11 - B-Cell Flashcards
Plasma B-Cell
Surface AB’s / Markers ?
Location?
CD27 + NO SURFACE AB’s
since job is to produce AB’s
Made IN THE TISSUE:
MALT
Lymph Node Germinal Center
Splenic Marginal Zone
Travel & Reside in:
MALT / Other Nodes / Bone Marrow
Memory B-Cell
Surface AB’s / Markers ?
Location?
CD27** + **IgG** + **IgA** + **IgE
CD19 / CD20 / CD21
GAE-19-20-21
Generated in:
MALT / Lymph Node Germinal Center
Travel & Reside in:
TISSUE only (MALT, etc)
B-Cell
Surface AB’s / Markers ?
Location?
CD19 / CD20 / CD21
MHC2
Surface Ab = IgD / IgM
Generated in:
Bone Marrow
Travel & Reside in:
MALT / Lymph node Germinal Center / Splenic Marginal Zone
Naive B-Cell’s BCR
In bone marrow,
Naive B-Cell –> selects BCR to display on surface
- *BCR** = Membrane Bound Antibody
- *IgM** or IgD
Has, ~1000 identical BCR on surface –> recognize the SAME Ag
BCR + CoReceptor Complex
- *Coreceptor Complex** modulates the
- *BCR SIGNAL TRANSDUCTION**
CD81
CD21
binds opsonized antigenic particles
CD19
primarily responsible for Signal Transduction
What can Naive B-cells BCR bind to?
AG = ANY ORGANIC MOLECULE
binding occurs in the Lymphoid Tissue
>99% of Naive B-cells circulate their whole lives w/o encountering Ag –> die within a fiew days
T-Cells can only interact with PROTEINS
Thymus-Dependent (TD) Ag
Naive B-Cell Activation
&
Location
PROTEIN Ag
that require activation guidance by the CD4+ Th Cells
Require 3 Signals for activation via TD Ag:
BCR -> AG
Costimulatory SIgnal
Cytokine Signal
Anatomically restricted to:
LYMPH Node Germinal Center & MALT
Thymus INDependent (TI) Ag
Naive B-Cell Activation
&
Location
POLYMERIC Ag
that crosslinks the BCR & directly activate B-cell
Location determines type of immune response:
SPLENIC Marginal Zone
TD Ag Activation
Response?
Produces What?
Thymus Dependent Naive B-Cell Activation
PROTEIN-Ag
Response is Delayed = 5-15 days
Generates more than 1 Ig Isotype:
- *IgM** and
- *IgG** or IgA or IgE
Antibodies produced are:
Specific for 1+ epitope of a particular antigen
Memory Cells are GENERATED
(3-7 day secondary response)
Th-Bcell Cooperation
TD Ag Activation
Thymus Dependent Ag B-cell Activation
LInked Recognition Phenomenon
- *BOTH** the Th & B-cell must be
- *activated & interact** for AB production
The Antigenic Peptide to which the TCR binds
is NOT necessarily IDENTICAL to the protein to which the BCR binds
As long as the TCR is specific for ONE of the PEPTIDE fragments derived from the degradation of the AG
V
B-Cell Will be Activated
3 Signals of
Thymus Dependent Ag B-cell Activation
Signal 1
BCR -> AG
for initiation of B-Cell PROLIFERATION
Signal 2
COSTIMULATION
provided by the CD4+ Th Cells via CD40L/CD40 bound
Signal 3
CYTOKINES
secreted by the activated Th
Costimulatory Pairs
BCR
CD40 / CD40L (CD154)
B7/CD28 = Activate the T-cell
Following BCR ligation, the decision between
Activation vs Remaining Inert depends on the:
Amount / Avidity / Timing
of interaction, and by the:
Nature & Amount of Costimulation present
- *CD40/CD40L**
- *Effect on B-cell**
Costimulatory Pairs
Promotes Up-regulation of B7 on B-cell
Promotes B-Cell Proliferation
Promotes SOMATIC HYPERMUTATION
–> affinity maturation –> more specificity / stronger binding
Requires for AB “Class Switch”
IgMfirst –>IgA/IgE etc
Promotes Memory B-cell Formation
CD40/CD40L
Effect on T-cell
IL4 / IL5
Promotes Th cell to secrete cytokines that promote:
Growth & AB production
by the activated B-cell
PRIMARY TD Ag B-cell Activation
Ag Recognition –> Proliferation
each cell growth cycle + division takes about
12 hours x 7 days
- *20K B-cell clones** are produced with:
- *IDENTICAL Ag-Specific Ig receptor**
After Proliferation:
B-cell starts its Effector Fxn –> Ab Production
2000 Antibodies / Second
dies after 1 week
SECONDARY Response
Thymus Dependent Ag B-cell Activation
BOTH B & T-cells have to been previously activated & expanded
SAME EPITOPES
must be presented to B & T-cell for secondary response to occur
Ag Presentation by Bcell is accompanied by:
- *Paired interaction** @ surfaces of B+Tcells
- *Cytokine Secretion** by T-cells
TI Ag Activation
Thymus IndePendent Ag Activation
What does it Produce?
