B cell mediated immunity 1 Flashcards
What is the sole function of the B cell arm of the adaptive immune system?
Antibody production
What is the role of the Abs?
bind tightly to pathogens
The most efficient antibodies are those that do what 2 things?
- produced early in infection,
- bind antigen with high affinity
the onset of antibody production is delayed for about a week after onset of infection. Why?
B cells typically do not differentiate into plasma cells unless they have received T cell help
it takes time for B cells to undergo isotype switching and affinity maturation
Why is isotype switching and affinity maturation important?
they produce high affinity antibodies that direct the proper effector mechanisms for most efficient clearance of the pathogen
the effectiveness of the antibodies produced increases over the course of the response.
The high affinity Abs are retained how? why?
retained in the form of memory B cells that provide long-lived immunity to re-infection.
following secondary exposure to a pathogen, the B cell response should be what?
very efficient because high-affinity B cells of the proper isotype have already been clonally expanded and can be quickly reactivated following re-infection.
B cell activation requires what?
BCR crosslinking
this clustering/aggregation of BCRs results in signaling to the inside of the cell. How is it done?
upon binding to antigen (protein or carbohydrate), the surface IgM molecules (BCRs) become physically crosslinked to each other and are drawn into the localized area of contact with the antigen;
What is the BCR composed of?
- a single antibody molecule (the isotype that is produced by that B cell) that is associated with two protein chains: the immunoglobulin alpha and Beta chains (Ig-a and Ig-B)
the Ig-a and Ig-B chains serve as what of the B cell receptor. What is this analogous to on the T cell?
the signal transduction unit
analogous to the CD3 complex expressed by T cells
How does the signal transduction unit (Ig-a / Ig-B chains) of the BCR initiate intracellular signaling pathways?
the cytoplasmic tails of Ig-a and Ig-B have immunoreceptor tyrosine-based activation motifs (ITAMs)
- ITAMs become clustered (due to receptor crosslinking),
- tyrosine residues within these motifs become phosphorylated,
- tyrosine kinases are activated,
- intracellular signaling pathways are initiated
What is the B cell co-receptor?
a complex of at least 3 proteins
- complement receptor 2 (CR2 or CD21) which binds to complement components that are bound to the surface of a pathogen;
- CD19, which acts as the signaling chain of the co-receptor;
- CD81 (or TAPA-1) whose function is unknown (likely involved in signal transduction)
What acts as the signaling chain of the co-receptor?
CD19
What is the result when the B cell co-receptor is engaged?
- cytoplasmic tail of CD19 becomes phosphorylated, allowing it to bind to intracellular signaling molecules which generate signals that synergize with those generated by the BCR complex,
- resulting in a 1,000-10,000-fold increase in signaling
T/F signaling through the BCR in combination with signaling through the B cell co-receptor will induce activation of the naïve B cell
false, signaling through the BCR in combination with signaling through the B cell co-receptor is generally still insufficient to induce activation of the naïve B cell
How is a naive B cell activated?
signaling through BCR along with B cell co-receptor
a second signal of activation derived from helper T cells are also required
many antigens require help from what to elicit B cell responses? What type of antigens are these referred to?
an antigen-activated effector CD4+ T cell (helper T cell)
referred to as thymus-dependent antigens (TD antigens)
some antigens can activate B cells in the absence of T cell help; such antigens are referred to as what?
TI antigens
bacterial cell walls and capsules contain (or are composed of) what?
complex polysaccharides, lipopolysaccharides, and proteoglycans that are chemically and antigenically distinct from any antigens derived from mammalian cells
Why are the bacterial macromolecules (complex polysaccharides, lipopolysaccharides, and proteoglycans) major targets of Ab response?
often characterized by repetitive epitopes and serve as major targets of the antibody responses produced against extracellular bacterial pathogens
For TI antigens, what is the reason no T cell help occur?
The bacterial and capsule components cannot be processed and presented to T cells bc they are non-protein
for thymus-independent antigens, the need for T cell help can be overcome in two different ways. name them
- TI-1 antigens have an intrinsic capacity for inducing B cells to proliferate
- TI-2 antigens are typically composed of repetitive carbohydrate or protein epitopes present at high density on the surface of a microorganism
What provides the intrinsic capacity for TI-1 antigens to induce B cells to proliferate?
- TI-1 antigens bind to BCR, but also engage other receptors on the surface of B cells whose stimulation promotes proliferation and differentiation
- at high [], TI-1 antigens can activate almost any B cell, regardless of the BCR specificity (non-specific activation)
- antigens that cause such polyclonal activation of B cells are known as B cell mitogens; an example of a B cell mitogen is lipopolysaccharide (LPS), which is a common component of Gram-negative bacteria
- •• the concentration of antigen required to polyclonally activate B cells is much higher than is normally encountered during a natural infection; during an infection, the B cell mitogen concentration is sufficient to activate only those B cells that have been engaged through their BCRs by their specific antigen, and therefore, only antigen-specific B cells will be activated