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Systemic lupus erythematosus is an autoimmune disease in which the body's immune system attacks healthy cells. How exactly do B and T cells attack these cells they mistake for pathogens?
The initial trigger for the disease is unknown and can be different from person to person. However, we do know that there can be environmental or infectious triggers that are further potentiated by genetic and hormonal factors.
The pathology of SLE is associated with the development of "auto-antibodies" or "anti-nuclear antibodies," so saying that B cells and T cells attack healthy cells is not exactly correct - More accurately they produce antibodies against proteins on healthy cells, which form immune complexes, activate complement and induce apoptosis. To produce auto-antibodies, events occur as follows:
- The trigger causes macrophages or antigen-presenting cells (APCs) to display self- or auto-antigens
- APCs recruit B cells to start producing antibodies against the antigen
- APCs activate T helper cells, which stimulate inflammation and perpetually activate the B cells to produce auto-antibodies
The following immune abnormalities are associated with SLE (particular focus on B cells and T cells)
- High levels of circulating B cells
- Decreased levels of T suppressor cells, which would otherwise regulate the immune system and auto-antibody production
- Abnormal B cell signalling and persistent activation of B cells (IL-6, IL-10)
- Prolonged life span of B cells, possibly due to poor immunoregulation (#2)
Reference: Schur PH, Hahn BH, Pisetsky DS, Ramirez Curtis M. Epidemiology and pathogenesis of systemic lupus erythematosus. Up to date. Topic last updated: Feb 5 2016. Subscription access only.
Immune System: Diseases, Disorders & Function
The role of the immune system — a collection of structures and processes within the body — is to protect against disease or other potentially damaging foreign bodies. When functioning properly, the immune system identifies a variety of threats, including viruses, bacteria and parasites, and distinguishes them from the body's own healthy tissue, according to Merck Manuals.
B cells develop from hematopoietic stem cells (HSCs) that originate from bone marrow.   HSCs first differentiate into multipotent progenitor (MPP) cells, then common lymphoid progenitor (CLP) cells.  From here, their development into B cells occurs in several stages (shown in image to the right), each marked by various gene expression patterns and immunoglobulin H chain and L chain gene loci arrangements, the latter due to B cells undergoing V(D)J recombination as they develop. 
B cells undergo two types of selection while developing in the bone marrow to ensure proper development, both involving B cell receptors (BCR) on the surface of the cell. Positive selection occurs through antigen-independent signaling involving both the pre-BCR and the BCR.   If these receptors do not bind to their ligand, B cells do not receive the proper signals and cease to develop.   Negative selection occurs through the binding of self-antigen with the BCR If the BCR can bind strongly to self-antigen, then the B cell undergoes one of four fates: clonal deletion, receptor editing, anergy, or ignorance (B cell ignores signal and continues development).  This negative selection process leads to a state of central tolerance, in which the mature B cells do not bind self antigens present in the bone marrow. 
To complete development, immature B cells migrate from the bone marrow into the spleen as transitional B cells, passing through two transitional stages: T1 and T2.  Throughout their migration to the spleen and after spleen entry, they are considered T1 B cells.  Within the spleen, T1 B cells transition to T2 B cells.  T2 B cells differentiate into either follicular (FO) B cells or marginal zone (MZ) B cells depending on signals received through the BCR and other receptors.  Once differentiated, they are now considered mature B cells, or naive B cells. 
B cell activation occurs in the secondary lymphoid organs (SLOs), such as the spleen and lymph nodes.  After B cells mature in the bone marrow, they migrate through the blood to SLOs, which receive a constant supply of antigen through circulating lymph.  At the SLO, B cell activation begins when the B cell binds to an antigen via its BCR.  Although the events taking place immediately after activation have yet to be completely determined, it is believed that B cells are activated in accordance with the kinetic segregation model [ citation needed ] , initially determined in T lymphocytes. This model denotes that before antigen stimulation, receptors diffuse through the membrane coming into contact with Lck and CD45 in equal frequency, rendering a net equilibrium of phosphorylation and non-phosphorylation. It is only when the cell comes in contact with an antigen presenting cell that the larger CD45 is displaced due to the close distance between the two membranes. This allows for net phosphorylation of the BCR and the initiation of the signal transduction pathway [ citation needed ] . Of the three B cell subsets, FO B cells preferentially undergo T cell-dependent activation while MZ B cells and B1 B cells preferentially undergo T cell-independent activation. 
B cell activation is enhanced through the activity of CD21, a surface receptor in complex with surface proteins CD19 and CD81 (all three are collectively known as the B cell coreceptor complex).  When a BCR binds an antigen tagged with a fragment of the C3 complement protein, CD21 binds the C3 fragment, co-ligates with the bound BCR, and signals are transduced through CD19 and CD81 to lower the activation threshold of the cell. 
T cell-dependent activation Edit
Antigens that activate B cells with the help of T-cell are known as T cell-dependent (TD) antigens and include foreign proteins.  They are named as such because they are unable to induce a humoral response in organisms that lack T cells.  B cell responses to these antigens takes multiple days, though antibodies generated have a higher affinity and are more functionally versatile than those generated from T cell-independent activation. 
