Chapter 8 - Immune Response Against Viruses

 

I. First line of defense - non specific natural barriers

 

II. Second line of defense - macrophages and reticuloendothelial system (RES)

A. macrophages are found in all parts of body and recognize foreign antigens

B. reticuloendothelial system includes cells of lymph system and macrophages

C. macrophages are particularly important because not only are they first line of defense, they are notoriously susceptible to infection by viruses. So they can be the means of viral eradication, but they also can be the means of virus dissemination throughout the body.

D. macrophages are also important in processing of viruses to be presented to B-cells and T-cells for antibody production (antigen presentation)

 

III. Third line of defense - specific immunity.

1. The basis of specific immunity - primary and secondary (anamnestic) immune response

 

2. The beginnings of the immune response - antigen recognition

a. The basis of this is clonal selection (McFarlane Burnett). We have cells circulating in our system that are capable of responding to approximately 1,000,000 different antigens. However, there are only a few of them, not enough to mount a large response. When an antigen is encountered, the cells that do the encountering are stimulated into blastogenesis (rapid replication) and make many more coplies of themself. Now, instead of a platoon of cells, there is an army (clonal expansion) that is primed (stimulated) to respond to the invading antigen. These cells often recruit other cells via cytokines to participate in the response.

b. There are 4 basic types of which 2 are the most important (Figure 8-1 in book)

  • An antigen presenting cell, such as a macrophage destroys the virus (disassembles it) and in the process viral protein associates with a MHCII peptide that migrates to the surface of the cell. The viral protein sits in a small groove in the MHCII peptide. Receptors on Th and Td cells (CD4+) recognize the MHCII and associate with it. Another receptor on the T cell recognizes and responds to the antigen that is in the groove. The response results in production of antibody, cytotoxic T cells, and inflammation (rubror, calor, dolor, tumor)
  • An infected cells has a viral protein (which is being produced) associate with a MHCI receptor and the complex migrates to the cell surface. Tc and NK cells have CD8+ receptors that recognize the MHCI. They also have other receptors that recognize the antigen and mount a response. The response results in immune cytolysis of infected cells.
  • Free viruses can be recognized by B-cells and antibody is made.
  • Infected cells that have viral antigens on their membrane can be recognized by circulating antibody (IgG) and this complex is then recognized by K (killer) cells.

c. The different arms of the immune response (Figure 8-4)

  • neutralization of virus by macrophages + antibody
  • neutralization of virus by macrophages without the aid of antibody
  • destruction of virus-infected cells by macrophages + antibody
  • production of interferon by macrophages and Td cells (interference with viral replication)
  • neutralization and clearing of virus by serum IgG or mucosal IgA
  • destruction of infect cells by antibody-dependent complement-mediated cytolysis (ADCM)
  • destruction of infected cells by K cells with the help of antibody
  • destruction of infected cells by NK cells with the aid of interferon (cytokine recruitment)
  • destruction of infected cells by cytotoxic T cells (Tc) (immune cytolysis)