HRR: effector mechanisms of T cell immunity Flashcards
List the 5 types of effector T cells involved in eliminating microbes
CD8+ : cytotoxic T cells
CD4+ : Th1, Th2, Th17, Tfh helper
What are the differences between CD8+ cytotoxic T cells and CD4+ helper T cells?
CD8+ directly kill infected cells, while CD4+ helper T cells express molecules to recruit and activate leukocytes to phagocytize and destroy microbes and help them make antibodies
Describe the mechanisms by which CD8+ effector T-cells eliminate microbe
infected cells
They kill infected host cells in an antigen specific manner. They encounter a target cell containing some MHC I in common with the CTL. An immunological synapse forms via perforin, allowing the T cell to release granules from an endosome that are taken up by the target and will induce apoptosis. The CTL then detaches and can go on to repeat this process
What are the 4 effector molecules made by CTL (CD8+ T Cells)
Perforin, granzymes, fas-ligand, IFN-gamma
Describe perforins: what makes them, what they do, and what they’re homologous to
An effector made by Cd8+ T cells that can perturb cell membranes. It is homologous to complement factor 9
Describe granzymes
An effector made by CD8+ T cells. They are serine preoteases that initiate apoptosis by cleaving caspases
Describe Fas-ligand
An effector made by CD8+ T cells. They bind Fas on target cell membranes, which activate caspases and initiates apoptosis
Describe IFN-gamma in CD8+ T cells
An effector made by CD8+ T cells that activate macrophages, increase microbicidal molecules in phagolysosomes, and make IL-2
List the essential signals for a naïve T-cell to differentiate into a cytotoxic T-cell.
1.Recognition of antigen in context of MHC I
2.Positive co-stimulation by B7-1/B7-2
Describe the steps involved in differentiating a naïve CD4+ T cell into a Th effector cell
1.Innate immune system detects PAMPs and DAMPs and makes specific cytokine(s)
2.Dendritic cell presents antigen on MHC II with co-stimulation in the presence of the innate cytokine
3.Naïve CD4+ T cells differentiate to a Th effector cell, and make the same cytokine
how do we distinguish helper T cells
by the cytokines they produce
Th1: target, defining cytokine(s), function
Target: macrophages
Defining cytokine(s): IFN- gamma
Function: activate macrophages
how does Th1 activate macrophage
Via expression of CD40L and secretion of IFN-gamma. This causes the macrophage to release ROS, NO, and various cytokines to kill phagocytosed microbes.
List the signals that cause a naïve T-cell to differentiate into a Th1 effector T-cell.
IL-12 produced by a dendritic cell and IFN-gamma produced by NK cell. They form a positive feedback loop, as Th1 produces more IFN-gamma. This means more Th1 effector cells will continue to be formed
What is the unique transcription factor for differentiation into Th1?
TBET along with STAT4, STAT1
What kind of host does Th1 protect against?
intracellular pahtogens
Th2: target, major immune reaction, role in disease
Target: eosinophil
Major immune reaction: mast cell and eosinophil activation as an alternative to macrophage
Role in disease: allergy
What kind of host does Th2 protect against?
helminths
What are the defining cytokines of Th2
IL-4, IL-5, IL-13
Describe mechanisms by which CD4+ Th2 effector cells eliminate microbes.
-The secretion of IL4 induced IgE and IgG4 antibodies
-IgE bound to parasite is recognized by receptors on eosinophils and basophils, causing degranulation
-IL5 activates eosinophils
-IL4, IL13 and IL10 induce alternative macrophage
List the signals that cause a naïve T-cell to differentiate into a Th2 effector T-cell.
IL4
What is the unique transcription factor for Th2
GATA3
Th17: target, major immune reaction, role in disease
-Target: neutrophils
-Major immune reaction: neutrophil recruitment and activation
-Role in disease: autoimmunity and inflammation
What kind of host does Th17 protect against?
Extracellular bacteria and fungi
What are the defining cytokines of Th17?
IL-22 and IL-17
what is the unique cytokine in differentiation of Th17? what produces it?
IL-23; APC’s
Describe mechanisms by which CD4+ Th17 effector cells eliminate microbes.
IL-17: induces production of chemokines that recruit monocytes and neutrophils that destroy bacteria and fungi
IL-22: induces defensin production to help maintain epithelial barrier integrity
What is the unique transcription factor for Th17?
ROR-yt
Tfh cells: target, defining cytokines, major reactions
target: B cells
cytokines: IL-21 and IFN-gamma or IL-4
reaction: antibody production
what are the 3 CMI (cell-mediated immunity) evasion strategies?
Prevent phagosome killing, inhibit antigen presentation, and interference with cytokine signaling
A __ inhibitor is being used to treat eczema
IL-4
A __ inhibitor is currently being used to treat plaque psoriasis, Crohn’s disease
IL-23
Which two Th responses antagonize each other?
Th1 and Th2
Which Th response activates complement and inflammation?
Th1
Which Th response is associated with would healing and scar tissue?
Th2
Which Th response is associated with tuberculoid leprosy?
Th1
Which Th response is associated with leptromatous leptrosy?
Th2
Describe skin testing as a method for measuring CMI
Epidermal injection of antigen, and measure induration at 48-72 hours. Greater than 5 mm indicates a positive response. This measures Th1 specifically.
What is diapedesis
T cells exiting the blood vessel wall and entering the tissue. If they’re activated they stay in the tissue, and if they’re not they’ll return to circulation
Describe flow cytometry as a method for measuring CMI
Allows for cell identification, counting, and sorting. Cells are incubated with fluorescent tagged antibodies for specific CD markers. Individual cells are counted, and their degree of fluorescence is measured.
Describe cell proliferations assays
Lymphocytes are stimulated by radioactive nucleotides. The dividing cells incorporate the radioactivity, and the radioactivity of divided cells can then be quantified and compared to unstimulated cells. This can look for specific antigens, polyclonal activators, or microbial superantigens
what does flow cytometry measure
differentiate between lymphocytes using fluorescent antibodies
what do cell proliferation assays measure
thymidine is used to measure proliferation of T cells; lets us look at the functioning of signal transduction pathways/T cell activation
