Specific Immune Responses How the Immune System Handles Specific Antigens
Jan 20, 2016
Specific Immune Responses
How the Immune System Handles Specific Antigens
Specific Immunity
• Involves T and/or B Lymphocytes.
• B cells produce antibodies – proteins that bind to antigens.
• Antibodies circulate freely in the blood – Immunoglobulins (Ig).
• T cells contain receptors for antigens.
Specific Immunity
• Each antibody & T cell recognizes a different antigen.
• Small part of an antigen – epitope.
• A given antibody can only bind to one part of a particular virus or a particular bacterium (think lock and key).
Humoral Immunity
• Involves antibodies.
• B cells produce antibodies.
• Targets bacterial cells, bacterial toxins, freely circulating viruses, allergens.
Cell-Mediated Immunity
• Involves T cells.
• They recognize our tissues that have gone awry or parasitic eukaryotes.
• Host cells infected with bacteria or viruses, cancerous cells, transplanted tissues, fungi, protists, worms.
Antigens
• Foreign substances that provoke an immune response.
• Usually protein or polysaccharide.
• Can be bacterial capsules, cell walls, flagella, secreted toxins, etc.
• Can be viral protein coat.• Can be pollen, surface of cells in transplanted
tissues/fluids, components of animal saliva, oils of plants, antibiotics, etc.
Antibodies• Structure: 4 protein
chains – 2 heavy and 2 light.
• Constant region & variable region.
• Variable regions bind to antigen.
• Each B cell produces antibodies with a unique variable region.
• There are 5 types of constant regions.
• Complement proteins & some WBCs can bind to constant
regions of antibodies that are bound to antigen.
Antibody (Ig) Classes
• IgG:
• Most prevalent Ig in blood
• Can leave blood and enter tissues; maternal IgG can cross placenta
• Target circulating virus, bacteria, bacterial toxins; stimulate complement and phagocytosis
• Long-lived (can indicate past exposure)
Antibody (Ig) Classes
• IgM:• Usually a complex of 5 antibodies held
together by J polypeptide• Tend to remain in blood; can be found on
surface of B cells• Responds to ABO blood antigens
(transfusion)• Stimulates the aggregation of antigen• Part of early response; short-lived
IgM
Antibody (Ig) Classes
• IgA:• Most common Ig in body as a whole• Found in mucous membranes, mucus,
tears, saliva, breast milk (esp. colostrum), other secretions
• Short-lived• Most effective as a dimer• Fights off infections in respiratory system,
GU and GI tracts
IgA
Antibody (Ig) Classes
• IgD:
• Circulate, but unknown function in blood
• Also found on surfaces of B cells
Antibody (Ig) Classes
• IgE:
• Constant region binds to mast cells and basophils
• Stimulate release of histamine when bound to antigen
• Antigen binding also stimulates the recruitment of phagocytes
Outcomes
• Agglutination – clumping of antigen-antibody complexes aids phagocytes; IgM is especially effective.
• Opsonization – coating of antigen with antibody also eases phagocytosis.
• Neutralization – antibody may bind to key epitope, such as the part of the virus that binds to a host cell (interference).
Outcomes
• Trigger complement – complement proteins quickly recognize most antigen-antibody complexes; lysis and/or inflammation can result.
B Cell Selection
• Enormous number of B cells are needed to protect against an infinite number of different antigens.
• During infection many copies (clones) of a particular B cell is needed.
• The body cannot keep too many of any particular B cell on hand at any one time.
• Instead, proliferation of specific B cells occurs in response to exposure to its matching antigen.
B cell Selection
• B cells tend to remain in lymph nodes and spleen – they wait for antigen to come to them.
• IgM and IgD act as antigen receptors on B cell surfaces.
• Proliferation of the B cell is stimulated by IgM or IgD binding to antigen.
B cell Differentiation
• Clonal selection – a particular clone is selected to proliferate by the antigen.
• Clones that actively produce antibody are known as plasma cells.
• A small number of clones become memory cells.
• Memory cells are stored for future use.
Immunological Memory
• Memory cells can persist in the lymph nodes and spleen for decades.
• Only a small number is needed of each memory cell.
• Memory cells respond quickly and strongly to secondary infections.
• IgG production is especially high during secondary infections.
Cell-Mediated Immunity
• Mainly responds to intracellular antigens.
• Involves a wide array of chemical signals, known as cytokines.
• Cytokines can either stimulate an immune response or inhibit one.
Cytokines
• Interleukins (IL) carry signals from one WBC to another.
• Chemokines stimulate the movemnet of WBCs to a site of infection.
• Interferons stimulate anti-viral activity.
• Tumor Necrosis Factor (TNF).
• Colony Stimulating Factor (CSF).
T cell Proliferation
• T cells are selected in the same way as B cells.
• Some T cells are designated as memory cells.
T Cells
• Helper T cells (TH), Cytotoxic T cells (TC), Delayed Hypersensitivity T cells (TD), Suppressor T cells (TS).
• CD receptors can also define T cells: CD4 (helper, memory) and CD8 (cytotoxic, suppressor).
T Cells
• Each T cell is specific for a specific antigen/epitope.
• The epitope must be presented on the surface of an antigen-presenting cell (APC) – macrophages (or dendritic cells).
• Epitope may be on surface of infected cell.
Antigen-Presenting Cells
• Ingest antigen by phagocytosis.
• Digest proteins into small peptides.
• Display these peptides along with the major histocompatibility complex (MHC) on their surface.
• T Cells Receptors (TCR) – recognize MHC-antigen complexes.
TH Cells
• Secrete cytokines when stimulated by antigen.
• These cytokines stimulate other immune cells.
• Cytokines from TH1 cells target macrophages, CD8 T cells, natural killer cells.
• Cytokines from TH2 cells target B cells.
TH Cells
• TH Cell binding to APC causes APC to secrete IL-1.
• IL-1 stimulates TH Cell to secrete IL-2.
• IL-2 binds to receptors on that same TH Cell.
• TH Cell reproduces – specific because only those bound to antigen have IL-2 receptors (environmental control of gene expression).
• TH Cell clones produce cytokines to recruit more T cells and B cells.
TC Cells
• TC Cells also bind to MHC-antigen complex - on surface of target cells.
• Binding stimulates the TC Cells to secrete perforin, a protein which forms pores in the target cell’s membrane.
• These pores induce the lysis of the target cell.
B and T Cells Work Together
• B cells can work alone when the antigen is LPS or capsule polysaccharides.
• More often, though, TH cells bound to APC release IL-2 to recruit B cells.
• The recruited B cells develop into plasma cells and make antibodies against the antigen .