, peaks sooner
- IgM response doesnt change
- higher overall titre due to increased affinity
What are monoclonal antibodies
How do they differ from polyclonal antibodies
Normal B cell populations = polyclonal
Memory clones different due to somatic hypermutation
Monoclonal antibodies are all the same, come from the same plasma cell
Describe how monoclonal AB are made
1 B cell with 1 specificity expanded as a clone
Mature into plasma cells, release same AB
What are the 3 types of monoclonal AB
- how do they differ from each other
- what drug endings do they have
Chimeric
- mouse variable
- human constant
- ximab
Humanised
- some mouse variable
- human constant
- zumab
Human
- human variable and constant
- umab
What are the functions of the antigens on RBCs
- ABO
- Rh
- Kell
- Cromer
ABO
-a mystery
Rh
-NH4 transporter, CO2, NH2 diffusion
Kell
-endothelin NH2 converting enzyme
Cromer
-complement inhibition
Describe how Rh -ve mothers can cause problems during a Rh +ve pregnancy
How is this resolved
-ve mother produces IgG to Rh after Rh exposure from 1st pregnancy
IgG crosses placenta in 2nd Rh +ve pregnancy => hemolytic disease in fetus
Plasmapheresis removes IgG from baby