Once a BCR binds a TD antigen, the antigen is taken up into the B cell through receptor-mediated endocytosis, degraded, and presented to T cells as peptide pieces in complex with MHC-II molecules on the cell membrane.  T helper (TH) cells, typically follicular T helper (TFH) cells recognize and bind these MHC-II-peptide complexes through their T cell receptor (TCR).  Following TCR-MHC-II-peptide binding, T cells express the surface protein CD40L as well as cytokines such as IL-4 and IL-21.  CD40L serves as a necessary co-stimulatory factor for B cell activation by binding the B cell surface receptor CD40, which promotes B cell proliferation, immunoglobulin class switching, and somatic hypermutation as well as sustains T cell growth and differentiation.  T cell-derived cytokines bound by B cell cytokine receptors also promote B cell proliferation, immunoglobulin class switching, and somatic hypermutation as well as guide differentiation.  After B cells receive these signals, they are considered activated. 
Once activated, B cells participate in a two-step differentiation process that yields both short-lived plasmablasts for immediate protection and long-lived plasma cells and memory B cells for persistent protection.  The first step, known as the extrafollicular response, occurs outside lymphoid follicles but still in the SLO.  During this step activated B cells proliferate, may undergo immunoglobulin class switching, and differentiate into plasmablasts that produce early, weak antibodies mostly of class IgM.  The second step consists of activated B cells entering a lymphoid follicle and forming a germinal center (GC), which is a specialized microenvironment where B cells undergo extensive proliferation, immunoglobulin class switching, and affinity maturation directed by somatic hypermutation.  These processes are facilitated by TFH cells within the GC and generate both high-affinity memory B cells and long-lived plasma cells.  Resultant plasma cells secrete large amounts of antibody and either stay within the SLO or, more preferentially, migrate to bone marrow. 
T cell-independent activation Edit
Antigens that activate B cells without T cell help are known as T cell-independent (TI) antigens  and include foreign polysaccharides and unmethylated CpG DNA.  They are named as such because they are able to induce a humoral response in organisms that lack T cells.  B cell response to these antigens is rapid, though antibodies generated tend to have lower affinity and are less functionally versatile than those generated from T cell-dependent activation. 
As with TD antigens, B cells activated by TI antigens need additional signals to complete activation, but instead of receiving them from T cells, they are provided either by recognition and binding of a common microbial constituent to toll-like receptors (TLRs) or by extensive crosslinking of BCRs to repeated epitopes on a bacterial cell.  B cells activated by TI antigens go on to proliferate outside lymphoid follicles but still in SLOs (GCs do not form), possibly undergo immunoglobulin class switching, and differentiate into short-lived plasmablasts that produce early, weak antibodies mostly of class IgM, but also some populations of long-lived plasma cells. 
Memory B cell activation Edit
Memory B cell activation begins with the detection and binding of their target antigen, which is shared by their parent B cell.  Some memory B cells can be activated without T cell help, such as certain virus-specific memory B cells, but others need T cell help.  Upon antigen binding, the memory B cell takes up the antigen through receptor-mediated endocytosis, degrades it, and presents it to T cells as peptide pieces in complex with MHC-II molecules on the cell membrane.  Memory T helper (TH) cells, typically memory follicular T helper (TFH) cells, that were derived from T cells activated with the same antigen recognize and bind these MHC-II-peptide complexes through their TCR.  Following TCR-MHC-II-peptide binding and the relay of other signals from the memory TFH cell, the memory B cell is activated and differentiates either into plasmablasts and plasma cells via an extrafollicular response or enter a germinal center reaction where they generate plasma cells and more memory B cells.   It is unclear whether the memory B cells undergo further affinity maturation within these secondary GCs. 
- Plasmablast – A short-lived, proliferating antibody-secreting cell arising from B cell differentiation.  Plasmablasts are generated early in an infection and their antibodies tend to have a weaker affinity towards their target antigen compared to plasma cell.  Plasmablasts can result from T cell-independent activation of B cells or the extrafollicular response from T cell-dependent activation of B cells.  – A long-lived, non-proliferating antibody-secreting cell arising from B cell differentiation.  There is evidence that B cells first differentiate into a plasmablast-like cell, then differentiate into a plasma cell.  Plasma cells are generated later in an infection and, compared to plasmablasts, have antibodies with a higher affinity towards their target antigen due to affinity maturation in the germinal center (GC) and produce more antibodies.  Plasma cells typically result from the germinal center reaction from T cell-dependent activation of B cells, however they can also result from T cell-independent activation of B cells. 
- Lymphoplasmacytoid cell – A cell with a mixture of B lymphocyte and plasma cell morphological features that is thought to be closely related to or a subtype of plasma cells. This cell type is found in pre-malignant and malignant plasma cell dyscrasias that are associated with the secretion of IgM monoclonal proteins these dyscrasias include IgM monoclonal gammopathy of undetermined significance and Waldenström's macroglobulinemia.  – Dormant B cell arising from B cell differentiation.  Their function is to circulate through the body and initiate a stronger, more rapid antibody response (known as the anamnestic secondary antibody response) if they detect the antigen that had activated their parent B cell (memory B cells and their parent B cells share the same BCR, thus they detect the same antigen).  Memory B cells can be generated from T cell-dependent activation through both the extrafollicular response and the germinal center reaction as well as from T cell-independent activation of B1 cells. 
- B-2 cell – FO B cells and MZ B cells. 
- (also known as a B-2 cell) – Most common type of B cell and, when not circulating through the blood, is found mainly in the lymphoid follicles of secondary lymphoid organs (SLOs).  They are responsible for generating the majority of high-affinity antibodies during an infection.  – Found mainly in the marginal zone of the spleen and serves as a first line of defense against blood-borne pathogens, as the marginal zone receives large amounts of blood from the general circulation.  They can undergo both T cell-independent and T cell-dependent activation, but preferentially undergo T cell-independent activation. 
