W9L14-15 - B and T Lymphocytes Flashcards
Where do T and B cells come from and where are they primed by antigen?
Mature naive B cells derived from bone marrow
- primed by antigen in spleen, lymph nodes and mucosal lymphoid tissue
Mature naive T cells derived from thymus
- primed by antigen in spleen, and mucosal and cutaneous lymphoid tissue
- needs two of these signals for full activation
Microbial Antigen Delivery to Lymphoid Organs
Lymph Node
- free antigen transported in lymph fluid
- captured by follicular dendritic cells (B cell specific presenters) in node
- follicular DC not the same as DC
- FDCs derived from embryonic tissue
Spleen
- free antigen transported to spleen in blood
- captured by APCs in the spleen
- dendritic cells (T cell presenters) and macrophages
B cells
Can interact with antigen directly or by APCs
Can react with conformational proteins, sequential peptides, lipids and polysaccharides
Respond best to proteins
Can also respond to DNA in conjunction with DNA associated proteins and lipids
IR is less if not stimulated by helper T cells
IgM and IgD function as an antigen specific B cell receptors for B cell activation by antigen
Plasma cells and memory cells have the potential to survive for years in the bone marrow
CD Markers
CD - cluster of differentiation
- cluster of surface antigens on cells with which antibodies react that are used to characterise various cell types
Lab requests for immunophenotyping
- analysis of blood, bone marrow, lymph node tissue by flow cytometry
- most common test is analysis of patients peripheral blood lymphocyte populations
Markers:
CD3 - common T cell
CD4 - present on T helper cells
CD8 - present on cytotoxic T cells
CD19 - present on B cells
CD16 and CD56 - present on NK cells
T cell Maturation in the Thymus
All T cells start as double negative T cells
- CD4-CD8-TCR-
Positive selection
- all T cells become double positive (CD4+CD8+TCR+)
- selection occurs in thymic cortex
- T cells that bind to MHC molecules selected
- no MHC recognition results in apoptosis
- differentiated into CD8+ and CD4+ based on recognition of MHC class 1 or 2
Clonal Deletion
- medullary thymic epithelial cells and dendritic cells in the thymus display self antigens
- T cells expressing receptors for self antigens are bound and destroyed by apoptosis
T Regulatory Cells
- maintain tolerance to self antigens in peripheral tissues
- help to prevent autoimmune disease
Classic Role of B and T Lymphocytes
B cells (CD19+) - humoral immunity - immunoglobulin production - Ig effector functions T cells (CD3+) - T helper cells (CD3+CD4+) - activate macrophages containing antigen - stimulate killing of phagocytosed antigens T cytotoxic cells (CD3+CD8+) - bind to and kill infected target cells - virally infected cells
MHC Class 1 and 2 locations
MHC Class 1 - expressed on nucleated cells MHC Class 2 - expressed on dendritic cells - monocytes - macrophages - B lymphocytes - endothelial cells - thymic epithelium
What is the other function of CD4 and CD8?
Holds the synapse together
B cells vs T cells - Antigen Recognitions
Antigen interaction B cell - BCR binds Ag T cell - TCR binds antigenic peptides bound to MHC Nature of antigens B cell - protein, polysaccharide, lipid, peptide T cell - peptide Binding soluble antigens B cell - yes T cell - no Epitopes recognised B cell - accessible, sequential, nonsequential T cell - internal linear peptides
T Dependent Humoral Immunity
The presentation of protein/peptide antigen by B cells to primed T helper cells in the spleen and/or lymphoid tissue
- produces long living plasma cells (years) and memory B cells in the BM
- primarily IgG, IgA, IgE
In the absence of Th1 and Th2 helper T cells, B cells differentiate into short lived plasma cells
- short lived (3-5 days)
- primarily produce IgM
Antigen and T Helper Cells
Naive T helper cells stimulated by peptide antigens presented on MHC class 2 receptors by APCs 3 main types of T helper cell can be produced (Th1, Th2, Th17) These then produce cytokines which activate macrophages, inflammation and T and B lymphocytes
Function of Th1 Cells (CD4+)
Effector functions mediated by CD40 ligand on Th1 cell binding to CD40 on target cells
IFNγ is the signature cytokine involved
It enhances macrophages and APC killing of ingested microbes
B cells stimulated to produce IgG1 and IgG3
- CD40 binding stimulates B cell proliferation, differentiation and increased synthesis of immunoglobulin
- CD40 binding stimulates production of the enzyme required for isotope switching
Activation of cytotoxic T cells
Cytotoxic T cells
Kills cells infected with viruses and intracellular pathogen
Release of cytoplasmic granules
Function of Th2 Cells
Alternative macrophage activation
- tissue remodeling and fibrosis with chronic parasitism and allergic disease
- tissue repair following injury
- IL4 and IL13
Intestinal mucous secretion and peristalsis
- contribute to elimination of microbes at epithelial surfaces
- IL4 and IL13
Isotype switching of B cells to produce IgG4, IgE, IgA
- mediated by IL4
- antigen specific IgE attaches to mast cells
- mast cells degranulate upon contact with original antigen
- eosinophils degranulate upon contact with IgE coated helminths
- IgG4 can bind to Fc receptors of phagocytes and can cross placenta
Function of Th17 Cells
Release of IL17 and IL22
IL17
- pro-inflammatory recruitment of -
- neutrophils
- monocytes
IL22
- helps to maintain epithelial integrity
Th17
- effective against certain extracellular bacteria
- fungal infections
- mediates pathological response in autoimmune disease
