Flashcards in L5: T-Cells / Cell-Mediated Immunity Deck (21):
Describe ontogeny of T lymphocytes
- Prothymocytes from bone marrow migrate to thymus where they become thymocytes
- Thymocytes differentiate into mature T cells within the thymus
- Mature T cells travel from thymus to peripheral lymphoid organs
- Memory T cells reside in bloodstream until needed to elicit cell-mediated immune responses
List various forms of T cells in the body. What are their functions?
1.) T-helper cells (CD4+)
a.) TH1: participate in cell-mediated immunity (IgG)
b.) TH2: participate in humoral immunity (esp. via IgE)
c.) TH17: enhances inflammation
d.) Tfh: promote germinal center formation in lymphoid organs
2.) Cytotoxic T cells (CD8+): lyse virus-infected cells
3.) Regulatory T cells (aka Treg cells): downregulate immunity
What confers MHC restriction to the T cell?
- CD4 and CD8
- No the TCR itself
Structure of TCR
- Heterodimer of alpha and beta chains, each chain has constant and variable regions similar to antibodies
- Short cytoplasmic tails
- Only has single antigen binding site
- Never secreted
Associated transmembrane protein with TCR. Purpose?
- TCR’s cytoplasmic tails are not long enough to act as signal transducers
- It requires CD3 to transduce signal, cytoplasmic tails of CD3 are phosphorylated
In order for a T-cell response to occur, one of the signals required are from co-stimulatory molecules/interactions. What are these?
- CD28 (on T-cell) binds B7 (on APC)
- CD40L (L = ligand on T-cell) binds CD40 (on APC)
What are the 3 signals needed in order for a T-cell to become activated?
1.) Processed peptide expressed on class I or II MHC
2.) Co-stimulatory molecules (CD28:B7, CD40L:CD40)
3.) Production and liberation of cytokines that bind T cells
What is hyperIgM syndrome?
- Immune deficiency where T-cells don’t express CD40L
Describe characteristics and functions of CD4
- transmembrane glycoprotein consisting of a single polypeptide expressed on 2/3rds of T cells, most are TH cells, present in small quantities of macrophages
- function: CAM, signal transduction, restricts T cells to class II MHC
Describe characteristics and functions of CD8
- homo/heterodimer expressed on a subset of T cells
- function: CAM, signal transduction, restricts T cells to class I MHC
Discuss activation and signal transduction in T cells
1.) TCR binds to MHC-bound antigen, co-stimulatory signals and cytokine stimulation
2.) Phosphoinositide pathway, RAS, MAP kinase pathways are activated. PKC and other kinases phosphorylate transcription factors
3.) AP-1 (TF) initiates IL-2 cytokine production (autocrine)
4.) Mitosis causes expansion of antigen-specific clones to amplify an immune response 48-72 hours after stimulation through TCR
What is required for naïve T cells to develop into TH1 cells?
- TH1 cells will develop when naïve T cells receives signaling from IL-12, which is produced under conditions of inflammation caused by various bacteria, viruses and other pathogens
Action of TH1-mediated immunity on macrophages? On CTLs?
- TH1 cells cause classical macrophage activation through release of IFN-gamma, which enhances microbial killing
- TH1 cells produce cytokines that stimulate CTL differentiation. They also enhance the ability of APCs to stimulate CTL differentiation
What is required for naïve T cells to develop into TH2 cells?
- TH2 cells develop when they receive signaling from IL-4, thought to be produced by mast cells or antigen-activated T cells
Action of TH2-mediated immunity?
- TH2 cells produce IL-4, IL-13 and IL-5, which directs the immune response toward IgE production for anti-parasite defense particularly against helminth infestations
- Can also lead to alternate macrophage activation for tissue repair
What is required for naïve T cells to develop into TH17 cells?
- Exposure to IL-1, IL-6 (produced by DCs during anti-microbial defense) and TGF-beta (from various cell types)
Action of TH17-mediated immunity?
- Secrete IL-17 and IL-22, which promote inflammation: antimicrobial peptides, increased barrier function, neutrophil response
Describe how TH1 and TH2 responses are regulated
- TH1 and TH2 cytokines have antagonistic responses
- IFN-gamma produced in TH1 response, inhibits TH2 responses
- IL-4 and IL-13 produced in TH2 response, inhibits TH1 response
How are CTLs activated?
- By TH1 cells that produce cytokines that stimulate CTL differentiation. TH1 cells also enhance the ability of APCs to stimulate CTL differentiation.
Function of CTLs?
- destroy intracellular microbes (viruses, some bacteria), tumor cells and transplanted tissues and organs