- Anemia: low hemoglobin or red blood cells
- Thrombosis: excess blood clotting
- Blood transfusions
- Bone marrow testing
- Antigen-presenting cells ingest an invader and break it into fragments.
- The antigen-presenting cell then combines antigen fragments from the invader with the cell's own HLA molecules.
- The combination of antigen fragments and HLA molecules is moved to the cell’s surface.
- A T cell with a matching receptor on its surface can attach to part of the HLA molecule presenting the antigen fragment, as a key fits into a lock.
- The T cell is then activated and begins fighting the invaders that have that antigen.
- When you get a cut, all sorts of bacteria and viruses enter your body through the break in the skin. When you get a splinter you also have the sliver of wood as a foreign object inside your body. Your immune system responds and eliminates the invaders while the skin heals itself and seals the puncture. In rare cases the immune system misses something and the cut gets infected. It gets inflamed and will often fill with pus. Inflammation and pus are both side-effects of the immune system doing its job.
- When a mosquito bites you, you get a red, itchy bump. That too is a visible sign of your immune system at work.
- Each day you inhale thousands of germs (bacteria and viruses) that are floating in the air. Your immune system deals with all of them without a problem. Occasionally a germ gets past the immune system and you catch a cold, get the flu or worse. A cold or flu is a visible sign that your immune system failed to stop the germ. The fact that you get over the cold or flu is a visible sign that your immune system was able to eliminate the invader after learning about it. If your immune system did nothing, you would never get over a cold or anything else.
- Each day you also eat hundreds of germs, and again most of these die in the saliva or the acid of the stomach. Occasionally, however, one gets through and causes food poisoning. There is normally a very visible effect of this breach of the immune system: vomiting and diarrhea are two of the most common symptoms.
- There are also all kinds of human ailments that are caused by the immune system working in unexpected or incorrect ways that cause problems. For example, some people have allergies. Allergies are really just the immune system overreacting to certain stimuli that other people don't react to at all. Some people have diabetes, which is caused by the immune system inappropriately attacking cells in the pancreas and destroying them. Some people have rheumatoid arthritis, which is caused by the immune system acting inappropriately in the joints. In many different diseases, the cause is actually an immune system error.
- Finally, we sometimes see the immune system because it prevents us from doing things that would be otherwise beneficial. For example, organ transplants are much harder than they should be because the immune system often rejects the transplanted organ.
- Mechanical damage - If you break a bone or tear a ligament you will be "sick" (your body will not be able to perform at its full potential). The cause of the problem is something that is easy to understand and visible.
- Vitamin or mineral deficiency - If you do not get enough vitamin D your body is not able to metabolize calcium properly and you get a disease known as rickets. People with rickets have weak bones (they break easily) and deformities because the bones do not grow properly. If you do not get enough vitamin C you get scurvy, which causes swollen and bleeding gums, swollen joints and bruising. If you do not get enough iron you get anemia, and so on.
- Organ degradation - In some cases an organ is damaged or weakened. For example, one form of "heart disease" is caused by obstructions in the blood vessels leading to the heart muscle, so that the heart does not get enough blood. One form of "liver disease", known as Cirrhosis, is caused by damage to liver cells (drinking too much alcohol is one cause).
- Genetic disease - A genetic disease is caused by a coding error in the DNA. The coding error causes too much or too little of certain proteins to be made, and that causes problems at the cellular level. For example, albinism is caused by a lack of an enzyme called tyrosinase. That missing enzyme means that the body cannot manufacture melanin, the natural pigment that causes hair color, eye color and tanning. Because of the lack of melanin, people with this genetic problem are extremely sensitive to the UV rays in sunlight.
- Cancer - Occasionally a cell will change in a way that causes it to reproduce uncontrollably. For example, when cells in the skin called melanocytes are damaged by ultraviolet radiation in sunlight they change in a characteristic way into a cancerous form of cell. The visible cancer that appears as a tumor on the skin is called melanoma. (See How Sun Tans and Sunburns Work for more information.)
Autoimmune disease can result from abnormal B cell recognition of self-antigens followed by the production of autoantibodies.  Autoimmune diseases where disease activity is correlated with B cell activity include scleroderma, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes, post-infectious IBS, and rheumatoid arthritis. 
A study that investigated the methylome of B cells along their differentiation cycle, using whole-genome bisulfite sequencing (WGBS), showed that there is a hypomethylation from the earliest stages to the most differentiated stages. The largest methylation difference is between the stages of germinal center B cells and memory B cells. Furthermore, this study showed that there is a similarity between B cell tumors and long-lived B cells in their DNA methylation signatures. 
How lupus affects the blood
Blood is made up of many different parts, but those that are most often affected by lupus are the red blood cells, the white blood cells, and the platelets. Blood disorders are common in lupus.
The main issues having to do with lupus and the blood are:
Hematologists, who are specialists in blood disorders, are often involved in the evaluation and treatment of individuals with lupus.
How does lupus affect white blood cells?
White blood cells are actually made up of several different types of cells, including neutrophils (also called granulocytes), lymphocytes and monocytes. White blood cells are the body’s main defense against infection. A reduction in the number of white blood cells is called leukopenia a particular reduction in granulocytes is called neutropenia (or granulocytopenia).
