Linfocitos B y T-Depurated

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5/26/2021

Biology of
Lymphocytes B & T
D R . J O R G E D. M E N D E Z R Í O S
SCH OOL OF MEDICINE
I N T E R A M E R I C A N U N I V E R S I T Y O F PA N A M A
M AY 2 0 2 1

Puntos a presentar
¿Qué son los Linfocitos?
Qué los diferencian?
Qué funciones tienen?
Qué proteínas interaccionan en la presentación de
antígenos y qué células intervienen?
Cómo ocurre la presentación y la activación?

APC
Antigen: ag
CD4+ T-cell
YY
CD8+ T-cell Cytokines
B-cell
Y

And
Y

Chemokines Y
Y
Death signals: Y Y
Perforin
Granzyme etc.

Lysis
Clearance,
Neutralization

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Diferenciación de los
Linfocitos

¿Qué son los Linfocitos B?


I. Los linfocitos B son 1) células mono nucleadas, 2) asociadas a la
respuesta inmune adquirida humoral, 3) que producen anticuerpos.
II. Representan un 25% del total de leucocitos, y 10% de los linfocitos.
III. Producidas en la médula ósea en su mayoría.
IV. Como función principal, producen anticuerpos que permiten la
inactivación de agentes foráneos y la subsecuente activación del
sistema inmune.
◦ Producen anticuerpos
◦ Secretan citoquinas.
◦ Y presentan antígenos a las células T.

https://www.akadeum.com/b-cell/

Presenting cells and Effector Cells

Presenting cells: all cells capable of


binding an antigen, processing,
recruiting other cells to activate an
Antibody- immune response.
Antigen
complex Effector cells: cells that are activated
upon the presentation of an antigen by
a presenting cell (APC), in order to
mount an immune reponse.

T cell (One of the effector cells)

B cell (one of the APC cells = presenting)

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Lymphoid linage

Mature Lymphoid cells

https://www.cusabio.com/manage/upload/201905/1559223729.jpg

B cells differentiates depending on


the microenvironment

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Maturation of B cells
Major membrane receptors:
B cells receptors (BCR)
Inmunoglobulins (secreted antibodies)
Co-receptors: CD19 and CD20)
Plasma
IgM IgM IgD IgM

Lymphoid Pro Bcell Pre Bcell Immature BCell Mature Bcell Activated Bcell Memory Cell

Antigen independent Antigen dependent


Primary Linphoid Organ Secondary Linphoid Organ

Antigen presentation through


antibody or through MHC
Celular proteins involved in presentation
IgG: they are antibodies attached to the B
lymphocytes.
(CTL)
TCR (CTL) BCR: B-cell receptor similar to antibody with
antigen transmembrane domain and complexes.
TCR
Antibody antigen TCR: T cell repector
BCR MHC II MHC I (same as HLA I): Mayor
Histocompatibility complex I
(B cells) (APCs) MHC II (same as HLA II): Mayor
Histocompatibility complex I
CD4 and CD8, KIR, ICAM-1: T Lymphocyte
(CTL) co-receptors
CR2, CD19: B lymphocyte co-receptors

B cell activation for clonal


expansion

Charles A. Janeway jr. u. a.: Immunologie. 5. Auflage. Spektrum Akademischer Verlag Gmbh, Heidelberg, Berlin 2002, ISBN 3-8274-1078-9.

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Overview: Activation and


recognition of antigens by B cells

https://i.pinimg.com/originals/26/ca/90/26ca90efa065b51d531f18514cf7b17f.png

Overview: Activación y expansión


clonal de Linfocitos B

How does B cell activation


occurs?

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Antigen receptors and coestimulants


different on each cells

B cells activation phases

Clonal amplification of B cells

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Antigen specificity

Importance and requirement


of hapten-carrier complex.

