- b cells make them in response to antigenic stimulation (help TH2 cells which make cytokines that make B cells better at making antibodies
3 BIG WAYS TO THINK ABOUT WHAT ANTIBODIES DO
1. opsonization - taking a host protein and sticking it on the surface - serves as a ligand for a receptor (rather than having to recognize each unique bacteria) - makes it easier for phagocytes to get ahold of it - has receptors for Fc portion of antibody
2. complement activation - certain proteins that are anti-bacterial
3. neutralization - bind to surface of pathogen and prevent it from attaching to host
- Look at this for a spell
- Antibody production initiates ___ days after initial exposure to antigen, and only if the immune processes _______
- 3-7 days, fail to clear it rapidly
- Antibodies (Ab), also called _____, are ______. Ab are principle mediators of _____, and the production of an appropriate Ab response to infection that is a major contributor to _____. Ab are secreted ____ found in the ____ and on _____ at varying concentrations.
What are the red regions in the picture?
Are both sides identical?
What do they do?
What is the blue region? defined by what?
- immunoglobulins (Ig), antigen-specific products of B cells, immunity, immunity, proteins, plasma, surfaces
- variable regions
- yes, have identical antigen binding pockets
- bind to the antigen (different size sockets)
- constant region, heavy chains (ratchet)
- _____ proteins produced by ___ cells (2 ____ plus 2 ____ chains) - for every given b cell - the antibody they make is ____
- ______ specific
- divalent, two _____
- bifunctional - one side _____, other has _____
- interact with Ag _____
- Different constant regions divide Ig into classes or _____ - list them bitch
- heterodimeric, B, heavy, light, exacly the same
- binding pockets
- binds antigen, chemical properties he'll talk about
- non-covalently (electrostatic forces, hydrogen bonds, Van Der Waals forces, and hydrophobic)
- isotypes (IgD, IgM, IgG (several), IgE, and IgA)
- All Ab have the same basic structure
- _ ______ lights chains ( __ kDa), __ _____ heavy chains (50-80 kDa)
- Subunits are ____ linked
- The ____ subunit determines the IgG class
- Distinct Ab regions are determined by _____
- ___ portion contains the heavy chain constant region
- ____ portion contatins the Ab binding site
- 2 identical, 25, 2 identical, 50-80
- Ig class (isotype)
- Fc (fragment of crystalization - aka constant fragment)
- Fab (fragment of antigen binding)
- Look at this -
what is arrow at top pointing at?
In what ways have antibody molecule been defined by parts?
What does papain do?
- Ag binding site at junction of Vh and Vl light chains
- proteolytic digestion and function
- separates in Fc and Fab region by breaking disulfide bonds
What is the antigen binding pocket formed by? What is it encoded by? What does it undergo to generate Ag binding pockets of varying ______?
Which is the region of the antibody that many cells have receptors for?
Within an individual, every ____ cell will have a slightly different binding pocket?
- variable regions of the Ab H and L chians
- multiple gene segments
- mutation, strength
- The Fc region (back part of the heavy chain)
- The binding pocket interacts with the epitope in a _____ manner. It uses those forces mentioned earlier instead. The binding can be very ____. But it is _____
- Ab bind to the Ab in its ____ form. Becaus all Ab are _____ - they can do what?
- native - multivalent - bind two of the same epitope on a single antigen or two of the same epitopes on two different antigens
What determines the isotypes?
First heavy constant region coding sequence downstream is ____. So when every B cell first differenitates in bone marrow - the first antibody they make is
- Isotypic differences are in ____
- Allotypic differences are in___
- Idiotypic Differences are in ___
- the heavy chain constant region
- IgM, IgM (because its the first part downstream from the section than encodes the variable region)
- heavy chain (affects where antibody ends up, what it can do)
- alleles - doesn't affect function too much
- in the antibody binding site - variable regions are different - bind different epitope
______ - any cell that has differentiated in the bone marrow - now making ____, first one it makes is ___
- _____ cell is a b cell that has been activated to secrete _____. where is it at?
- Where do memory cells go?
- B cell, antibody, IgM
- plasma, Antibody, out in the blood throwing down
- end up in lymphoid tissues in the bone marrow and last a long time
When B cells leave bone marrow what do they look like?
What's the first thing a b cell does upon activation? What antibiody will that be?
When IgM is secreted it is secreted as a _____.
