Lecture 6 - Ab structure Flashcards
What is adaptive immunity?
“acquired immunity”, specific response to antigenic challenge
What is adaptive immunity?
“acquired immunity”, specific response to antigenic challenge
What is it mediated by?
antigen-specific lymphocytes and/or their products
-two arms: humoral and cell-mediated immunity
What is it mediated by?
antigen-specific lymphocytes and/or their products
-two arms: humoral and cell-mediated immunity
What is also associated with adaptive immunity?
immunologic memory
What is also associated with adaptive immunity?
immunologic memory
True or False: adaptive immunity doesn’t coordinate with innate immunity
False
True or False: adaptive immunity doesn’t coordinate with innate immunity
False
Describe different pathways of immunity activation
- Innate –> infection –> recognition by non-specific effectors –> pathogen clearance
- Early induced –> infection –> recruitment of effector cells –> activation of effector cells –> pathogen clearance
- late adaptive –> infection –> Ag transport to lymphoid organs –> recognition by naive B and T cells –> clonal expansion of B and T cells –> pathogen clearance
Describe different pathways of immunity activation
- Innate –> infection –> recognition by non-specific effectors –> pathogen clearance
- Early induced –> infection –> recruitment of effector cells –> activation of effector cells –> pathogen clearance
- late adaptive –> infection –> Ag transport to lymphoid organs –> recognition by naive B and T cells –> clonal expansion of B and T cells –> pathogen clearance
What is protective immunity?
re-infection –> recognition by preformed Ab and effector T cells –> pathogen clearance
What is protective immunity?
re-infection –> recognition by preformed Ab and effector T cells –> pathogen clearance
What does immunological memory look like?
re-infection –> recognition by memory B and T cells –> rapid expansion to effector cells –> pathogen clearance
What does immunological memory look like?
re-infection –> recognition by memory B and T cells –> rapid expansion to effector cells –> pathogen clearance
When is Ab production initiated?
3-7 days after initial exposure to Ag and only if innate immune processes fail to clear it rapidly
When is Ab production initiated?
3-7 days after initial exposure to Ag and only if innate immune processes fail to clear it rapidly
What are Ab?
also called immunoglobulins; antigen-specific products of B cells
- principle mediators of adaptive immunity and production of appropriate Ab response to infection (major contributor to immunity)
- secreted proteins found in plasma and on mucosal surfaces at varying concentrations
What are Ab?
also called immunoglobulins; antigen-specific products of B cells
- principle mediators of adaptive immunity and production of appropriate Ab response to infection (major contributor to immunity)
- secreted proteins found in plasma and on mucosal surfaces at varying concentrations
What do Ab do?
- interact with Ag non-covalently
- heterodimeric proteins produced by B bells
- divalent
- bifunctional
- fn in many environments
What do Ab do?
- interact with Ag non-covalently
- heterodimeric proteins produced by B bells
- divalent
- bifunctional
- fn in many environments
What do different constant regions divide Ig into?
classes or isotypes (IgMM, IgG, IgE, IgA)
What do different constant regions divide Ig into?
classes or isotypes (IgMM, IgG, IgE, IgA)
What is the Ab structure?
- all have same basic structure: 2 Identical light chains and 2 Identical heavy chains
- subunits are covalently linked
What is the Ab structure?
- all have same basic structure: 2 Identical light chains and 2 Identical heavy chains
- subunits are covalently linked
What does heavy subunit determine?
Ig class (isotype)
What does heavy subunit determine?
Ig class (isotype)
How are distinct Ab regions determined?
by protease digestion
Fc portion - contains heavy chain constant region
Fab portion - contain Ag finding site
How are distinct Ab regions determined?
by protease digestion
Fc portion - contains heavy chain constant region
Fab portion - contain Ag finding site
Different regions of the Ab molecule have been defined by what?
proteolytic digestion and function; VH, VL, CH, CL
What is the Ag binding pocket formed by?
variable regions of the Ab H and L chains –> encoded by multiple gene segments
What does this variable region that forms the binding pocket undergo?
mutation to generate Ag binding pockets of varying strength
What does the binding pocket interact with?
an epitope in a non-covalent manner
True or False: all Ab are multivalent
True
If Ab are multivalent, what can happen?
Ab can bind two of the same epitopes on a signle Ag or two of the same epitopes on two different Ags
Ab differences are denoted based on what?
the nature of the differences
Give examples of Ab differences?
- Isotypic differences: IgG vs IgA - could be same binding pocket but Ab end up in diff place
- Allotypic differences: different alleles of the Ab chains - two IgG1 mols
- Idiotypic differences: diff specificities for epitopes they bind (come together differently) - two IgG mol, different Ag specificities
What’s the difference btw B cells and plasma cells?