Cross-reactivity of antigens

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Origin of auto-inmune diseases


(recognition of self antigens or
cross-reactivity)

Cross-reactivity to similar
antibiotics

Presentation and activation of


effector cells can occur through
several mechanisms

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2 ways of processing and presenting antigens

Different mechanisms of
antigen presentation

(CTL) (CTL)
(CTL)
TCR TCR
antigen TCR antigen
antigen antigen
Antibody MHC II
MHC I
BCR FcR
(APCs)
(APCs)
(B cells) (B cells)

BCR-antigen FcR-antibody- MHCI-antigen-TCR-CD8 MHCII-antigen-TCR-CD4


antigen-TCR
B Lymphocytes B lymphocytes APCs MHCI + APCs MHCII +
followd by Upon activation
endocytosis

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Activation of B cells at the


molecular level

Antigen
processing

Antigen
presentation
by MHC II-containing
cell to CD4 cell
(MHC II)

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Signaling cascades

Signal transduction
in a B cell (APC)
upon antigen
recognition

Intracellular cascade after


antigen binding in B cells.

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Intracelluar and nuclear signaling


after activation of B cells

Activation of T cells at the


molecular level

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Antigen presentation by a MHC I-


containing cell to a CD8 cell

Summary of B and T cell signal transduction

Doreen Cantrell, Signaling in Lymphocyte Activation, Downloaded from http://cshperspectives.cshlp.org/ on September 24, 2018 -

Summary of events of immune


cells

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Sumary: Major checkpoints in


B Lymphocyte activation
pMHC+ DC gets activated and migrate to LN (Lymph Node): Checkpoint I
DC presents antigen to naïve Th lympocyte, activating different types of
LTh’s: checkpoint II
LTh’s through their receptors, interact with SHM (Somatic
hypermutation), and down regulating the BCR.
Abundant apoptosis occurs for most B cells expression BCR, followed by
positive selection of high-affinity BCR+ LB.
pMHCII+ memory B cell and antigen-specific memory Th cells:
Checkpoint IV

Resumen
Las células dendríticas y los Linfocitos T son esenciales para la
activación, diferenciación y expansión clonal de los Linfocitos B.
El proceso de diferenciación ocurre principalmente en el tejido linfoide
secundario.
La activación de los Linfocitos T producen diversos tipos de Linfocitos T,
y cada subtipo induce un efecto diferente en los Linfocitos B.
Múltiples subtipos de linfocitos B son producidos: de memoria, celulas
plasmáticas (de vida corta o de vida larga)
Los Linfocitos B pueden presentar antigenos tambien a través de los
BCR, anticuerpo-ligando y MHCII.

T Lymphocytes

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LTh

NK

LTh: Helpers Lymphocyte T cells CTL


CTL: Cytotoxic Lymphocytes
NK: Natural Killers

T-cell Subsets and Functions

1. Cytotoxic T cells (CTL) kill infected cells.

•Are identified by the surface marker CD8


(CD8+ T-cells)

•Control intracellular pathogens such as viruses


and bacteria

•Require cell to cell contact to bind antigen

•Bind only antigen presented on the surface of


cells

T-cell Subsets and Functions


2. Helper T cells (Th) provide “help” for
cytotoxic T cells and B cells.
• Are identified by the surface marker CD4
(CD4+ T-cells).

• Also require cell to cell contact to bind antigen.


• Bind only processed antigen
• Secrete cytokines and chemokines.

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Presenting cells and Effector Cells


MHCI o MCHII
Antigen
complex

Antibody-
Antigen
complex

T cell (One of the effector cells)

B cell (one of the APC cells = presenting)

Presentation occurs differently depending of

APC
Antigen: ag
CD4+ T-cell
YY
CD8+ T-cell Cytokines
B-cell
Y

And
Y

Chemokines Y
Y
Death signals: Y Y
Perforin
Granzyme etc.

Lysis
Clearance,
Neutralization

APC-side
peptide
presentation
(CD3,TCR)

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2 major types
of correceptor
in T lymphocytes

Recognition, clustering and activation of


effector cells (TCR)

Resumen: efectos de
estimulación de Linfocitos T

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