Leukopenia and neutropenia are very common in active lupus, but rarely are white cell counts low enough to lead to infection. Counts may be lowered by azathioprine, cyclophosphamide and some other drugs. Therefore, white cell counts are always monitored during treatment with these agents. If counts go too low, the prescribed drug is usually stopped briefly or the dosage is reduced. When infections occur in lupus, they are more often related to alterations in the body's immune system that are not reflected in routine blood counts.
Plan of Action
A successful immune response to invaders requires
To be able to destroy invaders, the immune system must first recognize them. That is, the immune system must be able to distinguish what is nonself (foreign) from what is self. The immune system can make this distinction because all cells have identification molecules (antigens) on their surface. Microorganisms are recognized because the identification molecules on their surface are foreign.
In people, the most important self-identification molecules are called
HLA molecules are called antigens because if transplanted, as in a kidney or skin graft, they can provoke an immune response in another person (normally, they do not provoke an immune response in the person who has them). Each person has an almost unique combination of HLAs. Each person’s immune system normally recognizes this unique combination as self. A cell with molecules on its surface that are not identical to those on the body’s own cells is identified as being foreign. The immune system then attacks that cell. Such a cell may be a cell from transplanted tissue or one of the body’s cells that has been infected by an invading microorganism or altered by cancer. (HLA molecules are what doctors try to match when a person needs an organ transplant.)
Some white blood cells—B cells (B lymphocytes)—can recognize invaders directly. But others—T cells (T lymphocytes)—need help from cells called antigen-presenting cells:
How T Cells Recognize Antigens
T cells are part of the immune surveillance system. They travel through the bloodstream and lymphatic system. When they reach the lymph nodes or another secondary lymphoid organ, they look for foreign substances (antigens) in the body. However, before they can fully recognize and respond to a foreign antigen, the antigen must be processed and presented to the T cell by another white blood cell, called an antigen-presenting cell. Antigen-presenting cells consist of dendritic cells (which are the most effective), macrophages, and B cells.
Activation and mobilization
White blood cells are activated when they recognize invaders. For example, when the antigen-presenting cell presents antigen fragments bound to HLA to a T cell, the T cell attaches to the fragments and is activated. B cells can be activated directly by invaders. Once activated, white blood cells ingest or kill the invader or do both. Usually, more than one type of white blood cell is needed to kill an invader.
Immune cells, such as macrophages and activated T cells, release substances that attract other immune cells to the trouble spot, thus mobilizing defenses. The invader itself may release substances that attract immune cells.
The immune response must be regulated to prevent extensive damage to the body, as occurs in autoimmune disorders. Regulatory (suppressor) T cells help control the response by secreting cytokines (chemical messengers of the immune system) that inhibit immune responses. These cells prevent the immune response from continuing indefinitely.
Resolution involves confining the invader and eliminating it from the body. After the invader is eliminated, most white blood cells self-destruct and are ingested. Those that are spared are called memory cells. The body retains memory cells, which are part of acquired immunity, to remember specific invaders and respond more vigorously to them at the next encounter.
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How the Immune System Fights Disease
The immune system is a complex network of cells and chemicals. Its mission is to protect us against foreign organisms and substances. The cells in the immune system have the ability to recognize something as either "self" or "invader," and they try to get rid of anything that is an invader. Many different kinds of cells, and hundreds of different chemicals, must be coordinated for the immune system to function smoothly.
The immune system can mount a variety of responses to attack specific invader organisms. One of these responses is coordinated by T-helper cells (also known as T cells, T4 cells, or CD4 cells), which act as a kind of orchestra conductor. The T-helper cells tell other cells what to do when this response is triggered. We are interested in this immune response because it is the one that is most disrupted by HIV infection. As HIV succeeds in destroying more and more of these important cells, the ability to fight off other infections gradually declines. If the "coordinator" of the process, the T-helper cell, is no longer functioning, other cells in the immune system cannot perform their functions, leaving the body open to attack by opportunistic infections.
Normal T Cell Response to Infection
Let's look first at how the immune response coordinated by the T cells is supposed to work. Please keep in mind that we will be explaining only one of the body's immune responses.
Any infectious agent (Figure 1) that enters your body will eventually be taken up in your lymphatic system.
This may happen very soon after infection, or it may not happen until the invader has found a niche and begun to replicate. In one of your lymph nodes, the infectious agent (which we will call "Virus" in the figures) will bump into a macrophage (literally "big eater"). The macrophage will ingest the invader (Figure 2).
Then the macrophage takes the invader apart and displays the viral antigens on its surface for other immune cells to read (Figure 3).
Antigens are proteins specific to each particular microorganism. The antigens act as an identity card that allows our immune system to recognize invader organisms that need to be eliminated.
After displaying the agent's antigens, the macrophage will send out a message to a T-helper cell to read and recognize the antigens (Figure 4).
This message activates T-helper cells and triggers the immune response. Once the T cell has read the antigens, it will send out messages to activate other cells, known as B cells (Figure 5), which will in turn come and read the antigens from the macrophage's surface (Figure 6).
The activated B cell will then produce millions of antibodies (Figure 7). The antibody is a protein that will bind to an antigen. Each antibody is unique and specific for example, a measles antibody will only bind to a measles virus. We produce antibodies because, given the high concentration of infectious agent that is needed to cause disease, our macrophages could not go after the invaders alone. However, antibodies can outnumber the invaders and help us get rid of them.
