Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
32 Cards in this Set
- Front
- Back
|
Types of antibodies? 2 wide classes.
|
IgM- membrane bound antibody
Secreted antibodies |
|
|
What are ARMS?
|
ANTIGEN RECOGNITION MOLECULES (ARMS)
B and T Lymphocytes recognize antigen by using antigen-specific receptors on their surfaces B cells: B cell receptors (BCRs) or Antibody T cells: T cell receptors (TCRs) |
|
|
Function of the constant region on BCR and TCRs?
How does it work? |
-To tell the cell's nucleus that antigen has bound to the receptor.
-BCRs and TCRs use associated invariant molecules to talk to the nucleus. |
|
|
What are the invariant molecules associated with BCRs and TCRs and what do they do? 3
|
-BCRs are associated with Ig alpha or Igß.
-T cell receptors are associated with the CD3 complex *These molecules communicate w/ the nucleus when antigen is bound. |
|
|
Describe how antibodies work:
-what do they recognize? -what functions do they serve in? |
-Antibodies recognize conformational epitopes of native macromolecules and linear epitopes.
-The secretion of antibodies in the extracellular spaces of the body, is the main effector function of B cells in adaptive immunity. -There are several classes of antibodies but all have a common design. |
|
|
Briefly describe structure of antibodies:
|
-2 light chains
-2 heavy chains -Fc region 'tail' binds phagocytes/complement PROs -variable regions for each chain -antigen binding sites are EXTREMELY variable |
|
|
Functional ∆ b/t membrane IgM and secreted IgG:
|
-IgM initiates the humoral response.
-IgG is an effector of humoral response. |
|
|
If the basic structure of all immunoglobulins is the same, how do the receptors of different B cells recognize different antigenic structures?
|
-Antibodies have a modular design (VDJ recombination)
-“Mix-and-match” production technique in bone marrow results in a B cell repertoire that can respond to almost any antigen. -This process generates diversity in the variable domains of the heavy (H) and light (L) chains, which are also the antigen-binding sites. |
|
|
Complementarity-Determining Regions:
|
-They "complement" the antigen that's going to be recognized on the antigen-binding site of the antibody.
-Regions on antibodies that change constantly-- "hypervariable" -There are three of them--CDR 1, 2, and 3. |
|
|
Describe changes that actually occur in the constant domain:
|
-Minor differences in the C domains of H and L chains give rise to constant region classes or isotypes.
-These determine which if the 5 antibody classes it is. |
|
|
types of light chains: 2
types of heavy chains: |
-kappa or lambda
-theta, gamma, alpha, delta, epsilon [one for each class of antibody] |
|
|
What structural characteristic determines the class of antibody?
|
-The Fc region of the heavy chain.
|
|
|
Types of antibodies:
|
IgA (secreted; has J chain connecting two parts)
IgM (membrane bound; pentamer) IgD IgE IgG |
|
|
Describe IgG:
heavy chain type? subclasses? 4 special features/functions? 4 |
-Gamma (γ) heavy chain
-4 subclasses (IgG1, IgG2a, IgG2b, IgG3, IgG4) -Most versatile Ig capable of multiple functions. Role is essential in humoral immunity *Predominant isotype in the blood (75%) *Crosses placenta -Acts as opsonin; activates complement *Most important in secondary response |
|
|
Describe IgM:
heavy chain type? subclasses? 2 special features/functions? 3 |
IgM
Mu (μ) heavy chain Monomeric IgM found on B-cells; Pentameric form secreted by plasma cells First class produced during a primary immune response and is important in early stages of humoral immunity. *Good complement fixing antibody *First Ab that's generated in fighting an infection |
|
|
Describe IgA:
heavy chain type? 2 subclasses? special features/functions? 3 |
Alpha (α) heavy chain
Serum IgA exist as a monomer (10-15% of Ig in serum) *Most predominant isotype in secretions (tears, saliva, milk, etc.); here it exists as a dimer with J chain and secretory component Important in mucosal immunity |
|
|
Describe IgE:
heavy chain type? How much is in serum? Function? |
Epsilon (ε) heavy chain
Very low levels in serum Mediates allergic reactions, may defend against certain parasites (e.g. worms) *Think parasites. Effective at fighting parasites via ADCC. |
|
|
Describe TCRs:
|
T cells mature in the thymus.
