Specific Immune Responses How the Immune System Handles Specific Antigens.

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 .