How do the antibodies bind to the infectious agent? The antibody resembles the mirror image of the antigen (like a key and a lock), usually providing such a close fit that, if they bump into each other, the antibody will grab the antigen and hang on (Figure 8). Once an antibody has "caught" an invader, it will broadcast a signal that says "eat me and whatever I have captured" (Figure 9). A macrophage will in turn get the message and will devour the antibody-antigen complex and rid the body of the infectious agent (Figure 10).
Eventually, as this process continues, the number of infectious agents will decrease and the body will need to stop the battle. However, all the cells are still activated and the immune system needs to put them to rest. Another kind of T cell, the T-suppressor cell (or T8 cell), will send out messages to the other cells and "de-activate" them (Figure 11). Without the T-suppressor cells, the body would continue trying to fight off a disease that no longer exists (and eventually would end up fighting its own cells).
HIV Interferes With Normal Immune Response
With HIV infection, this procedure does not work adequately. Initially, macrophages recognize the HIV, T-helper cells initiate the response, and B cells produce antibodies. However, although effective at first, the antibodies do not eliminate the infection. Although some HIV might get killed, many more viruses will actively infect T-helper cells -- the very same cells that are supposed to coordinate the defense against the virus. Infected T cells become virus factories which, if activated, will produce more copies of the virus instead of triggering the production of more antibodies against HIV.
How Your Immune System Works
Inside your body there is an amazing protection mechanism called the immune system. It is designed to defend you against millions of bacteria, microbes, viruses, toxins and parasites that would love to invade your body. To understand the power of the immune system, all that you have to do is look at what happens to anything once it dies. That sounds gross, but it does show you something very important about your immune system.
When something dies, its immune system (along with everything else) shuts down. In a matter of hours, the body is invaded by all sorts of bacteria, microbes, parasites. None of these things are able to get in when your immune system is working, but the moment your immune system stops the door is wide open. Once you die it only takes a few weeks for these organisms to completely dismantle your body and carry it away, until all that's left is a skeleton. Obviously your immune system is doing something amazing to keep all of that dismantling from happening when you are alive.
The immune system is complex, intricate and interesting. And there are at least two good reasons for you to know more about it. First, it is just plain fascinating to understand where things like fevers, hives, inflammation, etc., come from when they happen inside your own body. You also hear a lot about the immune system in the news as new parts of it are understood and new drugs come on the market -- knowing about the immune system makes these news stories understandable. In this article, we will take a look at how your immune system works so that you can understand what it is doing for you each day, as well as what it is not.
Seeing Your Immune System
Your immune system works around the clock in thousands of different ways, but it does its work largely unnoticed. One thing that causes us to really notice our immune system is when it fails for some reason. We also notice it when it does something that has a side effect we can see or feel. Here are several examples:
Basics of the Immune System
Let's start at the beginning. What does it mean when someone says "I feel sick today?" What is a disease? By understanding the different kinds of diseases it is possible to see what types of disease the immune system helps you handle.
When you "get sick", your body is not able to work properly or at its full potential. There are many different ways for you to get sick -- here are some of them:
Viral or Bacterial Infection
When a virus or bacteria (also known generically as a germ) invades your body and reproduces, it normally causes problems. Generally the germ's presence produces some side effect that makes you sick. For example, the strep throat bacteria (Streptococcus) releases a toxin that causes inflammation in your throat. The polio virus releases toxins that destroy nerve cells (often leading to paralysis). Some bacteria are benign or beneficial (for example, we all have millions of bacteria in our intestines and they help digest food), but many are harmful once they get into the body or the bloodstream.
Viral and bacterial infections are by far the most common causes of illness for most people. They cause things like colds, influenza, measles, mumps, malaria, AIDS and so on.
The job of your immune system is to protect your body from these infections. The immune system protects you in three different ways:
- It creates a barrier that prevents bacteria and viruses from entering your body.
- If a bacteria or virus does get into the body, the immune system tries to detect and eliminate it before it can make itself at home and reproduce.
- If the virus or bacteria is able to reproduce and start causing problems, your immune system is in charge of eliminating it.
The immune system also has several other important jobs. For example, your immune system can detect cancer in early stages and eliminate it in many cases.
Your body is a multi-cellular organism made up of perhaps 100 trillion cells. The cells in your body are fairly complicated machines. Each one has a nucleus, energy production equipment, etc. Bacteria are single-celled organisms that are much simpler. For example, they have no nucleus. They are perhaps 1/100th the size of a human cell and might measure 1 micrometer long. Bacteria are completely independent organisms able to eat and reproduce - they are sort of like fish swimming in the ocean of your body. Under the right conditions bacteria reproduce very quickly: One bacteria divides into two separate bacteria perhaps once every 20 or 30 minutes. At that rate, one bacteria can become millions in just a few hours.
A virus is a different breed altogether. A virus is not really alive. A virus particle is nothing but a fragment of DNA in a protective coat. The virus comes in contact with a cell, attaches itself to the cell wall and injects its DNA (and perhaps a few enzymes) into the cell. The DNA uses the machinery inside the living cell to reproduce new virus particles. Eventually the hijacked cell dies and bursts, freeing the new virus particles or the viral particles may bud off of the cell so it remains alive. In either case, the cell is a factory for the virus.
Components of the Immune System
One of the funny things about the immune system is that it has been working inside your body your entire life but you probably know almost nothing about it. For example, you are probably aware that inside your chest you have an organ called a "heart". Who doesn't know that they have a heart? You have probably also heard about the fact that you have lungs and a liver and kidneys. But have you even heard about your thymus? There's a good chance you don't even know that you have a thymus, yet its there in your chest right next to your heart. There are many other parts of the immune system that are just as obscure, so let's start by learning about all of the parts.