Most T cells see only peptides. *Like antibodies, each chain has a variable and constant region. The variable regions contain CDR. *Like BCR, TCR undergo gene rearrangement (Mix-and-Match) prior to expression. All express two chains. 95% express alpha and ß chains. Others express gamma and ∆ chains. |
|
|
2 key ∆s b/t B and T cells:
|
-B cells can export (secrete) their receptors in the form of antibodies, but the TCR stays tightly glued to the cell surface.
-The spectrum of antigens recognized by TCR is MHC restricted! |
|
|
Explain the role of CD4+ and how it relates to a TCR:
|
It's a co-receptor. Binds to the MHC II PRO on an APC at the ß2 domain.
|
|
|
Explain the role of CD8+ and how it relates to a TCR:
|
It's a co-receptor. Binds to the MHC I PRO on an APC at the alpha3 domain.
|
|
|
How does clonal selection occur in B and T cells?
|
Clonal Selection Principle:
When a pathogen antigen enters the body for the first time, only those B or T lymphocytes bearing receptors specific for that antigen are selected to proliferate. As a result, a clone of B or T cells with identical antigen specificities is produced. |
|
|
How is the enormous diversity of BCR and TCR produced?
|
Somatic recombination ; “MIX and MATCH” Modular Design
-Generates antigen receptor diversity. -Occurs before the T or B cells encounter antigen. -Gene rearrangement process that randomly recombines the gene segments that encode the variable regions of the BCR and TCR proteins. |
|
|
VDJ recombination:
|
-On genes coding for antibodies and BCR/TCRs, there are regions that are V-variable, D-diversity, and J-junction (as well as the constant regions).
-These are the modules that are mixed/matched to eventually be translated into the variable arms of the BCRs/TCRs. |
|
|
DESCRIBE THE STEPS OF SOMATIC RECOMBINATION AND EXPRESSION OF GENES FOR BCRS/TCRS/ABS:
-6 big picture levels |
1) Germline DNA
2) Recombined DNA in two B/T/Ab cell clones -D and J come together randomly -V segment recombines with them (V-DJ joining) 3) 1˚ RNA transcript 4) mRNA 5) Two of one chain are created! |
|
|
What processes generate diversity in B/T/Abs? 2
|
Combinatorial Diversity
Junctional Diversity |
|
|
Junctional Diversity:
|
Adding or removing nucleotides at the V-DJ junction
*This actually accounts for more diversity than does combinatorial diversity. |
|
|
What's 'more' diverse- the heavy or light chains on B and T cell receptors? Why?
|
Heavy chains--they contain the D regions.
|
|
|
What happens to most pro- B/T cells in the early stages of maturation/selection?
|
-They die off due to failure to express BCR/TCRs.
-Gene sequences for the receptor are not in frame --> apoptosis. |
|
|
What is positive vs. negative selection and where does it happen with T cells?
|
*This occurs in the thymus.
-Positive selection results in MHC restriction (ensures WEAK self antigen recognition); requires 'TEACHING' by cortical TECs and interdigitating dendritic cells. They present self-antigens to the developing cells and see which ones can recognize them appropriately. -Negative selection results in self-tolerance (T cells with STRONG self antigen recognition get apoptosed). 96% die! -Death by Neglect for T cells with NO self antigen recognition. |
|
|
What happens to newly positively selected T cells in the thymic cortex?
|
-CD4+ or CD8+ T cells migrate to medulla
-They are then exposed to AIRE+ (autoimmune regulator) medullary thymic epithelial cells (mTEC), which express tissue specific antigens and mediate another round of negative selection. -Those that survive are released into the periphery. They are FULLY MATURE but ANTIGEN NAIVE at this point. |
|
|
Summary of the processes of + and - selection of T cells:
|
|
