Hstk 4
Innate immunity (also called natural, or native, immunity) is mediated by cells
and proteins that are always present and poised to fight against microbes, being
called into action immediately in response to infection. There are two types of
adaptive immune responses: humoral immunity, mediated by soluble proteins
called antibodies that are produced by B lymphocytes (also called B cells
extracellular microbes), and cell-mediated (or cellular) immunity, mediated by T
lymphocytes (also called T cells intracellular microbes).
The cells of the immune system consist of lymphocytes, which recognize antigens
and mount adaptive immune responses; specialized antigen-presenting cells (APCs),
which capture and display microbial and other antigens to the lymphocytes; and
various effector cells, whose function is to eliminate microbes and other antigens.
Each T or B lymphocyte expresses receptors for a single antigen. Thymus-derived,
or T, lymphocytes are the effector cells of cellular immunity and the “helper cells”
for antibody responses to protein antigens. It is now known that the normal function
of MHC molecules is to display peptides for recognition by T lymphocytes. CD4 and
CD8 are expressed on distinct T cell subsets and serve as coreceptors for T cell
activation. During antigen recognition, CD4 molecules on T cells bind to invariant
portions of class II MHC molecules on selected APCs; in an analogous fashion, CD8
binds to class I MHC molecules. CD4+ T cells are “helper” T cells because they
secrete soluble molecules (cytokines) that help B cells to produce antibodies (the
origin of the name “helper” cells) and also help macrophages to destroy
phagocytosed microbes. CD8+ T cells can also secrete cytokines, but they play a
more important role in directly killing virus-infected or tumor cells, and hence are
called “cytotoxic” T lymphocytes (CTLs). Other important invariant proteins on T
cells include CD28, which functions as the receptor for molecules that are induced
on APCs by microbes (and are called costimulators), and various adhesion
molecules that strengthen the bond between the T cells and APCs and control the
migration of the T cells to different tissues.
The human MHC, known as the human leukocyte antigen (HLA) complex,
consists of a cluster of genes on chromosome 6. 2 categories of MHC gene products:
Class I MHC are encoded by three closely linked loci, designated HLA-A, HLA-B, and
HLA-C. In general, class I MHC molecules bind and display peptides derived from
proteins synthesized in the cytoplasm of the cell (e.g., viral antigens). Because class
, I MHC molecules are present on all nucleated cells, all virus-infected cells can be
detected and eliminated by CD8+ CTLs. Class II MHC molecules are encoded by
genes in the HLA-D region. Class II MHC expression is restricted to a few types of
cells, mainly APCs (notably, dendritic cells [DCs]), macrophages, and B cells. In
general, class II MHC molecules bind to peptides derived from proteins synthesized
outside the cell (e.g., those derived from extracellular bacteria) and ingested into
the cell. This property allows CD4+ T cells to recognize the presence of extracellular
pathogens and to orchestrate a protective response. Different MHC alleles bind to
different peptide fragments; the expression of many different MHC molecules allows
each cell to present a wide array of peptide antigens. The combination of HLA
alleles for each person is called the HLA haplotype. Many autoimmune diseases are
associated with particular HLA alleles.
Bone marrow–derived B lymphocytes are the cells that produce antibodies and are
thus the effector cells of humoral immunity. B cells recognize antigen by means of
membrane-bound antibody of the immunoglobulin M (IgM) class, expressed on the
surface together with signaling molecules to form the B cell receptor (BCR) complex.
CD21 (or CR2) recognizes a complement breakdown product that frequently is
deposited on microbes and promotes B cell responses to microbial antigens. After
stimulation, B cells differentiate into plasma cells, which secrete large amounts of
antibodies, the mediators of humoral immunity. There are five classes, or isotypes,
of immunoglobulins: IgG, IgM, and IgA constitute more than 95% of circulating
antibodies. IgA is the major isotype in mucosal secretions; IgE is present in the
circulation at very low concentrations and also is found attached to the surfaces of
tissue mast cells; and IgD is expressed on the surfaces of B cells but is not
secreted. NK cells have two types of receptors—inhibitory and activating. The
inhibitory receptors recognize self class I MHC molecules, which are expressed on
all healthy cells, whereas the activating receptors recognize molecules that are
expressed or upregulated on stressed or infected cells or cells with DNA damage.
They do not have specificities as diverse as do T cells or B cells.
Dendritic cells (DCs), express high levels of class II MHC and T cell costimulatory
molecules and function to capture and present antigens to T cells. Where? Under
epithelia, T cell zones of lymph nodes, interstitium of non-lymphoid organs. One
subset of DCs is called plasmacytoid DCs because of their resemblance to plasma
cells. These cells are present in the blood and lymphoid organs, and are major
sources of the antiviral cytokine type I interferon, produced in response to many
viruses. The second type of cells with dendritic morphology are follicular dendritic
cells (FDCs). These cells are located in the germinal centers of lymphoid follicles in
the spleen and lymph nodes. FDCs receptors for Fc tails of IgG molecules and
complement proteins. These cells display antigens to activated B lymphocytes in
lymphoid follicles and promote secondary antibody responses, but not involved in
capturing antigens for T-cells.
