Intro to B cells, T cells. and Abs Flashcards
What is a B cell Ag?
A substance that binds to Ab, can be any organic molecule such as protein, carbohydrate or DNA
What is an epitope?
portion of Ag recognized by an Ab, mostly discontinous (can be linear or 3D)
What is a polyclonal antisera?
A collection of different Ab.s from serum that recognizes different epitopes of the same antigen
What is a mAb?
Ab dervied from a single B cell clone; has the same specificity/epitope; used as tools in research and therapies to treat disease
What are the different chains that compose an Ab, and how are these chains held together?
- 2 identical heavy and light chains
- held together by interchain and intrachain disulphide bonds
How many light and heavy chain genes do humans and mice have, and how many alleles are there for the light and heavy chain genes?
2 light chain genes:
- kappa and lamda (4 alleles)
1 heavy chain gene (2 alleles)
What are the five isotypes of heavy chain genes?
IgM, IgD, IgG, IgE, IgA
What is the function of the variable region of the light and heavy chain?
binds Ag
What is the function of the constant region of the light and heavy chain?
important for the structure of Ab, and C-term constant regions of heavy chain have effector functions
Each Vh/Vl and Ch/Cl region on an Ab form a conserved structure, what is this called?
immunoglobulin (Ig) domain
What are the functions of the hinge regions and carbohydrates on Ab.s?
Hinge:
- found on some isotypes
- gives flexibility
Carbohydrate:
- have effector functions
- e.g. attract complement
What does the Fab and Fc regions of Ab.s stand for and what do they encompass?
Fab:
- fragment Ag-binding
- Vh and Vl
- contains Ig domain
Fc:
- fragment crystallized
- carbohydrates (CHO)
- heavy constant region
Where are Ig domains found, besides Ab.s?
- TCR a and b chains
- CD4
- CD8
- MHC-I
- MHC-II
What are some characteristics of the Ig domain?
- 110 a.a. in size
- each domain consists of two b sheets that form a B sandwich/barrel structure
- B sandwhich is held together by a disulphide bond and hydrophobic interactions between the sheets
- contain complementary determining regions (CDRs)
What are the CDRs on Ab.s and what is their function?
3 loops in the VL and VH that connects beta strands are highly variable between Ab.s of different specificities - form the Ag binding site
What are the CDRs of the TCR and what is their function?
CDRs of the alpha and beta chains of the TCR form the Ag binding site
How are the BCR and TCR modular receptors?
contain Ag binding sites (BCR = Ig; TCR = alpha (gamma) and beta (delta)) and signaling subunits (BCR = Igalpha and Igbeta; TCR = CD3)
What processes is BCR signaling critical for?
- B cell development
- mature and memory B cell activation
- survival of mature naive B cells
What are the BCR signaling subunits and what are some of their characterisitcs?
subunits = Igalpha and Igbeta
characteristics:
- nonconvalently coupled to the light and heavy chains
- contain ITAMs in their cytoplasmic regions
What are the Ag-binding subunits on a TCR, how are these similar to BCR subunits, and what do they bind?
subunits = alpha (gamma) (similar to Ab light chain), beta (delta) (similar to Ab heavy chain)
bind specific MHC + peptide combinations
What are the signaling subunits of a TCR and what is an important characteristic of them?
subunits = collectively called CD3
important characteristic = contain ITAMs
What is TCR singling critical for?
- T cell development
- activation of mature/memory T cells
- T effector cell function
- survival of mature, naive T cells
What are the functions performed by Ab.s, and call all these functions be performed by Ab.’s with different isotypes?
- neutralization -> inactivates pathogens and toxins
- agglutination -> similar to neutralization -> pathogens stick together and cannot enter cells
- opsonization -> make a pathgoen tastey -> marks pathogen for phagocytoksis
- complement activation -> opsonization of Ag.s, and formation of MAC -> lysis of pathogen
- ADCC -> NK cells kill tumour and unhealthy cells via inducing apoptosis
- degranulation -> trigger mast cells, eonsinophils to degranulate (used for bigger pathogens)
not all isotypes perfom all these functions
What is an Ab isotype?
Ab.’s with different CH regions
How do Ab isotypes differ from one another?
with respect to sequence and number of Ig domains (4-5 domains/heavy chain). Different isotype constant (Fc) regions perform different functions
Which Ab isotypes are secreted as monomers, dimers or pentamers? How are the polymers (dimers and pentamers held together)
monomers: IgD, IgG and IgE
dimer: IgA
pentamer: IgM
dimers and pentamers held together via a J chain
Which Ab isotype is the most versitile?
IgM
Which Ab isotypes highly activate the complement pathway?
IgG and IgM
Which Ab isotypes crosses the placenta well?
IgG
Which Ab isotypes are present on the surface of mature B cells?
IgM and IgD
Which Ab isotypes bind to FcR of phagocytes well?
IgG (mostly), some IgM and IgA
Which Ab isotypes mediate mucosal transport via poly-Ig R well?
IgA
Which Ab isotype induces mast cell and/or basophil degranulation the best?
IgE and IgD
What were the two puzzling questions to early immunologists?
- how can Ab.s be generated against almost any organic molecule?
- how does the body produce the appropriate Ab for an infection?
What is the clonal selection theory?
a theoretical model to explain how pathogens select B cells to secrete Abs (also holds true for hot T cells are selected by Ag)
What are the four tenets of clonal selection theory?
- each B cell expresses on its cell surface and Ab of one specificity
- Ags select specific B cells for activaiton
- effector B cells (plasma and memory) have the same Ag. specificity as the original B cell that was selected by Ag
- B cells that recognize self Ags are removed from the repertoire during development
