Lecture 4 Antibody Immune Response (Step 4: Proliferation &…
Antibody Immune Response
T-dependent Antibody Immunity
When antibody responses depend on interaction with helper T cells
Independent responses: act against molecules with multiple repeating epitodes (Ex. Polysaccharides)
The dependent responses begin with actions from antigen presenting dendritic cells (APC)
Then endocytosis and processing of the antigen
This is where the dendritic cell presents epitopes in conjunction with it’s MHC (major histocompatibility complex) proteins
The APC will induce the specific T lymphocyte with the TCR complimentary to MHC H-epitope complex
The activated Th2 cell must in turn induce the specific B cell that recognize the same antigen
Lymph nodes facilitate
Cytokines mediate interactions among the antigen cells and lymphocytes
This increases the chance that the correct cells find each other
We will take a look closer of dependent response
Step 1: Antigen presentation for Th activation and Proliferation
After the dendritic cells acquired antigens in skin or mucous membranes it moves by lymph to local node
Helper T cells pass through lymph node and survey all resident APC’s for compliment epitopes with MHC II proteins
Immunologists estimate every lymph browses the dendritic cell in every node every day
Once they’ve established a immunological synapse CD4 molecules in the membrane rafts of the Th cells cytoplasmic membrane recognize and bind to MHC proteins
This will lead to the stable version of the synapse
Helper T cells need a 2nd signal to help prevent accidental inducement of an immune response
APC departs a 2nd signal by displaying an integral membrane protein in the synapse
This will induce TH cells to produce clones
Step 2: Differentiation of helper T cells into Th2
The cytokine interleukin 4 (IL-4) acts as a signal to the Th cells to become type 2 helper T cells (Th2 cells).
Immunologists don’t know the source of IL-4 but suggest it is secreted by innate cells (ex: mast cells)
Or secreted later by a response of Th cells themselves
Step 3: Activation of B cells
B cells and newly formed Th2 cells survey one another
A Th2 cell binds to B cell with an MHC II protein- epitope complex and compliments the TCR of the Th2 cell
CD4 glycoprotein will stabilize immunological synapse.
Th2 cells secrete IL-4 that induces selected B cell to move to the cortex of the lymph node
A Th cell in contact with MHC II protein-epitope on the B cell expresses a new gene product and inserts a protein called CD40L into the cytoplasmic membrane
CD40L binds to CD40, found on B cells
Provides a second signal in immunological synapse and triggers B cell activation
These processes are called clonal selection b/c in effect they select a specific B cell.
Step 4: Proliferation & Differentiation of B cells
Then the selected B cell proliferates rapidly to produce a population of cells (clones) that make up a primary follicle in lymph node.
Clones then differentiate into two types of cells:
Memory B cells
Antibody-secreting plasma cells
Most differentiated B cells become plasma cells
The plasma cells descend from single activated B cells and secrete antibodies with binding sites identical to one another and compliment to specific antigen recognized by the parent cell
Plasma clones replicate and their antibodies will be slightly different variable regions
They secrete more survival advantaged antibodies to fight the next epitopes
As immune response progresses the plasma cell antibodies get better.
Each plasma cell produces different classes of antibodies
Begin: secrete IgM and class switches to Ige, IgA, or IgG
Controlled by Th cells and is irreversible
Secrete own weight in IgG every day
Individual plasma cells die in a few days b/c of their metabolic rate
Antibodies will remain for weeks
The descendants remain for years to help with adaptive responses
Memory Cells and the Establishment of Immunological Memory
A small percentage of the cells produced during B cell proliferation do not secrete antibodies but survive as memory B cells. That is, long-lived cells with BCRs complementary to the specific epitope that triggered their production.
In contrast to plasma cells, memory cells retain their BCRs and persist in lymphoid tissues, surviving for more than 20 years, ready to initiate antibody production if the epitope is encountered again.
Because the body produces an enormous variety of T and B cells, a few Th cells and B cells bind to and respond to epitopes of tetanus toxoid.
Tetanus toxoid- inactivated tetanus toxin, which is used for tetanus immunization.
In a primary response, relatively small amounts of antibodies are produced, and it may take days before sufficient antibodies are made to completely eliminate the toxoid from the body.
Though some antibody molecules may persist for three weeks, a primary immune response basically ends when the plasma cells have lived out their normal lifespans.
Memory B and T cells surviving in the lymphoid tissue, constitute a reserve of antigen-sensitive cells that become active when there is another exposure to the antigen, in this case, toxin from infecting tetanus bacteria. (Exposure may occur years later)
Tetanus toxin produced during the course of a bacterial infection directly stimulates a population of memory cells, which proliferate and differentiate rapidly into plasma cells without having to be activated by antigen-presenting cells.
Newly differentiated plasma cells produce large amounts of antibody within a few days it can cause disease
Because many memory cells recognize and respond to the antigen, such a secondary immune response is much faster and more effective than the primary response.
As you might expect, a third exposure (tetanus toxin or to toxoid in an immunization booster) results in an even more effective response. Enhanced immune responses triggered by subsequent exposure to antigens are memory responses, which are the basis of immunization.