Innate immunity (also called natural, or native, immunity) is mediated by cells
and proteins that are always present and poised to fight against microbes, being
called into action immediately in response to infection. There are two types of
adaptive immune responses: humoral immunity, mediated by soluble proteins
called antibodies that are produced by B lymphocytes (also called B cells
extracellular microbes), and cell-mediated (or cellular) immunity, mediated by T
lymphocytes (also called T cells intracellular microbes).
The cells of the immune system consist of lymphocytes, which recognize antigens
and mount adaptive immune responses; specialized antigen-presenting cells (APCs),
which capture and display microbial and other antigens to the lymphocytes; and
various effector cells, whose function is to eliminate microbes and other antigens.
Each T or B lymphocyte expresses receptors for a single antigen. Thymus-derived,
or T, lymphocytes are the effector cells of cellular immunity and the “helper cells”
for antibody responses to protein antigens. It is now known that the normal function
of MHC molecules is to display peptides for recognition by T lymphocytes. CD4 and
CD8 are expressed on distinct T cell subsets and serve as coreceptors for T cell
activation. During antigen recognition, CD4 molecules on T cells bind to invariant
portions of class II MHC molecules on selected APCs; in an analogous fashion, CD8
binds to class I MHC molecules. CD4+ T cells are “helper” T cells because they
secrete soluble molecules (cytokines) that help B cells to produce antibodies (the
origin of the name “helper” cells) and also help macrophages to destroy
phagocytosed microbes. CD8+ T cells can also secrete cytokines, but they play a
more important role in directly killing virus-infected or tumor cells, and hence are
called “cytotoxic” T lymphocytes (CTLs). Other important invariant proteins on T
cells include CD28, which functions as the receptor for molecules that are induced
on APCs by microbes (and are called costimulators), and various adhesion
molecules that strengthen the bond between the T cells and APCs and control the
migration of the T cells to different tissues.
The human MHC, known as the human leukocyte antigen (HLA) complex,
consists of a cluster of genes on chromosome 6. 2 categories of MHC gene products:
Class I MHC are encoded by three closely linked loci, designated HLA-A, HLA-B, and
HLA-C. In general, class I MHC molecules bind and display peptides derived from
proteins synthesized in the cytoplasm of the cell (e.g., viral antigens). Because class
, I MHC molecules are present on all nucleated cells, all virus-infected cells can be
detected and eliminated by CD8+ CTLs. Class II MHC molecules are encoded by
genes in the HLA-D region. Class II MHC expression is restricted to a few types of
cells, mainly APCs (notably, dendritic cells [DCs]), macrophages, and B cells. In
general, class II MHC molecules bind to peptides derived from proteins synthesized
outside the cell (e.g., those derived from extracellular bacteria) and ingested into
the cell. This property allows CD4+ T cells to recognize the presence of extracellular
pathogens and to orchestrate a protective response. Different MHC alleles bind to
different peptide fragments; the expression of many different MHC molecules allows
each cell to present a wide array of peptide antigens. The combination of HLA
alleles for each person is called the HLA haplotype. Many autoimmune diseases are
associated with particular HLA alleles.
Bone marrow–derived B lymphocytes are the cells that produce antibodies and are
thus the effector cells of humoral immunity. B cells recognize antigen by means of
membrane-bound antibody of the immunoglobulin M (IgM) class, expressed on the
surface together with signaling molecules to form the B cell receptor (BCR) complex.
CD21 (or CR2) recognizes a complement breakdown product that frequently is
deposited on microbes and promotes B cell responses to microbial antigens. After
stimulation, B cells differentiate into plasma cells, which secrete large amounts of
antibodies, the mediators of humoral immunity. There are five classes, or isotypes,
of immunoglobulins: IgG, IgM, and IgA constitute more than 95% of circulating
antibodies. IgA is the major isotype in mucosal secretions; IgE is present in the
circulation at very low concentrations and also is found attached to the surfaces of
tissue mast cells; and IgD is expressed on the surfaces of B cells but is not
secreted. NK cells have two types of receptors—inhibitory and activating. The
inhibitory receptors recognize self class I MHC molecules, which are expressed on
all healthy cells, whereas the activating receptors recognize molecules that are
expressed or upregulated on stressed or infected cells or cells with DNA damage.
They do not have specificities as diverse as do T cells or B cells.
Dendritic cells (DCs), express high levels of class II MHC and T cell costimulatory
molecules and function to capture and present antigens to T cells. Where? Under
epithelia, T cell zones of lymph nodes, interstitium of non-lymphoid organs. One
subset of DCs is called plasmacytoid DCs because of their resemblance to plasma
cells. These cells are present in the blood and lymphoid organs, and are major
sources of the antiviral cytokine type I interferon, produced in response to many
viruses. The second type of cells with dendritic morphology are follicular dendritic
cells (FDCs). These cells are located in the germinal centers of lymphoid follicles in
the spleen and lymph nodes. FDCs receptors for Fc tails of IgG molecules and
complement proteins. These cells display antigens to activated B lymphocytes in
lymphoid follicles and promote secondary antibody responses, but not involved in
capturing antigens for T-cells.
