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Herd Immunity

In MicroBiology class we’re still a long way from our immunology unit, but we have started talking about some basic principles of the immunity and vaccination, including the idea of ‘herd immunity’. This is the notion that even incomplete vaccination may be sufficient to prevent the spread of an infection through an entire population.

In this video, Scientific American’s Dina Fine Maron explains Herd Immunity very simply.

http://link.brightcove.com/services/player/bcpid910142956001?bckey=AQ~~,AAAAAFNl7zk~,OmXvgxJOvrGd04F7pX4DjTcq0KXtMvCb&bctid=2632175457001

Interestingly, as I started writing this, I stumbled upon the old crap movie, Outbreak – I’ll also be calling this film crap on my film blog, 100FilmIn100Days.

 
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Posted by on August 31, 2013 in Uncategorized

 

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A quick description of Lymphocyte Development and Activation

Lymphocytes Development and Activation

Lymphocytes (B cells and T cells – we’ll not talk about NK cells here) go through a generalizable sequence of maturation events. Each starts in the Bone Marrow (BM) as a Hematopoietic Stem Cell (HSC), where it starts its development. T cells leave the BM relatively sooner and go to the Thymus, while B cells remain in the BM for most of their development and then finalize development in the spleen.

 Positive Selection for BCR/TCR Development

Regardless of the type of cell (T or B), development occurs in two stages – First, each cell will attempt to make a unique lymphoid receptor (B cells have a BCR; T cells have a TCR). In order to do this, genetic material must be shuffled. While this shuffling does randomize the binding pocket of the lymphoid receptor, it may also destabilize these same receptors’ structure. To account for this, lymphocytes undergo a ‘positive selection’ period that ensures that a viable receptor is formed. This is actually done twice: once to ensure that a ‘Pre-Lymphoid Receptor’ is formed and again to for a ‘Mature Receptor.’  However, both are considered positive selection. Failure to pass this selection point leads to death of the cell. (In the figure below, Pre-Lymphocyte receptors are colored red, mature receptors are grey)

Negative Selection Against Self-Reactive BCR/ TCRs

Once cells have survived positive selection, they are considered Immature Lymphocytes. Although the terminology is poor here, these immature cells have mature lymphocyte receptors. At this point, these receptors have to be tested against all possible ‘Self ‘- antigens. In this case, binding means that these cells have the potential to react against the self – this is a no, no. The Immune System turned against the self is extraordinarily dangerous. Therefore, self-reactive cells are eliminated during this negative selection process. (In the figure below, mature lymphocytes have grey nucleus, all prior stages have red nuclei).

LymphosFollowing these developmental stages, the cells that have survived both positive and negative selection are 1) stable, mature lymphocyte receptors and 2) not reactive to ‘self’. These cells then enter the immune repertoire for that organism and are available to react against any foreign threats. Again, it is important to emphasize that each lymphocyte has a unique receptor and therefore will only get activated by a unique foreign antigen.

I may write more later to discuss some of the details that distinguish B and T cell development, but for now, this generalizable description will suffice.

Clonal Selection

Once a part of the immune repertoire, lymphocytes are on the lookout for foreign antigen that is capable of being bound by that cell’s receptor. Depending on the cell type, this interaction may be in one of several contexts (either in the context of MHC I, MHC II or as a naïve, soluble antigen), but regardless of the context, these ‘naïve’ lymphocytes will become activated by binding of their lymphocyte receptor. And once activated, lymphocytes will proliferate and differentiate. Differentiation typically goes in one of two general directions:

1)   generating activated effector cells (these secrete antibody if B cells, kill target cells, if CD8 T cells, or become helpers if CD4 T cells)

–or-

2)   generating memory cells, cells that act the same as the mature naïve cell that was activated, but are more numerous and can, themselves be activated upon stimulation.

An example of this activation is shown below in this HHMI video about how CD8 T cells can be stimulated to activate and then kill any target cells. This video also does a good job of illustrating how antigens get digested within a cell and expressed in the context of MHC I.

http://www.hhmi.org/biointeractive/media/antigen_ctl-lg.mov

 
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Posted by on April 25, 2013 in Uncategorized

 

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Complement – an antibody-guided innate immune response

That’s a complicated title. What it means is that complement is part of out innate immune response, i.e. it is pre-made, ready-to-go and does not adapt over time in response to immune challenges. However, it is guided by antibodies, which are part of the adaptive immune response.

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This bad guy, invading cell, has been opsonized by antibodies – they bind all over the cell 1)preventing it from binding other host cells and 2)recruiting complement and immune cells.

What complement is, is a number of proteins that come together and activate one another in a cascade that coordinates the formation of a hole- or pore- through the membrane of foreign cells. The cascade begins when the first of the complement proteins associates with antibodies that are opsonizing a foreign cell.

Once recruited, complement proteins will activate in a cascade (see movie) in which small parts of the proteins break off and act as anaphylatoxins recruiting and activating  immune cells to the region. Meanwhile, the larger protein elements will assemble into pore-forming complexes that will kill the invading cell.

With this in mind, watch the animation below looking for:

1) antibodies binding to foreign cells

2) early complement proteins being recruited

3) complement breaking into large and small proteins

4) the smaller ones floating away to recruit immune cells

5) the larger ones forming membrane pores and killing the invading cell.

