Bone marrow, thymus, spleen, liver, and lymph nodes {immune system, organ}| protect body from invading organisms.
self
Immune system can recognize organism cells, because all body cell-membrane outsides have same cell-recognition glycoproteins.
antibodies
Immune-system cells can recognize antibodies, because antibodies complex with cell-recognition glycoproteins.
humoral immunity
Immune system can kill bacteria and viruses in cell fluids.
cellular immunity
Immune system can absorb body cells that have been damaged by viruses or bacteria and regulate immune system.
evolution
Humoral immunity and cellular immunity both come from same precursor cells during development.
acidity
Stomach acidity and urine acidity kill and suppress bacteria.
Several thousand different antigen-specific B cells are present {clonal-selection theory}, even in fetus.
Wax {ear wax} {wax, ear} can block ear bacteria.
Lymph, leukocytes, bacteria, and tissue leave residues {pus}|.
After healing, lymphocytes change to connective tissue {scar tissue}|.
Tears {tears} are antibacterial.
Organs from other organisms can replace same organs in individuals {transplantation}|. Immune system typically attacks foreign tissue.
Humoral immunity uses immune-system cells {macrophage}| that find antigens and process them.
Precursor cells {hemopoietic stem cell} (HSC), trapped inside bone-marrow special-cell {stromal cell} pockets, make all immune-system cells.
Hemopoietic stem cells divide to make cells {multipotent progenitor cell} (MPP) that move out of stroma and make hemopoietic stem cells that stay in stroma. Multipotent progenitor cells divide into myeloid progenitors and lymphoid progenitors. Myeloid progenitors divide into granulocytic/monocytic precursors and megakaryocytic/erythrocytic precursors. Lymphoid progenitors divide into B-cell precursors and T-cell precursors.
Mammalian immune-system bone-marrow cells {B cell}| synthesize and secrete antibodies and migrate to spleen, liver, and lymph nodes. If antigens meet B cells with correct antibodies, B cells transform into plasma cells.
antibodies
B cells differentiate from making IgM to making IgG to making IgA. B cells transpose variable region, located far from constant-region gene, to joining region, to make different antibodies. Enhancer activates only one variable-gene promoter. Vertebrate immune-system B cells use controlled transposition to make one antibody. Antibodies have constant regions. Various joining regions can attach to constant region. Various variable regions, located far from constant region in genome, can transpose to joining region.
Cells {memory cell} can take information back to lymph nodes or spleen, where memory cells change to plasma cells.
Cells {plasma cell}| can come from B cells. Plasma cells are lymphocytes that make antibodies and bind to foreign proteins. They make only one antibody type, which reacts with antigen to form precipitates for phagocytization. Humoral system makes 2000 antibodies per second for several days to prevent re-infection. Immature plasma cells in fetus that make antibodies against self normally die, leaving only antibodies against foreign molecules at birth.
IgD are on B-cell surfaces. IgE starts cells {mast cell}| that make histamine.
Immune-system cells {natural killer cell} can attach to B cells at temporary synapses to check if they are functioning.
In third and fourth pharyngeal pouch, thymus immune-system cells {T cell}| produce lymphokines from precursors. T cells can phagocytize foreign cells and viruses {cellular immunity, T cell}. Cytotoxic T cells absorb damaged cells.
cell surface
T cells have surface protein receptors. These glycoproteins can have alpha, beta, gamma, and delta subunits. Receptor genes for these proteins are similar to immunoglobulin genes. Immunoglobulin superfamily has similar constant, joining, diverse, and variable regions and similar promoters.
T cells {CD4+ T lymphocyte} {helper T cell} can have cell-surface CD4-protein receptors {co-receptor}, which assist T-cell receptors. Helper T cells have T-cell receptors.
process
Helper T cells start disease-organism killing. Helper T cells secrete lymphokines, such as interleukin, interferon, colony-stimulating factor, and tumor necrosis factor. Lymphokines activate cytotoxic T cells, signal B cells to make antibodies, attract macrophages and platelets with chemotactic factor, multiply helper T cells, and multiply immune precursor cells.
regulatory T cells
5% to 10% of helper T cells have CD25 surface protein and Foxp3 transcription factor and inhibit autoreactive CD4+ T lymphocytes.
problems
CD4+ T lymphocytes can alter to cause multiple sclerosis, insulin-dependent diabetes of youth, and rheumatoid arthritis.