The most obvious part of the immune system is what you can see. For example, skin is an important part of the immune system. It acts as a primary boundary between germs and your body. Part of your skin's job is to act as a barrier in much the same way we use plastic wrap to protect food. Skin is tough and generally impermeable to bacteria and viruses. The epidermis contains special cells called Langerhans cells (mixed in with the melanocytes in the basal layer) that are an important early-warning component in the immune system. The skin also secretes antibacterial substances. These substances explain why you don't wake up in the morning with a layer of mold growing on your skin -- most bacteria and spores that land on the skin die quickly.
Your nose, mouth and eyes are also obvious entry points for germs. Tears and mucus contain an enzyme (lysozyme) that breaks down the cell wall of many bacteria. Saliva is also anti-bacterial. Since the nasal passage and lungs are coated in mucus, many germs not killed immediately are trapped in the mucus and soon swallowed. Mast cells also line the nasal passages, throat, lungs and skin. Any bacteria or virus that wants to gain entry to your body must first make it past these defenses.
Once inside the body, a germ deals with the immune system at a different level. The major components of the immune system are:
- Lymph system
- Bone marrow
- White blood cells
- Complement system
Let's look at each of these components in detail.
The lymph system is most familiar to people because doctors and mothers often check for "swollen lymph nodes" in the neck. It turns out that the lymph nodes are just one part of a system that extends throughout your body in much the same way your blood vessels do. The main difference between the blood flowing in the circulatory system and the lymph flowing in the lymph system is that blood is pressurized by the heart, while the lymph system is passive. There is no "lymph pump" like there is a "blood pump" (the heart). Instead, fluids ooze into the lymph system and get pushed by normal body and muscle motion to the lymph nodes. This is very much like the water and sewer systems in a community. Water is actively pressurized, while sewage is passive and flows by gravity.
Lymph is a clearish liquid that bathes the cells with water and nutrients. Lymph is blood plasma -- the liquid that makes up blood minus the red and white cells. Think about it -- each cell does not have its own private blood vessel feeding it, yet it has to get food, water, and oxygen to survive. Blood transfers these materials to the lymph through the capillary walls, and lymph carries it to the cells. The cells also produce proteins and waste products and the lymph absorbs these products and carries them away. Any random bacteria that enter the body also find their way into this inter-cell fluid. One job of the lymph system is to drain and filter these fluids to detect and remove the bacteria. Small lymph vessels collect the liquid and move it toward larger vessels so that the fluid finally arrives at the lymph nodes for processing.
Lymph nodes contain filtering tissue and a large number of lymph cells. When fighting certain bacterial infections, the lymph nodes swell with bacteria and the cells fighting the bacteria, to the point where you can actually feel them. Swollen lymph nodes are therefore a good indication that you have an infection of some sort.
Once lymph has been filtered through the lymph nodes it re-enters the bloodstream.
The thymus lives in your chest, between your breast bone and your heart. It is responsible for producing T-cells (see the next section), and is especially important in newborn babies - without a thymus a baby's immune system collapses and the baby will die. The thymus seems to be much less important in adults - for example, you can remove it and an adult will live because other parts of the immune system can handle the load. However, the thymus is important, especially to T cell maturation (as we will see in the section on white blood cells below).
The spleen filters the blood looking for foreign cells (the spleen is also looking for old red blood cells in need of replacement). A person missing their spleen gets sick much more often than someone with a spleen.
Bone marrow produces new blood cells, both red and white. In the case of red blood cells the cells are fully formed in the marrow and then enter the bloodstream. In the case of some white blood cells, the cells mature elsewhere. The marrow produces all blood cells from stem cells. They are called "stem cells" because they can branch off and become many different types of cells - they are precursors to different cell types. Stem cells change into actual, specific types of white blood cells.
White blood cells
White blood cells are described in detail in the next section.
Antibodies (also referred to as immunoglobulins and gammaglobulins) are produced by white blood cells. They are Y-shaped proteins that each respond to a specific antigen (bacteria, virus or toxin). Each antibody has a special section (at the tips of the two branches of the Y) that is sensitive to a specific antigen and binds to it in some way. When an antibody binds to a toxin it is called an antitoxin (if the toxin comes from some form of venom, it is called an antivenin). The binding generally disables the chemical action of the toxin. When an antibody binds to the outer coat of a virus particle or the cell wall of a bacterium it can stop their movement through cell walls. Or a large number of antibodies can bind to an invader and signal to the complement system that the invader needs to be removed.
Antibodies come in five classes:
- Immunoglobulin A (IgA)
- Immunoglobulin D (IgD)
- Immunoglobulin E (IgE)
- Immunoglobulin G (IgG)
- Immunoglobulin M (IgM)
Whenever you see an abbreviation like IgE in a medical document, you now know that what they are talking about is an antibody.
For additional information on antibodies see The Antibody Resource Page.
The complement system, like antibodies, is a series of proteins. There are millions of different antibodies in your blood stream, each sensitive to a specific antigen. There are only a handful of proteins in the complement system, and they are floating freely in your blood. Complements are manufactured in the liver. The complement proteins are activated by and work with (complement) the antibodies, hence the name. They cause lysing (bursting) of cells and signal to phagocytes that a cell needs to be removed.