(don’t worry about the sequence of events or the specific proteins involved)

 
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Posted by on April 11, 2013 in Uncategorized

 

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Cancer and the immune system (briefly)

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Macrophage engulfing bacteria

 What a breath of fresh air! A good old friend of mine, who I met while in graduate school and is now living in Mexico city has been working on a couple of papers that he is submitting to some English language journals. I’ve only read one of them so far – it’s an interesting review of work that suggests that tumors actively co-opt processes of the immune system to their own advantage. His spoken English is quite good, but it’s another thing altogether to write well for a scientific publication. Lucky for me, I guess, because it gives me a way to be involved.

It is well established that the immune system functions to prevent tumor formation known as immunosurveillance. This is pretty consistent with the basic role of defending the self against any non-self target it encounters. If you’re unfamiliar with immunology and want one thing to learn, that’s it: The immune system is there to recognize a black and white world of self vs non-self. The details are complicated, but it’s fairly well worked out that through a series of positive and negative selection events you can train your immune cells to be tolerant of you (self), but reactive against anything new (non-self).

With respect to cancer, it’s important to recognize that these cells start out as self and are ignored by the immune system, but they change in a way that they are not acting the way they should. The problem for the immune system is that these changes typically just mean that the cells are acting abnormally, but they don’t necessarily look foreign. Despite this, we know that animals that lack a functional immune system will succumb to tumors at higher frequency earlier in life than those with competent immunity.

My friend’s article extends this relationship beyond immunosurvellience and suggests that the tumor cells undergo a selection process by the immune system that will eliminate weaker cells, leaving only cells that either escape the notice of the immune system entirely or are extraordinarily resistant to attacks. Further, he describes that the remaining cells will often co-opt signals of the immune system to advance their own function and survival. 

I look forward to finishing up this paper and hope to be able to point you toward a journal that it is published in sometime in the near future. Until then, it’s so refreshing to think about immunology again. I miss it.

 

 
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Posted by on November 3, 2012 in Uncategorized

 

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This week in General Bio

This week we are studying the cell.

We have already discussed the importance of the cell in defining life (The Cell Theory) and talked about why this is a meaningful definition of life. I also spent a little time discussing viruses and how they defy this definition, but are often included or excluded depending upon the view or purpose of the investigator / student. (i.e. Viruses fail to be alive if the Cell Theory is used as the definition, but they are often considered alive by microbiologists for the purpose of classification, discussion of evolution, etc).

We began by recalling when in history people first realized that there was a microscopic world existing at all. This led into a talk about classification and how life falls into two major groups of cells, Prokaryotic and Eukaryotic. There are a number of key differences between these types of  cells, but I focus on just a few: 

1. Prokaryotic cells tend to be smaller

2. Prokaryotic cells have closed circles of DNA, Eukaryotic cells have linear chromosomes

3. Prokaryotic and Eukaryotic ribosomes are different from one another

4. Prokaryotic cells lack membrane-bound organelles (most notably, the nucleus)

We discussed other features, but I think these are the hallmark differences. Prokaryotic cells span two domains of life, the bacteria (which I tend to focus on) and the archae (which are more ancient and often extremophiles). Eukaryotic cells fall into four kingdoms: animalia, plantae, fungi and protista. With a quick discussion about some differences between these groups, I shelved all but animals and said that this was the group we would focus on for the remainder of the semester (with some exceptions such as photosynthesis).

What makes these four kingdoms similar is their Eukaryotic cell type. As I stated above, one feature of Eukaryotic cells is their membrane-bound organelles. These organelles are how the cell divies up its many tasks into separate functions and gets each of them done by some specific structure. In addition to discussing true organelles, we also discussed other structures and their functions (Ribosomes, plasma membranes, cytoplasm, cytoskeleton)

We finished up Tuesday’s class after just introducing all of the players. Today we will be putting some of them together to show how they function as parts of a larger organization. The three things I have in mind to walk through are: 

1. Energy Pathway – how solar energy gets converted into chemical energy, how that energy is stored (not getting into this part much) and then how that energy is brought back out and converted into a more usable form (ATP) that is put to work to make cells do things.

2. The Central Dogma – fleshed out this time with names of some of the processes. Initially focusing on how information is transformed into something that can actually do work (proteins). Then discussing how these proteins are made in a little more detail (cytoplasmic vs secretory proteins). This lets us talk about the ER, Golgi, Ribosomes and even ends with exocytosis.

3. Phagocytosis – I’m an immunologist, so I think about how macrophages attack cells and other foreign particles all the time. This is a good way to reverse the process of exocytosis and talk about endocytosis. Following endocytosis, we can then bring lysosomes and peroxisomes into play and discuss how they function to break down these ‘non-self’ items so that they become harmless (I’ll end by quickly tying this into the immune system’s antigen display mechanism – but without any detail).

That may be enough for them today. Depending upon questions, things can either go much quicker or drag out for the balance of the class. I expect that we will finish this material with enough time to at least get started with the next chapter – membranes. I like this chapter anyway and I think it’s the chapter that puts the students into the ‘mind’ of the cell the best. If you focus on a membrane and how it handles transport and diffusion, you are zoomed in so close, that suddenly, the cell feels large and familiar.

Lastly, I am really hoping to find an great animation of cellular processes that made the email loop of Penn a couple years ago. Cross your fingers – I have no idea where I might get a copy.

 
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Posted by on September 6, 2012 in Uncategorized

 

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