Cell-Mediated Immunity: T Cells

TH2 cells are characterized by the secretion of?

Cytokines IL-4 and IL-5.

What does IL-5 do?

Elicits B cell growth, activates eosinophils, and enhances IgE production.

Naive T cells recirculate from the lymph nodes to the blood, facilitating what?

Encounter with antigen

True or false: Memory cells can only be CD4+.

False. Memory cells may be either CD4+ or CD8+.

How are T cells and B cells distinguished?

Flow cytometry-look for surface antigens CD (cluster of differentiation)

Aberrantly low level of CD4+ T cells represents?

HIV Disease/AIDS

What are thymocytes?

Hematopoietic progenitor cells originate from bone marrow and lack expression of T cell receptor.

TH1 cell differentiation requires?

IL-12 and IFN gamma, secreted by activated macrophages, dendritic cells, NK cells.

What do TH16 cells secrete?

IL-17 and IL-22, which stimulate inflammation and contribute to protection against bacterial and fungal infections.

CD4+ T cells respond to?

MHC II

What are the phenotypic markers of B cells?

MHC II, pan-markers of CD19, CD20, CD21, CD22, CD23, marker of activated B cell CD57

Bacterial toxin activation of T cells can lead to?

Massive T cell responses, which are the basis of toxic shock syndrome, food poisoning, etc.

IL-2 functions in what manner?

Autocrine; cytokine is secreted and bound by activated T cells.

An aberrantly high level of T cell activation is associated with?

Autoimmune diseases (systemic lupus, erythematosus)

How many signals are required to activate T cells?

2 signals (co-stimulation)

What are CD8+ T-lymphocytes?

35% of peripheral blood T cells. Cytotoxic T-lymphocytes (Tc or CTLs) release cytolytic substances such as perforin, granzyme, and ligands directly into target cells,w which promotes apoptotic-cell death. Associated with MHC I. The primary role of CD8+ T cells is to destroy virally-infected cells and tumor cells and implicated in transplant rejection.

What do CD4+ T-lymphocytes do?

65% of peripheral blood T cells. T-helper lympohcytes, effector T cells, TH cells. Help and induce activation of B-lymphocytes and other cells by secreting cytokines. These are the "middlemen" of adaptive immune system. Depending on cytokine signals received, they differentiate into different subclasses of TH cells, which secrete specific cytokines unique to each sub-class of TH cells.

What is clonal expansion?

A large number of antigen-specific T cells are generated.

MHC I are found on?

All nucleated cells in the body

TH2 cells promote?

B cell expansion and plasma cell differentiation.

Where does the induction phase of cell-mediated immunity take place?

Lymphoid organs (lymph node)

CD8+ T cells respond to?

MHC I

What do TH17 cells secrete?

Pro-inflammatory cytokine IL-17.

Where does T-lymphocyte differentiation occur?

Thymus

What are Regulatory cells (Treg)

Act as brake on T-lympohcytes. Shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection.

Upon recognition by the TCR of the appropriate peptide:MHC complex found on the surface of an antigen presenting cell, the naive T cell (CD4+ or CD8+) is __?

Activated, proliferates, and differentiates into a CD4+ helper effector or CD8+ cytotoxic effector T cell. Otherwise, it dies within 5-7 weeks.

What is the effector function of CD4+ helper T cell in humoral immunity?

Activates antigen-specific B lymphocyte to secrete antibodies with enhanced abilities to neutralize and eliminate antigens.

What does a TH1 cell do?

Activates macrophages (to ingest extracellular bacteria and viruses and increases ability of macrophages to kill ingested intracellular pathogens) and IgG production. Associated with autoimmune disease, tissue damage associated with chronic infections. Signature cytokine: IFNgamma.

What is the effector function for CD4+ helper T cells in cell-mediated immunity?

Activates macrophages for the killing of phagocytosed microbes

What is the principal action of IL-5?

Activation of eosinophils.

What does Interferon-gamma (IFN-gamma) do?

Activation of macrophages.

What does a TH2 cell do?

Activation of mast cells, eosinophils; IgE production; "alternative" macrophage activation. Defense against helminthic parasites. Role in allergic diseases. Signature cytokines: IL-4, IL-5, IL-13.

What is the CD8+ cytotoxic T cell effector mechanism?

Antigen recognition and binding of CTL to target cell, CTL activation and granule exocytosis, apoptosis of target cell. Perforin facilitates granzymes entry into the cytosol. Granzymes activate apoptosis.

What is the principal action of IL-4?

B cell switching to IgE.

What does IL-2 do?

Binds to the high affinity receptor CD25 that is upregulated by activated T cells, and in turn promotes cell division. A large number of antigen-specific T cells are then generated.

What are the cellular sources of TGF-beta?

CD4+ T cells and many others.

What are the cellular sources of IL-17?

CD4+ T cells and others.

What are the cellular sources of IL-4?

CD4+ T cells, mast cells.

What are the cellular sources of IL-5?

CD4+ T cells, mast cells.

What are the cellular sources of IFN-gamma?

CD4+ and CD8+ T cells, natural killer cells.

What are the sources of IL-2?

CD4+ and CD8+ T cells.

