Lecture 9- B Cell Response to Antigen Flashcards
T-cells are only able to recognize peptides presented on a ____.
MHC
What are thymus-independent antigens?
antigents that do not have proteins
do NOT need the help of T cells for activation of B cells
What are thymus-dependent antigens?
antigens that have proteins
needs T cells help for B cell activation
B cells can recognize what type of antigens?
- Whole antigens & pieces of antigens
- Thymus-independent
- Thymus dependent
Most pathogens have ____ types of antigens and stimulate ___ responses.
- thymus-independent + thymus-dependent;
-Stimulate both responses
What are examples of thymus-independent antigens?
(non-protein)
- polysaccharides, lipids, nucleic acids
What are the 2 methods of B cell activation during a T-independent reaction?
- B cell receptors cluster due to multiple epitopes present on the Ag (multivalteny Ag)
- Other molecules present on the Ag, such as TLRs (toll-like receptors), interact with the B cell and stimulate it
What IgGs are produced during T-independent B-cell activation?
- IgM (main)
- IgG (small amnts)
During T-independent co-stimulation/ antigen interaction, CD21(CR2) binds to ____.
- C3d (tagged antigen)
During T-independent co-stimulation/ antigen interaction, CD21(CR2) PRODUCES:
- CD81
- CD19
(accessory molecules)
(this forms the CD21/CD19/CD81 complex)
BCR binding (with costimulation CD21) initiates:
receptor-mediated endocytosis, enzymatic degradation, and display of peptide-antigen on MHC 2
CR2 is also known as ____.
CD21
The clustering of bound BCRs initiates the phosphorylation of _____.
ITAMS (immunoreceptor tyrosine-based activation motif)
What are the 4 results of T-independent B cell activation?
- Clonal expansion
- Some memory B cells
- Little/no isotope switching (so mainly IgM is produced)
- Little/no affinity maturation
How is a t-dependant B cell response initiated?
- The B cell interacts with Ag that is either free-floating or attached to a pathogen
- It internalizes the antigen through endocytosis (has to extract Ag if it is on a pathogen)
- The antigen is processed and presented through the MCH-peptide complex
- Helper T cells will recognize MHC 2 and bind to it, which activates the B cell
B cells express _____, which binds to ___ located on helper T cells. This activated the B cell (co-stimulation)
B cells: CD40
T cells: CD40L
B7 interacts/binds with ____ on helper T cells
CD28
T-dependent co-stimulation promotes:
- B-cell activation
- Isotype switching
- Other APC functions
What happens when there is a deficiency in CD40L?
Hyper IgM syndrome
(If there is not enough CD40L, class switching for the B cell does not occur, leading to an excessive amount of IgM)
What does the binding of B7 and CD28 do?
It prevents anergic behavior of the B-cell
(Which prevents unresponsiveness to antigens)
IL-4 by itself will stimulate:
class switching to IgE
IL-4, along with IL-2, will result in:
B-cell proliferation
IL-4, along with IFN-gamma, will stimulate:
classs switching to IgG
IL-5 by itself will result in:
- B-cell differentiation into plasma cells
- activation of eosinophils
IL-5, along with TGF (transforming growth factor) & BAFF (b-cell activating factor), leads to:
class switching to IgA
IL-6 by itself will result in:
B-cell differentiation into plasma cells
T-dependent B-cell activation induces a ______ ______ response.
germinal center
How long do short & long-lived plasma cells live?
- Short: a few days
- Long: 1-2 weeks
What type of B cell activation do short-lived plasma cells have?
T-dependent and T-independent
Short-lived plasma cells mainly secrete ____ (Ig).
IgM
Where are short-lived plasma cells located?
- red pulp of spleen
- medullary cords of lymph nodes
What is the cell pathway of humoral immunity?
- Naive B cells become activated
- Activated B cells differentiate into plasma cells
- Plasma cells secrete antibodies
What is the affinity for antibodies for short & long-lived plasma cells?