IgA is secreted as a ______.
What protects these from degradation?
State of the ag binding site between IgM pentamer and IgA dimer?
- circle with one line then two - these are antigen binding sites - these antibodies are all IgM
- secrete antibodies, IgM
- The J chain
- Ag specificity is identical
Iga is important for what kind of immunity?
What is used to transport dimeric IgA across epithelial barriers to coat mucosal surfaces?
What type of receptor does IgA bind to to get transported to lumen (from inside to out)?
- the J chain
- poly-lg receptor
- Ig constant regions confer ______ (examples IgG and IgM activate classical pathway for complement.......IgE binds to mast cells and basophils)
Does relative expression of each isotype vary?
- _______ results in only one chromosome rearrangement per cell
What gives your variety of binding pocket?
- functional capacity
- yes - G > M > A in blood, A >> M > G on mucosal surfaces
- allelic exclusion
- the sufflage of genes
Be aware of this table - not sure if i need to study it or not
- which one can you forget about (IgD)
- Isotypes are encoded by a cluster of _____
- What isotypes are made later when B-cell is out in periphery is determined by which _____ it encounters when it is being activated
- heavy chain genes
- Mast cells have receptors for ___
- The heavy chain of ____ is recognized by receptors on phagocytes
- ___ is secreted across epithelial layers to provide protection at mucosal surfaces
- What antibody deficiency would lead to alot of respiratory infections? Why?
- IgA, mucous
What does hinge region do on antibody?
Know the picture
- gives it some flexibility upon binding
- Antibodies are __ - functional
- Each B cell makes a unique _____, generated via rearrangment and mutation of the germline ___.
- receptor, DNA
get a feel for this table... its in you photos on ipad
THIS IS WHERE LECUTRE & SHOULD HAVE STARTED
How do B cells develop receptors (antibodies) that can bind to almost any epitope?
The recion of the antibody gene that binds the epitope is ______________, thus creating different exons fort eh anitbody chains within each B cell
Where does this occur...what is affected ?
- fake you out
- generated by a semi-random rearrangement of gene segments
- the heavy and light chain variable regions
(B cell development)
- B cells start out in the _____ and ____ by rearranging their _______ to create the exon encoding the _____ (both the heavy and light undergo this process)
- The only isotype generated at this stage is ___ (and a little ___)
_______ - if an antibody gets rearranged in the bone marrow it gets killed
- bone marrow, fetal liver, chromosomal DNA, antigen binding pocket
- IgM, IgD
- look at this
(Antibodies - DNA Rearrangement)
- The heavy and light chain genes consist of large numbers of _____ genes, ______, and ______ regions.
- The variable region genes are constructed by joining ____________ to form a continuos piece of DNA
- _______ must occur to form a joined gene
- What regions to light chains lack?
- Rearrangement is a random event which occurs only on ____ chromosome for each light or heavy genes (called _____)
- The constant region is encoded by separate ____ and is joint to the variable region exon by _____ of the primary ____ transcript.
- ______ can occur following VDJ region recombinations
2 * 10^6 possible H + L combos
- variable (V) domain, joining (J), (+-) diveristy (D)
- one of the gene segments from each region (one V + one D + one J segment)
- Somatic rearrangment
- one, allelic exclusion
- exons, splicing, RNA
- Isotype switching
- The immune system has the capacity to recognize approximately 10^10 different _______. Although each B cell produces antibodies of a ____ specificity, other B cells synthesize Ab to recognize other ______. Hence the pool of B cells within and individual provides universal recogntiion.
What are the five things that achieve antibody diversity (for more info on each refer to picture in ipad)
- antigenic epitopes
1. Multiple germline gene exons
2. H and L chain combinations
3. Imprecise joining of segments
4. Random intsertion of bases
5. Somatic hypermutation
(first 4 happen during b cell differentiation in bone marrow - fifth occurs only after a b cell encounters its specific antigen)
READ MORE ABOUT THESE IN NOTES
(Early B cell Development)
- B cells begin development in the ____, where stromal cells secrete ______.
- As a pre-B develops, the antibody genes begin to ______ (_____ first, then ____)
What cells survive and leave the bone marrow?
What drives differentiation of lymphocytes (especially B cells)?
- bone marrow, B cell growth factors
- rearrange, heavy-chain, light chain
- those cells that successfully rearrange both heavy and light chain genes