Somatic hypermutation and design and chance

Somatic hypermutation is an amazing process which increases the diversity of the antibody response and can also lead to an increase in antibody affinity over time. As we noted in lecture, the human body has the potential to make 10 billion different antibodies from just a few gene regions and somatic hypermutation helps increase this diversity.

Somatic hypermutation is a process which essentially involves specific but semi-random mutation events which are focused only on a small region of the antibody genes.  The small region just happens to be the binding site of antibodies for foreign antigens.

 Mutations at large in the genome are often deleterious, yet somatic hypermutation and a process of selection leads to positive benefit for the host.  Thus, from a design perspective we cannot say that all mutations or natural selection processes are neutral or bad or deleterious.



But from a design perspective, why use a mutation process to increase antibody diversity and affinity?

What are some of the advantages involved in using a mutation system to increase immune function in this way?

Due Nov 24

Thermosensing RNA and immune avoidance

 

 

 

Commensual bacteria are a normal part of the human body and its tissues. Many commensual bacteria have components which can activate the immune system but they  also express  mechanisms to mute that activation.  One interesting commensual that can cause serious disease is Neisseria meningitis. However this commensual is also found in many individuals as part of the normal flora and can use factor H and other strategies to "hide out." 

 

Recently, it has been discovered that Neisseria meningitis can be activated to cause inflammation during host infection with influenza or other respiratory pathogens.  It is activated via RNA thermosensors. RNA thermosensors are stretches of double stranded RNA  that "melt" during high temperatures associated with fever.  This melted RNA then can be used to make proteins etc...that may induce virulence.  This is a fascinating response.

 

Since some microbiologists believe that normal flora bacteria were designed to be part of the human body, what role could these thermosensors play other than promoting virulence?

 

 

Do some research and find out more about how Neisseria meningitis  hides out and evades the immune system and also come up with a theory that might explain its RNA thermosensor activation during viral infection.

 

 

DUE NOV10

Hope for an AIDS Vaccine and bNAbs

Research on an AIDS vaccine has been ongoing for years. Very few positive results have been achieved. More recently the focus has been on broadly neutralizing antibodies (bNAbs). Broadly neutralizing antibodies show up naturally in a person infected with HIV only later in the infection. These antibodies have been shown to be effective in neutralizing the HIV virus but only if they appear early in HIV infection.

The idea now is to try to develop a vaccine which elicits bNAbs.

In your investigation of this problem, determine why the vaccines developed in the past have largely been ineffective in prevening AIDS.

Also, answer the following questions.

Why are bNAbs effective?
Why are they more effective in early infection?
Why are they produced later in HIV infection?
Do you think an effective AIDS vaccine will be developed?
Could bNAbs be isolated and purified and used in a passive vaccine?

due Oct 20

The mammalian immune system appears to be the most complex of all known animal and plant immune systems. In fact, invertebrates do not possess in general most aspects and the adaptive immune system. Some creatures like fish possess some antibodies but not the full repertoire of antibodies and other factors found in mammalian systems....thus fish appear to possess a "transitional" immune system.

Mammals and humans require the adaptive immune system for survival. And even though invertebrates don't appear to require the adaptive system for survival they do display some immune responses consistent with the adaptive immune response...i.e, rejection of transplanted tissue. More recently, jawless fish do display lymphocyte type cells, consistent with an adaptive system. Is this evidence of an intermediate system? 

 

Discuss the evolution and design aspects of the immune systems found in plants, invertebrates, mammals and fish. Do fish really possess a "transitional" immune system? Do any truly "intermediate" adaptive immune systems exist? Do you see design features inherent in the invertebrate immune system which appears to function without an adaptive system?

DUE Sept 26

Vaccine controversy

The history of Immunology largely involves the discovery of vaccines. Vaccines have undoubtedly saved millions of lives over the decades they have been used. However vaccines are not without controversy. Many people think that there is link between vaccines and autism.  There are some families that do not get vaccinated. There is some evidence that vaccines have caused the disease they are trying to prevent as in the recent case of polio vaccines..this is called VDPV..vaccine derived polioviruses.

Do some research and examine the evidence.  Do you think there is a link between autism and vaccine use?

Check out the VDPV cases. Have there been deaths in this case? How many cases of vaccine induced polio have been documented?  Is there enough evidence in this case to make all vaccine's suspect as dangerous?

Would you or will you have your children vaccinated?

Do you think polio can be eradicated?

Blog responses are due Sept 9