Lecture #14: The Immune Response and AIDs
I. THE HUMORAL RESPONSE
1. The humoral response occurs when B-cells with specific receptors are stimulated by an antigen to differentiate into a clone of plasma cells that secrete specific antibodies.
2. Activation of a B-cell to form a clone of plasma cells can occur by either of two mechanisms:
a. Mechanism One (simple): (Fig 43.6) (mainly against bacteria)
(1) there are millions of B-cells, with about 100,000 receptors on their membranes.
(2) the receptors have properties of different antibodies.
(3) the binding of antigen to specific receptors on the surface of the B-cell.
(4) sometimes, this action alone will stimulate B-cells to become plasma cells and produce specific antibodies that are released into the blood.
(5) this B-cell response is stimulated by polysaccharides and proteins on bacteria.
(6) a secondary immune response to the same antigen is amplified. (Fig. 43.7)
b. Mechanism Two (more complex):
(More commonly than in step one, macrophages and helper T-cells are required.)
PRELIMINARY NOTE: About (MHC) molecules. (Fig 43.9)
(a) Cytotoxic T-cells interact with Class I MHC on antigen-presenting infected body cells.
(b) Helper T-cells interact with Class II mHC on antigen-presenting macrophages.
(1) macrophages phagocytoze virus with antigens. (Fig. 43.13)
(2) partially digested antigen molecules are displayed in association with class II MHC molecules imbedded in plasma membrane of macrophage (now called an antigen-presenting cell).
(3) a helper T-cell recognizes this self/nonself complex on surface of the macrophage and binds to it.
(4) this contact between macrophage and helper T-cell stimulates the T-cell to form clones of T-cells keyed to the specific antigen.
(5) by the same mechanism, the helper T-cells recognize the complementary B-cells displaying the same antigen.
(6) the helper T-cell begins producing cytokines that promote division of B-cells.
(7) this interaction activates the B-cell to develop into an antibody-secreting plasma cell.
(8) plasma cells secrete as many as 2000 antibody molecules/sec for their 4-5 days of existence. (2,000 molecules X 86,400 sec X 5 days = 864 million molecules)
II. THE CELL-MEDIATED RESPONSE
1. Helper T-cell/macrophage interaction vs Cytotoxic T-cell/infected cell interaction:
a. Helper T-cell/macrophage interaction: (Fig. 43.11)
This is basically the same as the humoral response except that we add that:
(1) binding of the helper T-cell to an antigen-presenting macrophage causes the macrophage to secrete a cytokine called interleukin-1. (cytokines are molecules secreted by one cell to regulate neighboring cells.)
(2) interleukin-1 stimulates the helper T-cell and causes it to secrete IL-2.
(3) IL-2 stimulates cloning of helper T-cells and helps activate B-cells, thus stimulating the humoral response against a specific antigen.
(4) IL-2 also stimulates differentiation of cytotoxic T-cells for cell-mediated response (to begin looking for body cells other than macrophages infected.
b. Cytotoxic T-cell/infected cell interaction: (Fig 43.12)
(1) cytotoxic T-cells recognize specific antigens presented by infected body cells in association with the class I MHC markers. (MHCII are only on macrophages, B-cells, and some T-cells.)
(2) when the cytotoxic T-cell "docks" on the surface of an infected body cell, it releases perforin, a protein that forms a membrane lesion on the infected cell.
(3) the infected body cell loses cytoplasm through the lesion and undergoes lysis.
(4) cytotoxic T-cells do basically the same thing to many cancer cells which also express "foreign" antigens on their surface.
III. DISORDERS OF THE IMMUNE SYSTEM
1. Autoimmune diseases occur when there is development of immune reactions against normal components (e.g., nucleic acids) of one's own body (leading to arthritic and inflammatory diseases).
2. Allergies occur when IgE molecules (on mast cells) bind to antigens (allergens) causing degranulation of mast cells and a flood of histamine and mediators of inflammation. (Fig. 43.18)
3. Acquired Immune Deficiency Syndrome
(AIDS) (Fig. 18.7)
a. caused by the human immunodeficiency virus (HIV) and is 100% lethal.
b. HIV first recognized in 1983, but blood dating back to 1959 contains the virus.
c. HIV infects certain T-cells, including helper T-cells, that have a membrane receptor called CD4).
d. a glycoprotein called gp120 on the HIV virus binds to the CD4.
e. CD4 is also on some macrophages, and a few B-cells, which can be infected.
f. following attachment, the virus enters the cell and produces reverse transcriptase.
g. thus, the HIV virus is a retrovirus.
h. the immune system responds effectively against HIV infection at first.
i. however, the HIV undergoes extremely rapid mutational changes, and evades existing antibodies.
j. in addition, when infected helper T-cells are called into duty, they produce more HIV, rather than the needed antibody.
k. eventually, the immune cells are overwhelmed by the accumulation of resistant viruses.
l. in the weakened state, the AIDS syndrome sets in and the infected individual becomes more and more susceptible to:
(1) Kaposi's sarcoma, a cancer of the skin and blood vessels, and
(2) Pneumocystis pneumonia, a respiratory infection caused by a protozoan.
m. Summary of the stages of an HIV infection (Fig. 43.20)
(1) 26% of the adults in Zimbabwe are infected with HIV.
(2) this crisis will result in 600,000 new orphans this year.