Helper T cells {regulatory T cell} {CD4+CD25+ T cell} {T-reg cell} {T regulatory cell} can inhibit helper-T-cell immune responses, rather than secrete cytokines or engulf infected cells. 5% to 10% of CD4+ T lymphocytes are regulatory T cells.
receptors
Regulatory T cells have T-cell receptors, CD4-protein receptors, and CD25 surface proteins, which are in interleukin-2 receptors. Interleukin-2 excites regulatory T cells.
transcription
They have Foxp3 transcription-factor protein, which makes molecules that can disable autoreactive T cells.
Perhaps, antigen-specific receptors are stronger than the ones for autoreactive CD4+ T lymphocytes. Perhaps, regulatory T cells inhibit antigen-presenting cells from showing antigen. Perhaps, regulatory T cells cause antigen-presenting cells to release inhibitory cytokines. Perhaps, regulatory T cells inhibit autoreactive CD4+ T lymphocytes directly.
problems
Foxp3-gene mutation can cause immune dysregulation polyendocrinopathy enteropathy X-linked chromosome syndrome {IPEX syndrome} and autoreactive immune systems. Scurfy mice have autoreactive immune systems.
T cells {dendritic cell} can have surface molecules that bind to non-self proteins and attract T cells to breakdown protein. Then they usually die.
Cells {antigen-presenting cell} can contact T cells, to present protein fragments {supramolecular activation cluster, antigen} that they removed from viruses or bacteria, and so activate T cells. Supramolecular-activation clusters have outer rings for adhesion and central spots for recognition. Proteins move to form patterns, using cytoskeletons.
B cells and T cells make antibodies against antigens {adaptive immune system}.
T cells can phagocytize foreign cells and viruses {cell-mediated system} {cellular immunity}|. After contacting cells having different MHC surface proteins, lymphocytes change to macrophages, as antigen combines with special RNA, which engulf foreign cells. Memory cells take information back to lymph nodes and spleen, where memory cells change to plasma cells.
Immune system can kill bacteria and viruses in cell fluids {humoral immunity}| {humoral system}. Plasma cells make 2000 antibodies per second for several days to prevent reinfection.
The first time {primary immune response} bodies react to new antigens has greatest reaction {immune response}|. Later antigens cause reactions {secondary immune response}.
Natural killer cells can attach to B cells at temporary synapses {immune synapse}, to check if they are functioning. Natural-killer-cell receptor proteins check B-cell surface proteins. If no reception, acidic organelles move to synapse and inject chemicals to kill cells. Antigen-presenting cells contact T cells {supramolecular activation cluster, immunity} at immune synapses to present protein fragments that they removed from viruses or bacteria and activate T cells. Immune-synapse outer ring is for adhesion, and central spot is for recognition. Proteins move to form patterns, using cytoskeletons.
Body cells can react to pathogens {innate immune system}.
cells
Phagocytes include monocytes and dendritic cells. Monocytes become macrophages.
receptors
Pathogen molecules cause inflammation. Phagocyte Toll-like receptors recognize molecule types.
cytokines
Inside cells, TLRs make MyD88, Mal, Tram, and/or Trif. These make NF-kappaB, which enters cell nucleus to start cytokine production.
dendritic cells
After phage ingestion, dendritic cells carry phage fragments to lymph nodes to inform T cells.
Spleen, lymph nodes, liver, and bone marrow blood-vessel sinusoid cells phagocytize foreign cells {reticuloendothelial system}.
Immune system has rapid generalized responses {sickness response}| {acute phase response}.
purpose
Sickness response creates or saves energy.
process
Stress causes hypothalamus, pituitary, adrenal gland, and sympathetic nervous system to release hormones and transmitters, which bind to immune-cell receptors and regulate immunity. Activated immune cells release pro-inflammatory cytokines that affect neurons and glia, which coordinate hormone, behavior, and physiological changes related to fever. Physiological changes are fever, blood-ion-concentration reduction, increased white-blood-cell replication, and increased sleep. Blood-ion-concentration reduction denies minerals required by replicating bacteria and viruses. Behavior changes decrease social interaction, exploration, sexual activity, and food and water intake. Hormone changes increase hypothalamus, pituitary, adrenal, and sympathetic-nervous-system hormone release.
fever
Fever raises body temperature, so bacteria and viruses do not replicate rapidly, bacteria do not form protective outer coats, white blood cells replicate rapidly, and destructive enzymes function efficiently.
slow response
Immune system has slow selective response, which makes antibodies [Maier et al., 1994] [Maier and Watkins, 1998] [Maier and Watkins, 2000].
glia
Glia can act like immune cells.
