Lymphocytes
What are the effector functions of TH1 cells?
1) Activate macrophages to increase phagocytosis and killing of pathogens (makes macrophages enter to activated state) 2) Produce IL-2, IFN-gamma and TNF-B 3) Stimulate CD8+ Tcells (i.e. a cell-mediated response) 4) Stimulate isotype switching in B cells from IgM to IgG2 & IgG3, and IgA *FOR INTRACELLULAR PATHOGENS*
What are the functions of NK cells?
1) Direct killing of target cells by releasing cytotoxic enzymes from granules 2) Production of IFN-gamma
What are the effector functions of TH2 cells?
1) Produce IL-4, IL-5, IL-6, IL-10 2) Stimulate B cells to produce antibodies (i.e. humoral response) 3) Stimulate isotype switching from IgM to IgG1, IgE and IgA *FOR EXTRACELLULAR PATHOGENS*
Lymphocytes make up what percentage of WBCs? Lymphocytes make up what percentage of cells in the lymph? How many lymphocytes are in circulation in a normal adult?
20-40% 99% 1 trillion
What are lymphocytes?
A lymphocyte is any of three subtypes of white blood cell. All three are agranulocytes. They include natural killer cells (NK cells) (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adaptive immunity), and B cells (for humoral, antibody-driven adaptive immunity). They are the main type of cell found in lymph, which prompted the name lymphocyte.
What is cell-mediated immunity?
A type of acquired immunity in which T lymphocytes, along with CD4 Helper cells and CD8 Killer cells, target INTRAcellular pathogens.
What are B lymphocytes?
A type of lymphocyte preprogrammed to produce one antibody against one antigen; transforms into a plasma cell when it recognizes an antigen and releases antibodies (immunoglobulins) via humoral immunity; phagocytes then engulf and destroy the antibody-covered antigens.
What are the functions of CD4 and CD8 surface markers?
Antigen coreceptors (they don't recognize the pathogen, they recognize the MHC)
Are NK cells part of the innate or adaptive immune systems?
Both
How do CD4+ T lymphocytes become terminally differentiated?
By cytokine production. A CD4+ T lymphocyte that has yet to be differentiated to TH1 or TH2 is called TH0.
How are T cells categorized?
By surface proteins and functions. T cells can be CD4+ or CD8+. CD4+ is further categorized into TH0, TH1, and TH2.
How do CD8+ T lymphocytes become terminally differentiated?
CD8+ cells are terminally differentiated into CTLs (cytotoxic T cells).
What are the effector functions of CD8+ cells?
Cell-mediated response to intracellular pathogens. They kill target cells through the release of cytotoxic enzymes and receptor-ligand induced apoptosis. Killing includes infected host cells, tumor cells and incompatible grafted/transplanted tissues. Remember: Killing is of target cells, not direct killing of pathogens.
What are memory B cells?
Cells that develop from naïve B cells activated by antigen & return to s resting state waiting to respond upon second interaction with a specific antigen.
What is the effector function of terminally differentiated CD4+ cells?
Cytokine production. TH1 and TH2 have different cytokine profiles for different types of pathogens.
What isotype switches are stimulated by TH2 cells?
From IgM to IgG1, IgE and IgA
What isotype switches are stimulated by TH1 cells?
From IgM to IgG2 and IgG3, and IgA
What cytokine inhibits TH2 differentiation?
IFN-gamma. It is produced by TH1.
Which cytokine, which it not produced by T cells, favors TH1 differentiation and why?
IL-12 is produced by dendritic cells, macrophages and neutrophils, and favors differentiation of TH1 because TH1 cells stimulate CD8+ Tcells for a cell-mediated response to intracellular pathogens.
What cytokines are made by TH1 cells?
IL-2, INF-gamma and TNF-B
What cytokines inhibits TH1 differentiation?
IL-4 and IL-10. Both are produced by TH2.
What cytokines are made by TH2 cells?
Interleukins 4,5,6,10
What is the purpose of IFN-gamma that is produces by NK cells?
It has antiviral effect by stimulating cytotoxic activity of Tc cells and it activates macrophages.
What is humoral response?
It is an immune response involving the transformation of B cells to plasma cells. Antibodies are secreted by B cells that are simulated by helper T cells (TH2). The antibodies bind to a specific antigen. This forms an antibody-antigen complex that then can be removed by a macrophage. Targets EXTRAcellular pathogens.
How do NK cells destroy antigens bound by antibodies?
Killing is via ADCC when Fc-gamma receptors on the cell surface bing IgG-coated antigen.
What are natural killer cells?
Large granular lymphocytes that do not have TCR or BCR (no antigen receptor). Instead, they have an Fc-gamma receptor so that they recognize antibodies with antigen bound.
What MHC class is recognized by CD8+ T cells?
MHC I
What MHC class is recognized by CD4+ T cells?
MHC II Tip: MHC *II* is recognized by CD4+ which has *2* subclasses (TH1, TH2)
What are killer inhibitory receptors?
NK cells must be told NOT to kill by a signal sent through killer inhibitory receptors. Class I MHC tells NK that the cell is normal by interacting with the inhibitory receptor. Viruses, for whatever reason, downregulate MHC I, and therefore the NK cell's inhibitory receptor receives no signal, and proceeds to destroy viral infected cells.
Do NK cells directly kill pathogens?
No, the killing is of the target cell.
What are the two options for B cell differentiation?
Plasma or memory cells
What is a T lymphocyte?
T Lymphocytes (T cells)- thymus hormones differentiate hemocytoblasts into T cells and make them immunocompetent: they can bind to antigens that are presented to them by other cells. 70-80% of all lymphocytes are T cells.
What is a TCR?
T cell receptor. All T cells have them and they are specific for a particular antigen. They are specific for a single peptide on the antigen (8-10 a.a. stretches)
What are TH0 cells?
T helper cells that have been activated but not differentiated.
What type of T helper cell would predominate in viral infections?
TH1...for INTRAcellular pathogens!
What T helper cell type is involved in allergic reactions?
TH2. Many anti-allergic meds shift immune profile from predominance of TH2 to TH1.
What are plasma cells?
Terminally differentiated B cells that become antibody factories. Each plasma cell produces antibodies with specificity only for that single antigen.
Other than Fc-gamma, what receptor do NK cells express?
The IL-2 receptor, which allows NK cells to proliferate in response to very low levels of IL-2. Remember: TH1 cells produce IL-2.
How do B cells present antigen?
The antigen binds to the BCR (a membrane bound antibody) and is endocytose, processed and presented on MHC molecules to T cells. An alternative method is that B cell PRRs recognize PAMPs.
How do NK cells destroy tumor cells?
They recognize a protein, MICA, on surface of many cancer cells.
What is another name for T lymphocytes?
Thymocytes
What is the effector function of terminally differentiated CD8+ cells?
To kill infected host cells or tumor cells through the release of cytotoxic enzymes (cell-mediated response).
Does a T cell have both CD4 and CD8 markers?
Usually they are mutually exclusive
