Immune responses to vaccines: innate immunity

After spending most of the weekend working in my garden, I spent today relaxing, barbequing, and spending time with my family.

Andrew and my garden

Right to left: Andrew, his Grandpa Esvelt, and his Uncle Seth

I don't know about you, but I remember very little about the human immune system from grade school and high school. I remember that white blood cells eat (phagocytize) bad stuff and I remember Raquel Welch being attacked by antibodies in The Fantastic Voyage (Maybe you're not that old).



Phagocytosis

Of course, I learned more about the immune system in nursing school and in my postgraduate curriculum. A lot of what I've learned about the immune system is from my reading about the pathology and pathophysiology of malaria. Like a lot of other diseases, many of the symptoms of malaria are caused by immune responses to the infection. As I mentioned in my post on hepatitis, hepatotropic viruses themselves do not damage the liver. The damage is caused by immune responses that kill infected liver cells.

The immune system is much more complex than phagocytic leukocytes (Greek: phagō, to eat; leukos, white; kytos-, cell) and Raquel Welch. In fact, immunity is mediated through several systems that work together. White blood cells not only eat invading pathogens and secrete antibodies, they also produce chemical messengers like interleukins that mediate inflammation and other cytokines that mobilize other white blood cells. There are also dozens of different types and subtypes of white blood cells that perform different functions.

There is no way I can adequately discuss all of the intricacies of the subject of medical textbooks. My purpose is to introduce some of the major players in immune responses to diseases and vaccines. I started writing this several weeks ago and got bogged down in too many details, so I'm going to start with innate immunity and save adaptive immunity, that is, why we give vaccines in the first place, for a later post.

Self versus non-self

The first priority of the immune system is recognizing "self" from "non-self," that is, anything that isn't part of our bodies. There are molecules on the surface of cells that are used by the different components of the immune system to identify those cells as self. Likewise, there are molecules on the surfaces of pathogenic organisms that the components of the immune system recognize are non-self. Cells that are infected with certain pathogens will place those molecules on their surface to target themselves to be killed to prevent other cells from being infected.

Innate immunity

Innate immunity refers to non-specific mechanisms the body uses to protect itself from infection. Skin, mucous membranes, and stomach acid are barriers that prevent pathogenic organisms from entering the body. Complement is a system of proteins that, among other things, tears holes in cells that are not recognized as self. The aptly-named natural killer cells (NK) kill cells that are infected with viruses and some type of tumor cells.

Phagocytic cells like macrophages ("big eaters") and dendritic cells are antigen-presenting cells (APCs). They are part of the innate immune system, but they perform an essential function in mobilizing adaptive immune responses. Most cells use major histocompatibility complex (MHC) molecules to "present" part of proteins found inside of the cell on its surface. It allows specialized white blood cells to "see" what's happening inside of the cell. MCH proteins on cell infected with viruses present viral antigens on the cell surface. This allows NK cells and cytotoxic lymphocytes (CTL) to target the cell for destruction. Antigen presenting cells use MHC molecules to present proteins to white blood cells that are part of the adaptive immune system.

Inflammation is another innate response to injury or infection that stimulates adaptive immune responses.

Antigens are foreign substances that cause antibody response. Allergens are a type of antigen. An antigen may have several epitopes, which are areas on the molecule to which antibodies can attach. For example, an influenza virus has several antigens on its surface including hemagglutinin, neuraminidase, and M2 ion channel. Influenza vaccines use epitopes or "antigenic sites" of the hemagglutinin head to stimulate production of antibodies that will attach to that part of the virus. Unfortunately, the hemagglutinin head changes shape (antigenic drift) so that antibodies to those epitopes will not bind to the antigen. Some researchers have suggested using epitopes on the hemagglutinin stalk or on the M2 ion channel as vaccine antigens.

 

CDC, 2014

 

Next: adaptive immunity.

References 

Kroger, A. T., Pickering, L. K., Wharton, M., Mawle, A., Hinman, A. R., & Orenstein, W. A. (2015). Immunization. In J. E. Bennett, R. Dolin, & M. J. Blaser (Eds.) Mandell, Douglas, and Bennett's principles and practice of infectious diseases, 8th ed. [Electronic version]. Saunders.

 

Pickering, L. K & Orenstein, W. O. (2012). Active immunization. In S. S. Long, L. K. Pickering, & C. G. Prober (Eds.) Principles and practice of pediatric infectious diseases, 4th ed. [Electronic version]. Elsevier.

 

Playfair, J. H. L., & Chain, B. M. (2005). Immunology at a glance, 8th ed. Malden, MA: Blackwell Science.

 

Siegrist, C-A. (2013). Vaccine immunology. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds.) Vaccines, 6th ed. [Electronic version]. Saunders.

 

Sompayrac, L. (2003) How the immune system works, 2nd ed. Malden, MA: Blackwell Science.