This web page was produced as an assignment for an undergraduate course at Davidson College.
Immunological Responses
Innate Immunity
The Innate immunological system is the first line of defense against anitbodies and invaders in a non-specific matter. The cells and organisms that are released to attack the invader recognize the antigen in a generic way and are unable to develop memory or protective immunity to the host. Innate immunity calls on cells to the site of infection and inflammation, it activates the complement cascade, IDs and removes foreign substances with specialized T cells, and through antigen presenting cells activates the adaptive immune system. Mast cells, phagocytes, macrophages, neutrophils, dendritic cells, basophils, and natural killer cells are all a part of innate immunity and help get rid of antigen present within the body.
The first symptoms that come with syphilis are the reactions to that of the initial infection. Redness, irritation, sores, inflammation are all responses of the immune system trying to fight the pathogen. However, this system does not have long term effects allowing for the pathogen to slip through the cracks. Much of the symptoms that come from the initial detection of syphilis are produced by the innate immune system. Syphilis can enter deeper tissues and into the bloodstream by passing through the connections between endothelial cells. Syphilis induces the production of matrix metalloproteinase-1 (MMP-1). MMP-1 is used in the process of breaking the collagen form down, which may give insight in how Syphilis can penetrate tissues. Syphilis as a pathogen signals inflammatory and immune cells to travel from the blood stream to the site of infection to help combat its presence. Syphilis activates many adhesion molecules (ICAM-1, VCAM-1, E-selectin) which may promote the idea that endothelial cell activation is an antigen-specific, active process. These can only be activated by specific syphilis molecules. Ingested pathogens within the body are then presented to phagocytes to be destroyed, usually recognized by endothelial cells, dendritic cells, and macrophages. Specialized dendrtic cells are stimulated and found in lesions of the skin during primary and secondary syphilis. Dendritic cells can also be found in the mucosa, the intestinal wall, and the heart where syphilis can at times infect. Dendritic cells can often ingest pathogens and present them to T cells in the lymph nodes and also can produce inflammatory cytokines in response to pathogenic infection. Syphilis can delay the maturation of Dendritic cells which in turn delays the inflammatory response, allowing syphilis molecules to enter the skin and deep inside organs and tissue.
Hummoral Immunity
The Hummoral immunological system is controlled by secreted antibodies produced by B cells. These secreted antibodies will bind to the surface of antigen and basically makes them a target for destruction. The humoral response also brings about Th2 activation, cytokine production, germinal center formation, affinity maturation, and memory cell generation. Through B cell, Antigen Presenting Cell and T cell recognition, this entire process will eventually bring about the secretion of antibodies against the antigen that is present within the body.
With the membrane exposed protein on the antigen's surface it makes it extremely difficult for cells to recognize and present the syphilis antigen to other cells to develop an immunological response towards the foreign invader. However, IgM and IgG antibodies are present within the body within six days of initial infection. Specific IgM is continually produced continually stimulating B cells after exposure to the syphilis antigen. IgG has also been found in latent stages of syphilis. The antibody response produced during infection is specific for a borad range of syphilis molecules. Antibodies help with the neutralization of dermal lesions, however discontinuing antibody administration can create reoccurance of lesions near the innoculation site within days. Unfortunately, antibody alone can only inhibit lesion development and not kill and prevent syphilis infection.
Cellular Immunity
The Cellular immunological system protects the body by activating antigen-specific cytotoxic T cells, macrophages, natural killer cells, and stimulates cells to release cytokines to help induce other helpful mechanisms and tasks of other cells that are involved with adaptive and innate immunity. Cellular immunity is most effective at removing virus-infected cells.
Dendritic cells present specific antigens to T cells in the lymph nodes which cause stimulation and differentiation among cells, allowing them to travel to the site of infection and perform their specialized functions. T cells are highly reactive to syphilis protein and are detectable within three days on initial infection. Macrophages follow T cells shortly after within several days, causing the detection of syphilis organisms to exponentially digressing. Helper T cells and cytolytic T cells (CD4+/CD8+) and macrophages can be found in chancres and secondary lesions after intial infection. Studies have shown that the presence of CD4+ cells can actually be macrophages expressing the CD4 receptor. Opsonizing agents help mark the antigen for expression to help immune cells find and destroy the invader.
Evasion of Pathogen
Evasion of a pathogen can be very tricky but is easier than you think. Althering the proteins on the membrane or altering your structure can automatically help in evading the immune system. Syphilis actually has a membrane-exposed protein that virtually makes it invisible to the immune system. This is what allows syphilis to live in the host for so long without treatment. As of right now, scientists are looking for a way to create a vaccine for syphilis that will block this membrane protein and help the immune system find the invader and destroy it. Therefore, the innate immune response will initially through everything it has at the bacteria but the evasion techniques of syphilis makes it hard for the adaptive immune system to produce "immunity" towards syphilis and even harder for the innate immune response to regualte the syphilis antigen.
The syphilis pathogen can invade areas of the body that are known as "immune privileged" which have less surveillance by the innate immune system. Those syphilis organisms that have survived within these "immune privileged" sites can then replicate and eventually infect surrounding tissue. Syphilis can also slow down its metabolism and exploit this mechanism to go unnoticed. The syphilis organisms can maintain infection with minimal syphilis cells, dividing very slowly, and essentially become invisible to the immune system. Syphilis can become undetectable in a period from months to years through this slow division process. Pathogens usually aquire iron for uptake from the host to help growth processes, therefore once the pathogen is detected the host can initiate iron binding proteins to limit the pathogen's interaction. Syphilis on the other hand has found a way to by-pass this effect and can uptake other types of metals found in host proteins, and does not need iron because it lacks an electron transport chain.
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Any questions, comments, or concerns please email at stdouglass@davidson.edu