For additional information on complements, see The Complement System.
There are several hormones generated by components of the immune system. These hormones are known generally as lymphokines. It is also known that certain hormones in the body suppress the immune system. Steroids and corticosteroids (components of adrenaline) suppress the immune system.
Tymosin (thought to be produced by the thymus) is a hormone that encourages lymphocyte production (a lymphocyte is a form of white blood cell - see below). Interleukins are another type of hormone generated by white blood cells. For example, Interleukin-1 is produced by macrophages after they eat a foreign cell. IL-1 has an interesting side-effect - when it reaches the hypothalamus it produces fever and fatigue. The raised temperature of a fever is known to kill some bacteria.
Tumor Necrosis Factor
Tumor Necrosis Factor (TNF) is also produced by macrophages. It is able to kill tumor cells, and it also promotes the creation of new blood vessels so it is important to healing.
Interferon interferes with viruses (hence the name) and is produced by most cells in the body. Interferons, like antibodies and complements, are proteins, and their job is to let cells signal to one another. When a cell detects interferon from other cells, it produces proteins that help prevent viral replication in the cell.
You are probably aware of the fact that you have "red blood cells" and "white blood cells" in your blood. The white blood cells are probably the most important part of your immune system. And it turns out that "white blood cells" are actually a whole collection of different cells that work together to destroy bacteria and viruses. Here are all of the different types, names and classifications of white blood cells working inside your body right now:
- Plasma cells
- Helper T-cells
- Killer T-cells
- Suppressor T-cells
- Natural killer cells
Learning all of these different names and the function of each cell type takes a bit of effort, but you can understand scientific articles a lot better once you get it all figured out! Here's a quick summary to help you get all of the different cell types organized in your brain.
All white blood cells are known officially as leukocytes. White blood cells are not like normal cells in the body -- they actually act like independent, living single-cell organisms able to move and capture things on their own. White blood cells behave very much like amoeba in their movements and are able to engulf other cells and bacteria. Many white blood cells cannot divide and reproduce on their own, but instead have a factory somewhere in the body that produces them. That factory is the bone marrow.
Leukocytes are divided into three classes:
- Granulocytes - Granulocytes make up 50% to 60% of all leukocytes. Granulocytes are themselves divided into three classes: neutrophils, eosinophils and basophils. Granulocytes get their name because they contain granules, and these granules contain different chemicals depending on the type of cell.
- Lymphocyte - Lymphocytes make up 30% to 40% of all leukocytes. Lymphocytes come in two classes: B cells (those that mature in bone marrow) and T cells (those that mature in the thymus).
- Monocyte - Monocytes make up 7% or so of all leukocytes. Monocytes evolve into macrophages.
All white blood cells start in bone marrow as stem cells. Stem cells are generic cells that can form into the many different types of leukocytes as they mature. For example, you can take a mouse, irradiate it to kill off its bone marrow's ability to produce new blood cells, and then inject stem cells into the mouse's blood stream. The stem cells will divide and differentiate into all different types of white blood cells. A "bone marrow transplant" is accomplished simply by injecting stem cells from a donor into the blood stream. The stem cells find their way, almost magically, into the marrow and make their home there.
Each of the different types of white blood cells have a special role in the immune system, and many are able to transform themselves in different ways. The following descriptions help to understand the roles of the different cells.
- Neutrophils are by far the most common form of white blood cells that you have in your body. Your bone marrow produces trillions of them every day and releases them into the bloodstream, but their life span is short -- generally less than a day. Once in the bloodstream neutrophils can move through capillary walls into tissue. Neutorphils are attracted to foreign material, inflammation and bacteria. If you get a splinter or a cut, neutrophils will be attracted by a process called chemotaxis. Many single-celled organisms use this same process -- chemotaxis lets motile cells move toward higher concentrations of a chemical. Once a neutrophil finds a foreign particle or a bacteria it will engulf it, releasing enzymes, hydrogen peroxide and other chemicals from its granules to kill the bacteria. In a site of serious infection (where lots of bacteria have reproduced in the area), pus will form. Pus is simply dead neutrophils and other cellular debris.
- Eosinophils and basophils are far less common than neutrophils. Eosinophils seem focused on parasites in the skin and the lungs, while Basophils carry histamine and therefore important (along with mast cells) to causing inflammation. From the immune system's standpoint inflammation is a good thing. It brings in more blood and it dilates capillary walls so that more immune system cells can get to the site of infection.
- Of all blood cells, macrophages are the biggest (hence the name "macro"). Monocytes are released by the bone marrow, float in the bloodstream, enter tissue and turn into macrophages. Most boundary tissue has its own devoted macrophages. For example, alveolar macrophages live in the lungs and keep the lungs clean (by ingesting foreign particles like smoke and dust) and disease free (by ingesting bacteria and microbes). Macrophages are called langerhans cells when they live in the skin. Macrophages also swim freely. One of their jobs is to clean up dead neutrophils -- macropghages clean up pus, for example, as part of the healing process.
- The lymphocytes handle most of the bacterial and viral infections that we get. Lymphocytes start in the bone marrow. Those destined to become B cells develop in the marrow before entering the bloodstream. T cells start in the marrow but migrate through the bloodstream to the thymus and mature there. T cells and B cells are often found in the bloodstream but tend to concentrate in lymph tissue such as the lymph nodes, the thymus and the spleen. There is also quite a bit of lymph tissue in the digestive system. B cells and T cells have different functions.