& WHERE?
does NOT require Th cell help to make Ab
RAPID response= <2 days of Ag encounter
Produces:
ONLY IgM
in the:
MARGINAL ZONE OF THE SPLEEN
A crucial first response to pathogens
- no Class Switching*
- no immunologic Memory* (need Th for Memory cells)
T1-1 Ag
1 of 2 Types of Thymus Independent Antigens
TI-1 = MITOGENS
Able to activate Multiple Different B-Cell Clones
to Produce AB’s = Polyclonal response
Ex.
- *liposaccharide** derived from bacterial cell wall
- *protein coats** of some viruses
TI-2
1 of 2 Types of Thymus Independent Antigens
TI-2
Multiple / Repeating / Identical Epitopes
Polymeric Protein of:
Bacterial Flagellin
Bacterial + Fungal POLYSaccharides
Nucleic Acids
Binding results in:
CROSSLINKING of multiple BCR’s
TI-Type 1 Ag ACTIVATION
1 of 2 Types of Thymus Independent Ag Activation
- *Mitogens** can activate Multiple B-cells
- -> abnormal POLYCLOAL activation
- Does NOT have a very good response*
Signal #1
- *BCR** –> Polymeric Ag
- Mitogen –> BCR** as the first signal, *BUT _NON-SPECIFICALLY_
Signal #2
from TLR’s that respond to mitogen
TOLL = pattern recognition receptor on B-Cell
–> cell division + AB production
TI-Type 2 Ag ACTIVATION
1 of 2 Types of Thymus Independent Ag Activation
Has many Clinical Apps in VACCINATIONS:
Many bacteria have polysaccharide capsules
HIV is a highly glycosylated protein
Signal #1
BCR –> AG w/ multiple/repeating/identical epitopes
Bacterial flagellin / Poly saccharide
Signal #2
provided by Clustering of BCR
not really needed, there is enough signal w/ all the binding
KEY Features of
TI-Ag B-Cell Activation
Essentail in recognition of Non-Protein Ag
Anotomically restricted to Marginal Zone of Spleen
Activate B-Cell in ABSENCE of CD4+ Th Cell
IMMEDIATE response, don’t need Th activation
Generate primarily ***_LOW_* _Affinity IgM Ab's_** *no class switch / no affinity maturation*
limited ability to generate memory cells
not developed until 2nd year of life
TD Ag Activated B Cell Maturation Events
ONLY OCCUR in the case of THYMUS DEPENDENT Ag Activation
Th interaction –> FULL B-cell activation
through secreted Cytokines & costimulation (CD40-CD40L)
1 = Class Switching
Changes the CLASS/FXN of AB, but not Ag specificity
Fab region = unchanged // Fc region changes
- *2 = Somatic Hypermutation**
- *affinity maturation**, BCR affinity to Ag increases
3 = Differentiation
into a Ab-producing plasma cell or memory B-cell
Which Antibody Isotype has these Functions?
Opsonization
Crosses Placenta
provides immunity for BABIES
IgG
involved in ALL parts of HUMORAL Immunity
Also:
Complement activation
Agglutination
Neutralization
Which Antibody Isotype has these Functions?
Complement Activation
Agglutination
Neutralization
IgM
Which Antibodies can do this?
Inactivation of Viruses
&
Neutralization of Bacterial Toxins
IgG
is invovled in ALL humoral Immunity
IgM** & **IgA
Which Antibodies can do this?
Clumping / Agglutination
IgG
is invovled in ALL humoral Immunity
IgM** & **IgA
Which Antibodies can do this?
Ag-AB complex formation –> COMPLEMENT fixation –> lysis
Destruction by non-specific immune system cells
IgG
is invovled in ALL humoral Immunity
IgM
Which Antibody can do this?
Macrophages have Fc receptors –> Enhanced Phagocytosis
= OPSONIZATION
ONLY IgG
is invovled in ALL humoral Immunity
Negative Regulation
of the Humoral Immune Response
3 Mechanisms
- *Ab Eliminates Ag Source**
- -> no more stimulation
Inhibit B-Cell Activation
When there is ENOUGH soluble AB-Ag complexes
Terminates B-Cell Activity
Clustering of membrane Ig + Fc Receptor on surface of B-cell activates a inhibiatory signaling cascade
