Transcript 9th seminar Adaptive immunity

B and T cell functions
ADAPTIVE IMMUNITY
Humoral immunity/ Antibody-mediated immunity (B cells)
1: processing of a pathogen by an antigen presenting cell and presentation of it on class II MHC
molecules to an antigen-specific helper T cell activates the helper T cell to produce cytokines IL-2,
IL-4 and IL-5. These cytokines activate a B cell having that same antigen-specific receptor to
produce antibodies against that particular antigen.
2. An alternative pathway of B cell activation is the T-independent way, involving no helper T cells
and thus no IL-4 and IL-5. It requires receptor aggregation or a strong cross linking of BCR with
other PRRs.
Cell-mediated immunity (T cells)
1: A bacrteria taken up by a macrophage, degraded and is presented on class II major
histocompatibility complex proteins (MHC II) that interacts with the specific antigen-specific
receptor on a helper T cell, this activates the T cell to proliferate and produce cytokines (IL-2, IFN-γ).
2: A virus infects cells of the respiratory tract, a viral particle is presented on class I MHC proteins
and recognized by an antigen-specific receptor on a cytotoxic T cell it then proliferates with the help
of IL-2 from helper T cells, and specifically kill the virus infected cells.
Humoral Immunity
Cell-Mediated Immunity
Microbe
Extracellular bacteria
Processed by an APC
Extracellular microbes
phagocytosed in a
macrophage
Intracellular microbes
replicating in infected
cells
Responding
lymphocyte
B lymphocytes
T lymphocytes
T lymphocytes
Cell Interactions
Cytokine secretion
T-dependent: APC MHC IITCR and IL-10 production.
Naïve CD4+ T cell  Th2 cells
secreting IL-2, IL-4 and IL-5 
B cell Plasma cell
APC MHC II-TCR and IL12 production.
Naïve CD4+ T cell  Th1
cells secreting IL-2 and
IFNγ  macrophage
activation
APC or virus infected
cell presents Ag on
MHC I to TCR.
Naïve CD8+ T cell 
CTL (cytotoxic T
lymphocyte)
Activation of
macrophages- microbial
killing
Lytic granules
(containing granzymes
and perforin) and FasL
expressionLysis of infected cells
*T-independent: BCR
aggregation or cross linking
Effector mechanism
Secreted antibodieselimination of bacteria
T cell migration and activation
T cell activation can be induced by antigens in the presence of accessory cellsthe APCs (not by a soluble antigen) or viral antigens on an infected cell
Naïve T cells first encounter antigens
presented by DCs in the SLO
A. Naïve T cells entry from blood to lymph nodes via high endothelial
vanules (HEV) is dependent on adhesion molecules and CCR7.
Encounter with an Ag presenting DC coming from the afferent
lymphatics will increase the chemokine receptor expression on the
effector T cells. B. this will guide them to enter the inflamed tissue from
the blood.
THE IMMUNOLOGICAL SYNAPSE
APC
T
Second signals triggered by co-receptors are required for
T-cell activation
Th
Th
Th
CD40L
CD28
CD40
B7
B7
ACTIVATION
Phases of T cell response
Effector T cells
The three types of effector T cell produce
distinct sets of effector molecules
Naïve T-cells differentiate into various
effector cell types
Key step in Th1 differentiation is the
production of IL-12 by Macrophages or
DCs that will result in the INF-γ
production by the T cells and NK cells.
A key step in Th2 differentiation is the
production of IL-4 by Mast cells and
eosinophil granulocytes then later the T
cells join to produce IL-4.
A key step in Th17 differentiation is the
production of IL-1, IL-6 and IL-23
by DCs + TGFβ.
Absence of IL-4 and INF-γ.
A SEGÍTŐ T LIMFOCITA ALPOPULÁCIÓK KÜLÖNBÖZŐ
ANTIGÉN PREZENTÁLÓ SEJTEKKEL MŰKÖDNEK EGYÜTT
B7 expression  antigen presentation
Csíraközpont kialakulása
Affinity maturation
Th2
B
Isotype switch
Memória B sejt képződés
IL - 4
B7 expression
DC
MΦ
Th1
IFNγ
 antigen presentation
MHC-II expression  antigen presentation
Érett dendritikus sejt
Macrophage activation
IL-12 helps Th1 cell differentiation
Virus, bacteria,
protozoa, fungi
NK cell
IL-12
IFNγ
Th1
IL-2
IFNγ
TNF-β
GM-CSF
IL-3
DC
MΦ
CD8+ cytotoxic T cell
IL-12
IFNγ
IL-12
Th0
Th2
IL-4
IL-5
IL-10
IL-13
IL-10 helps Th2 cell differentiation
Saját szövet, tumor cell
Macrophage
DC
Th1
IL-2
IFNγ
TNF-β
TNF-α
GM-CSF
IL-3
IL-10
Th0
IL-10
Th2
IL-4
IL-5
IL-10
IL-13
TOLERANCE
The three types of effector T cell produce
distinct sets of effector molecules
Cytotoxic T cells alignment and delivery of
cytotoxins onto a target cell
Naïve CD8+ T cell
Microtubules (green)
Lytic granules (red)
Activated CD8+ cytotoxic T cell,
polarization and alignment of lytic
granules + cytoplasmic
components towards the target cell
Release of the clustered granules
at the site of cell-cell contact
TCR signaling
B cell activation
Phases of B cell response
Lymph node
Germinal center
(site of intense B cell proliferation)
Secondary lymphoid follicle
5. Medullary cords
(Macrophage &
plasma cell area)
Primary Lymphoid follicle
B cell zone
Paracortex
(T cell zone)
Afferent lymphatic vessel
(Lymph, Ag & cells with
captured Ag drained from
tissue enters here)
Artery
Vein
6. Efferent lymphatic vessel
Marginal sinus
(phagocytes)
Afferent lymph
Secondary
follicle (Ag)
Primary follicle
(no Ag)
B CELLS
B CELLS
Germinal
center (GC)
medulla
High endothelial
venule (HEV)
Collagen capsule
Efferent lymph
mature,naive
Mature,naive
BB-sejt
cell
FDC
T CELLS
vein
arthery
B CELLS
T CELLS
Memory B cell
Plasma cell
STRUCTURE OF LYMPH NODES
The germinal center
Where somatic Hypermutation
takes place
LZ
FDC
DZ
LZ: Light zone
DZ: Dark zone
FDC: Follicular dendritic cell
Somatic hypermutation
High frequency mutation in the rearranged heavy and light chains V domain genes (at the
CDR loops) of immunoglobulin genes in activated B cells. An almost random introduction
of single-nucleotide substitutions (point mutations) that results in variant antibodies, some
of which have higher affinity for the antigen.
1,000,000 times the ordinary mutation rate of a gene
Affinity maturation
Increasing the affinity of antigen binding sites of antibodies;
1. Somatic hypermutation and
2. The selection of the B cells with the higher affinity to the antigen to be differentiated
into plasma cell.
!!! Do not confuse with somatic recombination!!! That is DNA recombination in
immunoglobulins and TCRs gene segments during B and T cell development, that encode
the variable region polypeptide chain!
BCR signaling