The Adaptive Immune Response Jeffrey Tso Karen Ka Yan Ng Kaitai Ye Marina 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

Isotype Switching Janeway’s Immunobiology 2012

Antibodies as know as immunoglobulins are molecules ranging from kDa and 980kDa for IgM. Important to form tailored antibodies to the infection V h, V l, 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 CELLS MEMORY B CELLS B-1 CELLS B-2 CELLS Marginal Zone B cells Regulatory 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 + TCR 2. Co-stimulatory Signal: B7 + CD28 3. 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-Cells Cytotoxic T cells (Tc/CD8): kills infected cells Helper T cells (Th/CD4): Th1, Th2, Th17- activates other immune cells ie. Naïve B Cells Treg: regulates immune response B Cells Naïve B cells are activated via T Cell independent or dependent route. Independent: pathogen phagocytosis using BCR, non-isotype switching antibody production Dependent: linked recognition: phagocytosis; display on MHC Class 2, interact with Th Cell which presents (CD40) Ligand and B Lymphoctyte stimulator (BLyS) Activated B Cells Plasma Cells: migrate to cite of infection and secrete antibodies Memory B Cells- assist in future response to the same antigen Regulatory B Cells- Secrete cytokines to regulate immune responses Antibody Isotype Switching 2 variable regions, light(V L ) and heavy(V H ) Primarily IgM, highest levels in serum IgG. Th Cell CD40L is necessary for Ig splicing and isotype switching to occur Antibodies 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 Lang ML (Aug 2009). "How do natural killer T cells help B cells?". Expert Rev Vaccines 8 (8): 1109–21. doi: /erv PMC PMID 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 Lang ML (Aug 2009). "How do natural killer T cells help B cells?". Expert Rev Vaccines 8 (8): 1109–21. doi: /erv PMC PMID Martin F, Kearney JF. Marginal-zone B cells. Nat Rev Immunol. 2002;2(5):323–335.