- Short: low affinity
- Long: high affinity (they have undergone class switching- have somatic mutations and affinity maturity as well)
What type of B cell activation do long-lived plasma cells have?
ONLY T-dependent
Long-lived plasma cells secrete _____.
many different antibodies
Where are long-lived plasma cells located?
- bone marrow
- mucosal tissues (GIT)
- lactating mamary glands
Where do long-lived plasma cells arise from?
- germinal center (primarily)
- memory B cells (secondary)
Primary immune response starts with:
The activation of a single cell, which then undergoes mitosis (differentiating into memory and effector cells)
What are the 6 steps in a primary response?
- Single cell is activated
- Cell undergoes mitosis & differentiates into memory & effector cells
- IgM is secreted first by some effector cells (t-independent)
- Other cells continue mitosis and undergo class switching to IgA or IgG (T-dependent)
- IgG becomes more evident
- Some later cells become memory cells committed to producing IgG
What are the 2 steps in a secondary response/encounter?
- Some effectors cells still produce IgM
- Memory cells produce IgG, IgE, or IgA depending on the antigen type
(More Ig committed cells, higher IgG, higher titre, and higher affinity abs)
What changes in the BCR during isotype switching?
The constant portion of the heavy chain
(variable portion stays the same- so specificity stays the same)
Where does affinity maturation take place?
The germinal centers
Affinity maturation is the result of _______, followed by:
- result of somatic hypermutation
- followed by positive selection of high affinity B-cells
High affinity B-cells give rise to:
Long-lived plasma cells and memory B-cells
When are memory B cells generated?
during the primary response
Do memory B cells secrete antibodies?
no
Memory B cells circulate in the _____ form.
inactive
The majority of memory B cells are T-________ with ______ affinity.
T-dependent; high affinity (due to isotope switching)
(some are T-independent)
How long do memory B cells circulate?
from months to years in the absence of an antigen (long-living)
Memory B cells are important in the:
recognition & response to repeat exposure of the same antigen
(assumed to have specific differences that increase clonal expansion & have faster differentiation into plasma cells, which can secrete antibodies
What transports maternal IgG?
the neonatal Fc receptor
What can maternal IgG cross?
- the placenta into the fetus
- the GI epithelium of the neonate when ingesting colostrum
The neonate will get _____ immunity for about 3-4 months before the maternal antibodies die
passive
sldie 12
What are the functions of IgG?
- Agglutination
- Opsonization
- Neutralization
What are the functions of IgA?
- Agglutination
- Neutralization
What are the functions of IgM?
- Agglutination
- Neutralization
Which Ig fixes complement?
IgM
Which Ig is key for allergic reactions and multicellular parasites?
IgE
What is the first antibody produced?
IgM
ADCC-coating (antibody-dependent cellular toxicity) of a microbe in antibodies leads to ___ _____.
cell lysis
Which Ig is not very significant except in BCR & B-cell maturation?
IgD
Which Ig is most abundant & able to cross the placenta & GI tract when in colostrum?
IgG
Which Ig is important in mucosal immunity & found in secretions?
IgA
Which antigen type can thymus-dependent respond to?
proteins
Which thymus response has co-stimulation with CD21 binding to C3d, CD81, and CD19?
Thymus-independent
What happens during neutralization?
Antibody binds to microbes, which prevents them from binding to and infecting host cells
Intracellular microbes released from an infected cell are bound & prevented from infecting adjacent host cells
Antibodies bind to microbial toxins → Prevent the toxin from binding to host cells
What is opssonization?
Mediated phagocytosis
Antibodies coat/opsonized microbes
- Fab portion of antibody binds to microbes
Fc portion of these antibodies bind to Fc-gamma receptors on phagocyte
Leads to ingestion of opsonized microbe ‘
IgG
Where is ADCC (Antibody-dependent cellular cytotoxicity) seen?
in NK cells and other WBCs
ADCC
IgG antibodies bind & coat infected host cells
The NK cell recognizes such antibody-coated host cells
- Binds to the Fc receptor of bound IgG
- Destroys the coated host cells