How do CD4+ T cells help CD8+ T?

CD4+ helper T cells produce cytokines that stimulate cytotoxic T cell (CTL) differentiation and enhance the ability of antigen-presenting cells to stimulate CTL differentiation.

MHC II are found on?

Dendritic cells, macrophages, B lymphocytes, endothelial cells, thymic epithelium.

What does IL-4 block?

Differentiation of TH1 cells.

What is positive selection in thymic education?

Double positive thymocytes with TCR that bind MHC I OR MHCII with LOW to MODERATE affinity receive signals for further development. Essentially start with double positive, then in the thymus, select CD4 or CD8

What is the primary function of T cytotoxic cells?

Lysis of virally infected cells and tumor cells.

T cell proliferation is dependent on what cytokine?

IL-2. T cells undergo a burst of proliferation that is dependent on IL-2.

Differentiation of TH2 cells is dependent on?

IL-4. Basophils are thought to be an early source of IL-4.

What is required for the differentiation of TH17?

IL-6 and TGFbeta.

What does TGF-beta do?

Inhibition of T cell activation, differentiation of regulatory T cells.

TCR alpha and beta chain loci each contain?

Multiple V(ariable) region genes, one/few C(constant) region genes,b between these are stretches of J(joining) and D(diversity) genes.

When happens when T cells recognize an antigen?

Naive T cells is activated, undergoes clonal expansion, and differentiation.

Single-positive cells leaving the thymus are called what?

Naive T cells. They leave in a "resting" (unactivated) phenotype.

What does a TH17 cells do?

Neutrophilic, monocytic inflammation. Defense against extracellular bacteria and fungi. Role in organ-specific autoimmunity. Signature cytokines: IL-17A, IL-17F, IL-22.

What are the phenotypic markers of T helper cells?

Pan-marker for TCR alpha beta, CD3, CD4 (specific), activated T cell CD38.

What are the phenotypic markers for T cytotoxic cells?

Pan-marker for TCR alpha beta, CD3, CD8 (specific), highly specific for CRTAM.

TCRs recognize?

Peptide epitopes derived from processed antigens that are bound in the context of self-MHC molecules.

TH1 cells are characterized by the secretion of?

Pro-inflammatory cytokines IFNgamma and TNFalpha.

What does IL-4 do?

Promotes B cell proliferation, enhances IgE class switching, and recruits eosinophils, blocks differentiation of TH1 cells.

What is the primary function of T helper cells?

Release cytokines and growth factors that regulate other immune cells.

Antigen-dependent proliferation of T-lymphocytes occurs in?

Secondary lymphoid organs: spleen, lymph nodes, MALT

What is the primary function of B cells?

Secretion of antibodies

What are the two signals required to activate T cells?

Signal 1: TCR binding a peptide:MHC complex. Signal 2: CD28, expressed by naive T cells, binds to B7-1/B7-2

The initiation and the expression of IL-2 requires?

Signals delivered by TCR:MHC co-receptor complex and CD28.

What kind of thymocytes leave the thymus?

Single-positve thymocytes.

The binding of TCR and MHC provides?

Specificity.

What are the stages of T-lymphocyte maturation?

Stem cell, pro-T, pre-T, double positive, single positive immature T cell, naive mature T cell

What does IFNgamma do?

Stimulates macrophages ot ingest extracellular bacteria and viruses, induces IgG2a and IgG3 class switching by B cells, which promote opsonization of microbes, blocks differentiation of TH2 cells to ensure progression of cell-mediated immune response.

What does IL-17 do?

Stimulation of acute inflammation.

What are memory T cells?

Subset of antigen-specific T cells that persist long-term after an infection has resolved. Can be memory cells for decades. Quickly expand to large numbers of effector T cells upon exposure to their cognate antigen, thus providing immune system with "memory" against past infections. Can be either CD4+ or CD8+.

What is the principal action of IL-2?

Survival, proliferation, and differentiation of effector and regulatory T cells.

The success of organ transplant requires?

T cell activation suppression

Immunosuppression relies heavily on blocking?

T cell activation.

What happens in the absence of co-stimulatory signal 2 (CD-28)?

T cell becomes energized and is no longer responsive to antigen stimulation. Anergy is a mechanism of self-tolerance induction.

What are immunoreceptor tyrosine-based activation motifs (ITAMs)?

These are phosphorylated by cytoplasmic protein tyrosine kinases that are activated once TCR clustering occurs following peptide:MHC binding.

What are double-negative thymocytes?

These early thymocytes do not express CD4 or CD8 (double negative thymocytes). Double negative thymocytes up-regulate expression of the cell surface glycoproteins followed by TCR gene arrangement.

What are CD3 proteins?

They are closely associated with the TCR, and have cytoplasmic tails that contain sequences called immunoreceptor tyrosine-based activation motifs (ITAMs).

What enzyme mediates DNA recombination and RNA splicing leading to the recombination of one V gene with one D and one J segment, which is then spliced onto one C region RNA?

VDJ recombinase

What is negative selection in thymic education?

alpha:beta double positive thymocytes that bind self-peptide or MHC I or MHC II with high affinity are deleted.