IAI - Antibody, lymphocytes, and generation of diversity Flashcards
describe adaptive immunity
- not as fast at innate
- specific
- has memory
what does adaptive immunity require
- Adaptive immunity requires lymphocytes.
- Both T and B cells.
Outline the structure of a T cell.
- heterodimer
- one binding site for antigen (blue)
- made of an alpha chain and beta chain
Outline the structure of a B cell.
- it’s an antibody moelcule
- two antigen binding sites
- two identical heavy chains (inner chains)
- two identical light chains (outer chains)
what does adaptive immunity depend on?
- Depends on cells that are individual and recognise their own unique antigen shapes.
- Also constant migration of lymphocytes with diverse receptors through blood and lymphoid tissues increases the probability that they will encounter specific antigens.
memory in adaptive immunity allows for
- higher frequency of specific cells
- respond more quickly
(NOTE - SAME PRINCIPLE FOR B AND T CELLS)
Compare the duration of innate and adaptive immunity.
Innate immunity:
- Minutes to hours
Adaptive immunity:
- First exposure (primary response) - 12 days
- Booster (secondary response) - 5-7 days
Which part of the lymphocyte is variable and which part is constant?
The tip of the cell receptor is variable and the rest of the receptor is constant.
What do we depend on to generate diversity in lymphocytes?
gene rearrangement
The tip of the variable region of the HEAVY CHAIN is composed of three parts, what are they?
- Variable
- Diversity
- Joining
The tip of the variable region of the LIGHT CHAIN is composed of two parts, what are they?
- variable
- joining
What is the number of possibilities for a rearranged combination of V, D and J in heavy chain, and in light chain, and then the combinatorial diversity of light and heavy chain together?
- Variable: 48 options
- Diversity: 27 options
- Joining: 6 options
48 x 27 x 6 = 7776 different combinations of heavy chain
340 combinations of light chain
So, for one heavy and light chain together there would be
7776 x 340 =
2,643,840 variants
= Combinatorial diversity
How is further diversity created in gene rearrangment?
- Further diversity is created by JUNCTIONAL DIVERSITY the mechanism that joins the segments together.
- This is very imprecise.
- Nucleotides are added and removed from junctions during rearrangement.
Where does B cell development occur?
bone marrow
Where does T cell development occur?
made in bone marrow, matures in thymus
What happens when a cytotoxic T cell is activated by its T cell receptor?
It differentiates to secrete cytotoxic granules.
What happens when a helper T cell is activated by its T cell receptor?
It differentiates to produces different sets of cytokines.
in the structure of an antibody, what 2 chains are they made of
2 light chains
2 heavy chains
in the structure of an antibody what are the light and heavy chains joined by?
disulfide bonds
the variable regions in the structure of an antibody determine … and are called … or ….
the variable regions in the structure of an antibody determine SPECIFICITY and are called KAPPA or LAMBDA
the constant region of the heavy chain determines ….
the constant region of the heavy chain determines FUNCTION
What gives an antibody its specificity?
Variable regions determine specificity.
- What gives an antibody its function?
The constant region.
What are IgM, IgD, IgG, IgA and IgE?
IgM, IgD, IgG, IgA and IgE are refered to as classes or isotypes defined by the constant regions of their heavy chains.
Remember: GAMED
what is the term Fc used to describe in antibodies?
- The Fc is the term often used for the paired constant region segments.
- Some cells, such as macrophages have Fc receptors and these are the receptors for the Fc regions of antibodies.
what are the 4 functions of antibodies
Neutralise toxins and viruses by binding to them and
blocking their interaction with other cells
Opsonise pathogens by binding to them to promote
phagocytosis and killing activity by other cells by
recognition of Fc receptors
Activate the complement cascade which helps kill
pathogens
Agglutinates particles (pathogen debris, viruses etc)
how does an antibody bind to an antigen?
Antibody binds antigen through the tips of the variable regions.
Direct physical binding can be via shape (lock and key), or electrostatic attractions, opposite charge attraction, hydrostatic attraction
describe the main function of the igG isotype
Main serum antibody
what is igG good at?
opsonisation
which igG is the most abundant
igG1
describe the main function of the igA isotype
can be found in serum as a monomer
what is the structure of igA
dimer = 2 monomers joined by a joining J chain
dimeric igA regulates gut bacteria by?
- IgA as a dimer has four binding sites. Therefore it can agglutinate bacteria and neutralise them that way.
- Also the secretory component parts of the secreted IgA combine very well to mucus, so they can retain antigens on the mucus surface due to charge CHO rich SC
describe the igM isotype?
First antibody made in immune responses.
whats the structure of the igM antibody
- Pentameric
- The pentamer has 10 binding sites and therefore a high AVIDITY - This allows for agglutination.
igE works by association with …
mast cells
describe the process of affinity maturation
What two populations of cells leave the germinal centre?
memory B cells and plasma cells
Describe the primary vs secondary antibody responses.
- lag phase = Bcells and Tcells intercating whlst GC formation is starting
- IgM made first then class switch to IgG and plateus and declines
- secondary: quicker response and higher peak as precursor frequency of specific cells is higher.
- higher titre due to higher affinity
what are monoclonal antibodies
Monoclonal antibodies are powerful laboratory reagents used to treat diseases from autoimmune
diseases such as rheumatoid arthritis, to inflammatory diseases such as
Crohn’s disease, to cancer.
What antibodies end in -ximab?
CHIMERIC antibodies ending –ximab
ie Rituximab - is effective against B cell lymphomas but also some autoimmune diseases including rheumatoid arthritis
What antibodies end in -zumab?
Humanised antibodies have the ending –zumab
ie Omalizumab - is specific for IgE and can be used to treat moderate to severe allergic asthma.
What antibodies end in -umab?
Human monoclonal antibodies have the ending
–umab
An example is antibody adalimumab - is specific for TNFa and is used to treat inflammatory diseases.
what is rhesus disease
haemolytic disease of newborn
describe what happens to a pregnant woman who has the Rh antigen, and the difference between her first and second pregnancy
in the first pregnancy, if both the mother and the baby have the Rh antigen, everything typically goes smoothly. But in subsequent pregnancies, if the mother is Rh-negative and her baby is Rh-positive, her immune system might see the baby’s Rh antigen as a threat and produce antibodies against it, which can cause problems for the baby.
- Cross placental transfer of IgG, causes target of rhesus antigen from mother to fetus causing red blood cell lysis in the fetus and haemolytic disease of the newborn.
- This is resolved by plasmapheresis - the IgG antibodies are removed from the system of the baby, and the baby is then able to create its own red blood cells and is restored to health.
try keats quiz on lymphocyte receptors, B cells, and antibodies
https://keats.kcl.ac.uk/mod/lesson/view.php?id=7651851
what blood type is a universal recipient?
AB
What blood type is a universal donor?
O
The antibody isotypes that can fix complement most efficiently are
The antibody isotypes that can fix complement most efficiently are IgG and IgM. IgA does not fix complement.
