Immune response

T cells have receptors as well, transmembrane proteins expressed on the surface of the cell.  (Fig. 53.9)

How are B and T cells activated to destroy pathogens or cells carrying that antigen?

How does the immune system “remember” it has encountered an antigen before and mount a faster response the second time?

B cells make antibodies, kill or inactivate extracellular pathogens

- bacteria

- viruses outside cells

- worms

Cytotoxic T cells kill infected or cancerous cells (can also kill transplanted cells or RBCs)

Helper T cells – enhance both of above

Activating T cells

-          always happens when receptor on cell surface binds antigen

o   T cells recognize fragments of foreign molecules that are antigens

-          T cell activation

o   Two types of T cells, CD4 (helper) and CD8 cells (cytotoxic)

o   Both activated by presentation of antigen on a MHC molecule on the surface of a cell

o   CD4 cell activation (Fig.53.9)

§  Macrophages, dendritic and B cells phagocytize an antigen (might be an entire bacterium or virus, or just a molecule from one of those)

·         So only those cells can active CD4 cells!

§  Cell chops up the antigen into small fragments

§  Becomes an antigen presenting cell (APC)

§  Fragments are bound to MHC protein (class II)

·         MHC proteins are a family of proteins on cell surface which display antigens

§  APCs migrate to lymph tissues, especially lymph nodes

§  CD4 T cells touch the surface of APCs

·         If T cell receptor can bind MHC-antigen complex, CD4 T cell is activated

§  Activated CD4 T cells will become Helper T cells

o   CD8 cell activation

§  Very similar to CD4 cell activation

§  Receptor recognizes antigen bound on MHC (only class I)

·         presented by any cell infected with intracellular pathogen or cancerous and expressing antigens it shouldn’t

§  Becomes activated

§  Activated CD8 cells become cytotoxic T lymphocytes

·         Helper T cells help this with cytokines

Killing pathogens and cancerous cells

Cytotoxic T lymphocytes

-          bind and are activated by antigens presented by any cell in the body

-          cell might be infected with virus or might be cancer cell

-          T cell makes protein called perforin that makes a hole in membrane of other cell

-          Secretes enzymes into the other cell that cause that cell to kill itself (apoptosis)

Plasma cells (B cells)

-          when they are stimulated, they make and secrete antibodies

-          antibodies bind antigen (in native conformation)

-          can do several things

o   increase phagocytosis by leukocytes

o   for viruses, can cover so much of the outside of the virus that it can’t infect a cell

o   also activates complement system

§  like perforin, a bunch of proteins that poke hole in invading cell and kill it

§  complement proteins are constantly circulating in inactive form in blood, they are activated by antibody bound to antigen

Helper T cells

-          help B cells to be activated as noted above

-          help cytotoxic T cells by releasing cytokines that help activate CTLs

Memory

-          after antigen disappears, some CTLs, helper T cells, and plasma cells become memory cells

-          long lived – years or decades

-          if antigen is encountered a second time, have secondary immune response

o   much faster and stronger (Fig.53.12)

Stuff

Vaccines

-          give person exposure to weakened or killed pathogen (or just some proteins or other antigen from pathogen)

-          this doesn’t make them sick (or not very sick) but does stimulate immune response

-          next time you encounter antigen you vanquish it without even getting sick

-          so you are constantly being infected with mumps, measles, polio and all the rest, but your immune system kills it before it makes you sick

Autoimmune diseases

-          normally all B and T cells that have receptors that respond to your own molecules are eliminated

-          sometimes they aren’t or somehow generate immune response to molecules normally found in your body

-          then your immune system attacks your own body

-          MS, lupus, myasthenia gravis

Transplant rejection

-          your immune system recognizes transplanted tissue as foreign

-          attacks it

-          so people with transplants are on serious immunosuppressive drugs

-          MHC – these are highly variable from person to person and it is often this molecule that is recognized as “foreign” – ironic!

Allergies

-          for unknown reasons sometimes people produce antibodies in the IgE class to some allergens

-          these IgE antibodies bind to mast cells

-          this is sensitization

-          if allergen is encountered again, IgE binds allergen and stimulates mast cell to dump histamines and other molecules

o   these cause blood vessel dilation, smooth muscle contraction and mucus producing cells to secrete

o   in asthma the reaction is localized to air passages – smooth muscle contractions makes breathing difficult

o   in anaphylactic shock the blood vessels dilate so rapidly and so much that blood pressure drops. Smooth muscle contracts, can lead to death