Peptides {hexapeptide} can have shapes similar to 20 others, so they all bind same antibody.
Muropeptides {lectin} bind to NOD, such as NOD2, and NALP intracellular receptors and trigger cytokines and/or transcription factors. Lectins include mannose-binding lectin.
Helper T cells make molecules {cytokine}| that attract neutrophils and monocytes, which become macrophages: {colony-stimulating factor} {granulocyte-macrophage colony-stimulating factor} (GMCSF) {interleukin}. Tumor necrosis factor alpha {tumor necrosis factor} increases inflammation. Inside cells, Toll-like receptors make MyD88, Mal, Tram, and/or Trif. These make NF-kappaB, which enters cell nucleus to start cytokine production. Cytokines include interleukin-1, interleukin-6, interleukin-8, interleukin-12, and tumor necrosis factor-alpha. Interleukin-1 increases inflammation. Interleukin-6 activates B cells. Interleukin-8 is signal to neutrophils. Interleukin-12 activates T cells. Cytokines attract monocytes and neutrophils. Monocytes become macrophages.
Cells inflamed by injury, allergens, antigens, or invading microorganisms release 8-kDa to 16-kDa soluble proteins {chemokine}, to attract monocytes and granulocytes. Humans have 50 chemokines.
types
Alpha chemokines have amino acids between first two cysteines and have two other cysteines. Beta chemokines have no separation between first two cysteines and have two other cysteines. Gamma chemokines have two cross-linked cysteines. Lymph nodes, lungs, liver, and bone marrow express factors {stromal-cell-derived factor 1} from genes {SDF-1 gene} {CXCL12 gene}.
receptors
Chemokines bind to chemokine receptors {G protein-linked receptor}. Chemokine receptors (CXCR2) (CXCR4) (CCR7) include chemokine receptor 5 (CCR5), used by HIV-1.
receptors: effects
Binding to receptors causes adhesion-protein {B integrin} rearrangement, to increase adhesion to blood-vessel endothelial cells. Later, leukocytes pass between endothelial cells into tissue. Leukocytes use pseudopods and actin movement to migrate along chemokine concentration gradient. High chemokine concentration makes leukocytes produce cytokines, release granule contents, induce intracellular F-actin polymerization, form pseudopods, increase endothelial and other cells, promote vascularization, remodel tissue, heal wounds, and lyse lymphocytes.
Macrophages and endothelial cells make proteins {S100 protein}, such as S100A8 and S100A9, that signal for more macrophages to come.
Tumor necrosis factor, interleukin-l, and interleukin-6 cytokines {pro-inflammatory cytokine} cause sickness responses [Maier and Watkins, 1998] [Watkins and Maier, 1999] [Watkins and Maier, 2002].
In third and fourth pharyngeal pouch, thymus helper T cells secrete peptides {lymphokine}, such as interleukin, interferon, colony-stimulating factor, and tumor necrosis factor. Lymphokines activate cytotoxic T cells, signal B cells to make antibodies, attract macrophages and platelets with chemotactic factors, multiply helper T cells, and multiply immune precursor cells.
Helper T cells secrete lymphokine peptides, such as interleukin, interferon, colony-stimulating factor, and tumor necrosis factor. Lymphokines activate cytotoxic T cells, signal B cells to make antibodies, attract macrophages and platelets {chemotactic factor}, multiply helper T cells, and multiply immune precursor cells.
T cells have cell-surface protein receptors {immunoglobulin superfamily, antibody}. These glycoproteins can have alpha, beta, gamma, and delta subunits. Receptor genes for these proteins are similar to immunoglobulin genes. They have similar constant, joining, diverse, and variable regions and similar promoters. Immunoglobulin superfamily includes cell-adhesion proteins {neural-cell adhesion molecule}, growth-factor receptors, and lymphokine receptors. MHC genes are similar to genes for antibodies and T-cell receptors.
Antibodies {abzyme} can act like enzymes and bind to reaction transition states. 10% of such binding affects reaction rates.
