T Cell Immunity Flashcards
Define recent thymic emigrant (RTE) cells.
- naive T lymphocytes that egress from the thymus
- must go to secondary lymphoid organs and peripheral tissue to mature
- if activated before first pass, will behave inappropriately; most likely differentiate into Treg
Define adaptive immune response.
- initiated when naive T cells encounter their antigen on MHC of APCs
- TCR signaling => T cell activation
- effector T cells are generated
- act on target cells, not the pathogen itself
Differentiate between naive and memory T cells.
- expression: naive (CD45RA); memory (CD45RO)
- memory cells live longer
Differentiate between effector and central memory T cells.
- effector memory T cells: rapidly mature into effector cells upon reactivation => go to inflamed tissue; no CCR7
- central memory T cells: take longer to produce cytokines; remain in lymphoid tissue and circulate as naive T cells; CCR7
What signals are required for a successful T cell activation?
- activation: TCR recognizes peptide:MHC
- survival: costimulatory molecules (CD80/86, CD40L/40)
- differentiation: cytokine expression and secretion - dictates different T cell responses and fates
- activated T cells express the trimer of alpha, gamma, and beta chains to produce a high affinity IL-2 receptor (IL2Ra), also called CD25 (naive T cells only have gamma and beta; moderate affinity)
Describe the function and target pathogens of CD8 T cells.
Function - kill virus infected cells
Pathogens - viral; some intracellular bacteria
Describe the function and target pathogens of CD4 Th1 cells.
Function - activate infected macrophages; help B cells to produce antibodies
Pathogens - intracellular pathogens, microbes, extracellular bacteria
Describe the function and target pathogens of CD4 Th2 cells.
Function - provide help to B cells for antibody production; switching to IgE
Pathogens - soluble antigen, bacteria, helminth parasites, extracellular pathogens
Describe the function and target pathogens of CD4 Th17 cells.
Function - enhance neutrophil response; promote barrier integrity (skin, intestines)
Pathogens - fungi (candida), klebsiella, extracellular bacteria, eukaryotic pathogens
Describe the function and target pathogens of Tfh cells.
Function - help B cells in isotype switching and antibody production
Pathogens - all types
Describe the function of Tregs.
suppress T cell responses
List the following in reference to Th1 cells:
- inducer cytokines
- transcription factor
- signature cytokines
- inducer cytokines = IL12*, IL18, IFNg
- transcription factor = Tbet
- signature cytokines = IL2, IFNg, Lta
What disorders are impaired Th1 cell function associated with?
autoimmune disorders (diabetes)
What disorders are impaired Th2 cell function associated with?
immunopathology of asthma, allergies, dermatitis
What kind of immunity are Th17 cells involved with?
gut immunity
What is the immune response of Thf cells?
proliferation of B cells, differentiation of B cells into memory cells
What is the effect of TLR signaling?
cytokine expression
Where are TLRs found?
on surface membrane or intracellular membranes
What do TLRs respond to?
Different sections of pathogen molecules (ex: diacyl lipopeptides, triacyl lipopeptides, flagellum, LPS)
What is unique about TLR1, 6, and 10?
- ancient; inherited from neanderthal
What are TLR ligands called?
- PAMPs (pathogen)
- DAMPs (damage/danger)
- MAMPs (microbial)
Which T cells express TLR?
all TLRs are found on T cells (depends on if naive or mature)
Describe antigen uptake and presentation by macrophages and dendritic cells.
- pathogenic ligand binds to TLR
- phagocytosis of antigen and antigen processing
- antigen is presented on MHC molecules
What triggers the conversion of immature DC to mature? What are the characteristics of a mature DC?
trigger = antigen uptake
- decreased phagocytic capability
- upregulate MHC
- upregulate CCR7 to migrate to lymphoid
- upregulate costimulatory molecules (CD40, CD80/86)
- upregulate cytokine production of IL12 and Il18
Describe what happens when a mature DC meets its T cell in the lymph nodes.
- CCR7 expressing DC enters via afferent lymphatics and travels down the cortical sinus toward the paracortex where T cells reside
- T cells that do not find their antigen leave the lymph nodes via HEV
- T cells that find their antigen bind to DCs and differentiate
- differentiated T cells leave and migrate to the infected tissue
What immune response processes are Th1 cells involved with?
- cell mediated inflammation
- hypersensitivity delayed-type
- intracellular pathogen immunity
Describe the sequential events related to Th1 differentiation.
- TLR => antigen uptake => mature APC
- mature APC activates naive CD4 T cell (TCR:MHC, CD40/40L, CD28:CD80/86)
- APC upregulates release of cytokines IL12 and IL18
- IL12 stimulates T cell to upregulate TF Tbet, upregulates IL12R (positive feedback)
- Tbet upregulates IFNg, which further stimulates production of Th1 signature cytokines (IFNg, IL2, LTa)
- IL18 works to maintain and stabilize the Th1 response
Define IFNg. What cells produce it? Function?
Interferon-gamma is a proinflammatory cytokine
- produced by Th1 (signature), NK cells, CD8 cells
- activates macrophages by stimulating antigen processing, upregulation of MHC, and TLRs
- antimicrobial
- stimulates chemokine secretion
- suppresses Th2 and Th17