Plasma cells are B cells; B cells have Ab on their cell surface; plasma cells secrete Abs
-B cells mature into plasma cells, some proliferate into B memory cells –> store in lymphoid tissue
What’s the first Ab to be secreted by B cells?
IgM; immature B cells secrete IgM (in bone marrow) as monomers –> after maturing and being activated by an Ag, IgM are secreted as pentamers
B cells leave lymphoid tissues secreting what?
IgM
What Abs are secreted onto mucosal surfaces?
IgM and IgA
IgM and IgA (on mucosal surfaces) are protected from degradation by what?
by binding to J chain; IgM forms a pentamer, while IgA forms a dimer
- This covalent link with the J chain occurs within the B cell
- This occurs after being activated by an Ag
Since the covalent link with the J chain occurs within the B cell, what does this mean?
the Ag specificity of each Ag-binding site is identical for a give IgM pentamer of IgA dimer (respectively)
What is the J chain used for?
transporting dimeric IgA across epithelial barriers to coat mucosal surfaces
What determines the Ab class or isotype?
constant region of the heavy chain
What does the variable region confer?
epitope specificity
What does the constant region confer?
functional capacity
Give examples of functional capacities
IgG and IgM activate pathway for complement
IgE bidns to mast cells and basophils
True or False: relative expression of each isotype varies
True; depends on location for what Ab has highest [ ]
What’s the ratio of relative expression of Ab isotypes
IgG>IgM>IgA in blood
IgA»IgM>IgG on mucosal surfaces
What does allelic exclusion result in?
only one chromosome rearrangement per cell
Describe the major Ab isotype for each fn/activity (neutralization, opsonization, NK cell activation, mast cell activation, complement activity, crosses epithelium crosses placenta, extravascular diffusion, highest in serum level/half-life)
Neutralization - IgG and IgA Opsonization - IgG NK cell activation - IgG Mast cell activation - IgE Complement activity - IgM and IgG Crosses epithelium - IgA Crosses placenta - IgG Extravascular diffusion - IgG and IgA Serum level - IgG Serum half-life - IgG
When are other isotypes (besides IgM) secreted?
later depending on what cytokines it interacts with –> can rearrange and make other isotypes other than IgM
What Ab isotypes do these cytokines induce production of (IL-4, IL-5, IFN-gamma, TNF-alpha)?
IL-4 –> induces IgG and IgE
IL-5 - augments production of IgA
IFN-gamma - induces IgG and IgG
TNF-alpha - induces IgG and IgA
Different Ab isotypes have different what?
functionalities for immune response
ex: heavy chain of IgG is recognized by receptors on phagocytes
- mast cells have receptors for IgE
- IgA is secreted across epithelial layers to provide protection at mucosal surfaces
What is a well documented Ab deficiency in humans?
IgA deficiency; no surface Ab in lungs –> susceptible to URI
-similar condition identified in laboratory beagles and a colony of cocker spaniels
What does the “hinge” covalent bond btw constant heavy regions help with?
giving flexibility
Define major functional properties of these Ab (IgM, IgG, IgA and IgE)
IgM - antigen receptor of naive and some memory B cells
IgG - transfer of adaptive immunity to offsprign, regulation of Ab production
IgA - protection of mucosa, protection of newborn mucosa via milk
IgE - activation of mast cells and basophils
Each B cell makes a unique receptor generated via what?
rearrangement and mutation of the germline DNA
what is agglutination?
reduces number of infectious untis to be dealt with (Ab bind multiple antigens)
What is opsonization?
coating Ag with Ab enhances phagocytosis (several Ab on 1 Ag)
What is activation of complement?
complement cascade –> causes inflammation and cell lysis
What is Ab-dependent cell-mediated cytotoxicity?
Abs attached to target cell cause destruction by macrophages, eosinophils and NK cells
What is neutralization?
blocks adhesion of bacteria and viruses to mucosa (Ab blocks all attachment sites on Ag)
What is structure of IgG, IgM and IgA?
monomer, pentamer, dimer
What is percentage of total serum Ab for IgG, IgM and IgA?
80%, 5-10%, 10-15%
What is half-life in serum of IgG, IgM and IgA?
23 days, 5 days, 6 days
Is there placental transfer for IgG, IgM and IgA?
yes, no, no
known functions of IgG, IgM and IgA?
enhances phagocytosis, 1st Ab production in response to initial infection,, localized protection on mucosal surfaces
How do B cells develop receptors (Abs) that can bind to almost any epitope?
Region of Ab gene that binds the epitope is generated by a semi-random rearrangement of gene segments, thus creating different exons for the Ab chains within each B cell