Immune-system B cells make one antibody type {allelic exclusion} and secrete it into blood.
One antibody arm can bind to one molecule, and other arm to another molecule {bispecific antibody}.
Variable antibody regions have only three parts that actually bind to antigen {complementarity determining region} (CDR). Variable regions otherwise just align CDRs. Humanized antibodies use human antibodies with CDRs from monoclonal mice.
Toxins can replace antibody regions {effector region} used to determine immunoglobulin type, to deliver agents only to correct sites.
Antibody variable regions can attach to different constant regions for different immunoglobulin types {class switching}, so all immunoglobulin types use same antibody.
Antibodies have two longer proteins {heavy chain}. Heavy chains have variable regions at arm ends, diverse region, joining region, and three constant regions. Single genes are for constant regions. Heavy chains can come from 20 diverse-region genes. Heavy chains can come from four joining-region genes. Thousands of genes code for variable regions. How regions bind together also varies.
Y
Two heavy chains join in middle to make Y shapes.
types
Heavy chains have five types: alpha, gamma, delta, epsilon, or mu.
antibody types
Heavy-chain type determines antibody type: immunoglobulinA or IgA, immunoglobulinG or IgG, immunoglobulinD or IgD, immunoglobulinE or IgE, or immunoglobulinM or IgM. IgA binds to antigens in saliva, tears, and intestines. IgG and IgM go into blood and bind to antigens, bound antigen binds to cells, and IgG and IgM activate immune-system macrophages, which eat cells with bound antigen. IgD are on B-cell surfaces. IgE starts mast cells that make histamine. Perhaps, histamine defends against parasites. Immunoglobulin-E can attack worms.
Antibodies have two shorter proteins {light chain}. Light chains have variable regions at arm ends, joining region, and constant region. Single genes are for constant regions. Light chains can come from five joining-region genes. Thousands of genes code for variable regions. How regions bind together also varies. Light chains parallel Y arms on outsides. Light chains have two types: kappa or lambda.
Immune-system genes rearrange in early infancy. Antibody gene can join second gene {joining gene} by deleting DNA between them. Joining genes join trunk gene, which determine mobility level. Joined genes determine antigen.
Immune-system genes rearrange in early infancy. Antibody gene can join joining gene by deleting DNA between them. Joining genes join gene series {trunk gene}, which determine mobility level. Joined genes determine antigen.
Beta2-microglobulin and other cell-surface glycoproteins {major histocompatibility protein}| (MHC) can be for cell recognition.
number
Humans can have 100,000 different surface-protein sets.
polymorphism
Cell-surface glycoproteins can be highly polymorphic.
genes
MHC genes are similar to genes for antibodies and T-cell receptors {immunoglobulin superfamily, MHC}. MHC genes do not vary through rearrangement. MHC Class I genes are expressed in all cells. MHC Class II genes make glycoproteins for B cells and macrophages. Other MHC genes make blood-complement proteins and other cell-surface proteins.
receptors
Cytotoxic T cells recognize glycoproteins.
metabolism
MHC Class I glycoproteins cut bacterial and viral antigens into peptides, which then bind to cleft in MHC Class II glycoproteins. Helper T cells recognize antigen/MHC Class II complexes. Complement proteins CD4 and CD8 bind MHC to receptors at constant antibody regions and signal T cells to activate.
T cells can have antigen receptors {T cell receptor} (TCR).
Cell-surface proteins can have classes {tissue typing}|.
Phagocyte-cell receptors {Toll-like receptor} (TLR) can recognize lipopeptides. TLR1 detects bacterial lipopeptides and parasite GPI-anchored proteins. TLR2 detects Gram-positive-bacteria cell-wall lipoteichoic acids. TLR3 detects virus double-stranded RNA. TLR4 detects Gram-negative bacteria by binding to lipopolysaccharide. TLR5 detects bacteria-flagella flagellin. TLR6 detects fungi zymosan. TLR7 detects virus single-stranded RNA. TLR8 detects virus single-stranded RNA. TLR9 detects bacterial and virus CpG sequences.
metabolism
Inside cells, TLRs make MyD88, Mal, Tram, and/or Trif. These make NF-kappaB, which enters cell nuclei to start cytokine production.
evolution
TLR are in plants and animals. Tobacco has N protein that detects tobacco mosaic virus. TLR probably started in one-celled organisms.
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Date Modified: 2022.0225