The Adaptive Immune Response

Jeffrey TsoKaren Ka Yan Ng

Kaitai YeMarina Simeonova PHM142 Fall 2014

Instructor: Dr. Jeffrey Henderson

Time course of the Adaptive Immune Response

Janeway’s Immunobiology, 2012

Antigen Processing, Prep and Presentation

Janeway’s Immunobiology, 2012

Dendritic Cell Path

Stimulation of T cells by Dendritic Cells

Janeway’s Immunobiology, 2012

Stimulation of T cells by Dendritic Cells

Janeway’s Immunobiology, 2012

T Cell Proliferation and Differentiation

Janeway’s Immunobiology, 2012

• Activated T cells become effector T cells, and differentiate to fill various roles. The role depends on the type of interleukins that the cells are exposed to.

• Types of T cells include:

Effector T cell Differentiation

Janeway’s Immunobiology, 2012

Cytotoxic T cells

Janeway’s Immunobiology, 2012

T Helper Cells

Janeway’s Immunobiology, 2012

T Helper Cells

Janeway’s Immunobiology, 2012

• Help regulate the immune response• Suppress activation of immune system when

no infection present• Down-regulated in times of infection• Deficiencies in regulatory T cells can lead to

autoimmune diseases

T Regulatory Cells (Tregs)

• Naïve B Cell recognize free (soluble) antigen using their BCR or membrane bound-immunoglobulin.

• Rapid response, no isotype switching, no affinity maturation

T Cell Independent B Cell Activation

• For Thymus Dependent (TD) Antigens

• Antigen-MHC Signal- B Cell Antigen MHC 2 – T Cell Receptor (TCR)

• T Cell induced to express CD40 Ligand, CD30 Ligand- B Cell CD40, CD30

• T Cell secretes cytokines ie. IL4,5,6 and B Lymphocyte stimulator (BLyS)

• Slower response, isotype switching, and affinity maturation

T Cell Dependent Linked Recognition

Janeway’s Immunobiology, 2012

Janeway’s Immunobiology, 2012

Isotype Switching

Janeway’s Immunobiology 2012

• Antibodies as know as immunoglobulins are molecules ranging from 146-188kDa and 980kDa for IgM.

• Important to form tailored antibodies to the infection• Vh , Vl, C domain• Naive B Cells express primarily IgM and IgD, but serum levels

of IgM are less than 10%, with IgG being the most abundant• Th Cell CD40 Ligand, IL4, TFG-Beta, INFy- alternate splicing

of Ig mRNA• Light chain variable for every pathogen depending on the

presented antigen

Isotype Switching

• Opsonize Pathogens (IgGs)• Neutralize Toxins (IgG and IgA)• High affinity Ig’s may limit viral infectivity (IgA and IgG vs hemagglutinin in

influenza)• Activate complement

Purpose of Antibodies

TYPES OF ACTIVATED B CELLS

PLASMA B CELLSMEMORY B CELLS

B-1 CELLSB-2 CELLS

Marginal Zone B cellsRegulatory B cells

• Also known as Plasma cells, plasmocytes, effector B cells

• Large B cells that have been exposed to antigen secrete large amounts of antibodies

• Assists in the destruction of microbes easier target for phagocyte + activation of complement system

Plasma B cells

• Sometimes referred to as antibody factories• Large amounts of Rough ER (to synthesize the

antibody)• Short lived, undergo apoptosis when the

inciting agent that induced immune response is eliminated.

Plasma B cells

• Differentiate from activated B cells predominately from a germinal center.

• Specific to the antigen encountered during the primary immune response

• Able to live for very long time• Can respond quickly following a second

exposure to the same antigen

Memory B cells

• Express IgM in greater quantities than IgG• Low in numbers in the lymph nodes and

spleen and are instead found predominantly in the peritoneal and pleural cavity

B-1 Cells

• Cells intended when using the unqualified “B cell”

• Majority in the spleen and lymph• Cells are small, long lived resting cells that

express low levels of surface IgM and high amounts of IgD

• Unlike B-1 cells, these cells do not express CD4 antigen found on all T cells

B-2 Cells

• B cells involved in immune regulation via various mechanism

• Also known as Breg cells• Positive regulators of immune because of capability to

produce antibodies, including antibodies• Production of antibodies facilitate optimal CD4+ T-cell • Also negatively regulate the immune response by

producing regulatory cytokines and directly interacting with pathogenic T cells via cell-to-cell contact

Regulatory B Cells

Summary slide

3 signals are needed in order for an Antigen Presenting Cells (APCs) to stimulate a naïve T cells: 1. Antigen Specific Signal: MHC Class II + TCR2. Co-stimulatory Signal: B7 + CD283. Differentiation Signal: APC secretes a variety of cytokines promoting different effector T cell outcomes An absence of the antigen-specific signal will lead to anergic or clonally deleted T cells Types of Effector T-CellsCytotoxic T cells (Tc/CD8): kills infected cellsHelper T cells (Th/CD4): Th1, Th2, Th17- activates other immune cells ie. Naïve B CellsTreg: regulates immune response B CellsNaïve B cells are activated via T Cell independent or dependent route. Independent: pathogen phagocytosis using BCR, non-isotype switching antibody productionDependent: linked recognition: phagocytosis; display on MHC Class 2, interact with Th Cell which presents (CD40) Ligand and B Lymphoctyte stimulator (BLyS) Activated B CellsPlasma Cells: migrate to cite of infection and secrete antibodiesMemory B Cells- assist in future response to the same antigenRegulatory B Cells- Secrete cytokines to regulate immune responses Antibody Isotype Switching2 variable regions, light(VL) and heavy(VH) Primarily IgM, highest levels in serum IgG. Th Cell CD40L is necessary for Ig splicing and isotype switching to occurAntibodies can: opsonize pathogens, neutralize toxins, limit viral infectivity, activate complement pathway

References• Janeway et al. (2001), Immunobiology: Garland Publishing, New York• Neuberger, M. S.; Honjo, T.; Alt, Frederick W. (2004). Molecular biology of B cells.

Amsterdam: Elsevier. pp. 189–191. ISBN 0-12-053641-2.• Lang ML (Aug 2009). "How do natural killer T cells help B cells?". Expert Rev Vaccines 8

(8): 1109–21. doi:10.1586/erv.09.56. PMC 2747240.PMID 19627191.• Martin F, Kearney JF. Marginal-zone B cells. Nat Rev Immunol. 2002;2(5):323–335.• Neuberger, M. S.; Honjo, T.; Alt, Frederick W. (2004). Molecular biology of B cells.

Amsterdam: Elsevier. pp. 189–191. ISBN 0-12-053641-2.• Lang ML (Aug 2009). "How do natural killer T cells help B cells?". Expert Rev Vaccines 8

(8): 1109–21. doi:10.1586/erv.09.56. PMC 2747240.PMID 19627191.• Martin F, Kearney JF. Marginal-zone B cells. Nat Rev Immunol. 2002;2(5):323–335.