- B cells, when stimulated, mature into plasma cells -- these are the cells that produce antibodies. A specific B cell is tuned to a specific germ, and when the germ is present in the body the B cell clones itself and produces millions of antibodies designed to eliminate the germ.
- T cells, on the other hand, actually bump up against cells and kill them. T cells known as Killer T cells can detect cells in your body that are harboring viruses, and when it detects such a cell it kills it. Two other types of T cells, known as Helper and Suppressor T cells, help sensitize killer T cells and control the immune response.
Helper T cells are actually quite important and interesting. They are activated by Interleukin-1, produced by macrophages. Once activated, Helper T cells produce Interleukin-2, then interferon and other chemicals. These chemicals activate B cells so that they produce antibodies. The complexity and level of interaction between neutrophils, macrophages, T cells and B cells is really quite amazing.
Because white blood cells are so important to the immune system, they are used as a measure of immune system health. When you hear that someone has a "strong immune system" or a "suppressed immune system", one way it was determined was by counting different types of white blood cells in a blood sample. A normal white blood cell count is in the range of 4,000 to 11,000 cells per microliter of blood. 1.8 to 2.0 helper T-cells per suppressor T-cell is normal. A normal absolute neutrophil count (ANC) is in the range of 1,500 to 8,000 cells per microliter. An article like Introduction to Hematology can help you learn more about white blood cells in general and the different types of white blood cells found in your body.
One important question to ask about white blood cells (and several other parts of the immune system) is, "How does a white blood cell know what to attack and what to leave alone? Why doesn't a white blood cell attack every cell in the body?" There is a system built into all of the cells in your body called the Major Histocompatibility Complex (MHC) (also known as the Human Leukocyte Antigen (HLA)) that marks the cells in your body as "you". Anything that the immune system finds that does not have these markings (or that has the wrong markings) is definitely "not you" and is therefore fair game. Encyclopedia Britannica has this to say about the MHC:
"There are two major types of MHC protein molecules--class I and class II--that span the membrane of almost every cell in an organism. In humans these molecules are encoded by several genes all clustered in the same region on chromosome 6. Each gene has an unusual number of alleles (alternate forms of a gene). As a result, it is very rare for two individuals to have the same set of MHC molecules, which are collectively called a tissue type.
MHC molecules are important components of the immune response. They allow cells that have been invaded by an infectious organism to be detected by cells of the immune system called T lymphocytes, or T cells. The MHC molecules do this by presenting fragments of proteins (peptides) belonging to the invader on the surface of the cell. The T cell recognizes the foreign peptide attached to the MHC molecule and binds to it, an action that stimulates the T cell to either destroy or cure the infected cell. In uninfected healthy cells the MHC molecule presents peptides from its own cell (self peptides), to which T cells do not normally react. However, if the immune mechanism malfunctions and T cells react against self peptides, an autoimmune disease arises."
There are many diseases that, if you catch them once, you will never catch again. Measles is a good example, as is chicken pox. What happens with these diseases is that they make it into your body and start reproducing. The immune system gears up to eliminate them. In your body you already have B cells that can recognize the virus and produce antibodies for it. However, there are only a few of these cells for each antibody. Once a particlular disease is recognized by these few specific B cells, the B cells turn into plasma cells, clone themselves and start pumping out antibodies. This process takes time, but the disease runs it course and is eventually eliminated. However, while it is being eliminated, other B cells for the disease clone themselves but do not generate antibodies. This second set of B cells remains in your body for years, so if the disease reappears your body is able to eliminate it immediately before it can do anything to you.
A vaccine is a weakened form of a disease. It is either a killed form of the disease, or it is a similar but less virulent strain. Once inside your body your immune system mounts the same defense, but because the disease is different or weaker you get few or no symptoms of the disease. Now, when the real disease invades your body, your body is able to eliminate it immediately.
Vaccines exist for all sorts of diseases, both viral and bacterial: measles, mumps, whooping cough, tuberculosis, smallpox, polio, typhoid, etc.
Many diseases cannot be cured by vaccines, however. The common cold and Influenza are two good examples. These diseases either mutate so quickly or have so many different strains in the wild that it is impossible to inject all of them into your body. Each time you get the flu, for example, you are getting a different strain of the same disease.
AIDS (Acquired Immune Deficiency Syndrome) is a disease caused by HIV (the Human Immunodeficiency Virus). This is a particularly problematic disease for the immune system because the virus actually attacks immune system cells. In particular, it reproduces inside Helper T cells and kills them in the process. Without Helper T cells to orchestrate things, the immune system eventually collapses and the victim dies of some other infection that the immune system would normally be able to handle. See How AIDS Works as well as the links below for more information.
Sometimes your immune system is not able to activate itself quickly enough to outpace the reproductive rate of a certain bacteria, or the bacteria is producing a toxin so quickly that it will cause permanent damage before the immune system can eliminate the bacteria. In these cases it would be nice to help the immune system by killing the offending bacteria directly.
Antibiotics work on bacterial infections. Antibiotics are chemicals that kill the bacteria cells but do not affect the cells that make up your body. For example, many antibiotics interrupt the machinery inside bacterial cells that builds the cell wall. Human cells do not contain this machinery, so they are unaffected. Different antibiotics work on different parts of bacterial machinery, so each one is more or less effective on specific types of bacteria. You can see that, because a virus is not alive, antibiotics have no effect on a virus.
One problem with antibiotics is that they lose effectiveness over time. If you take an antibiotic it will normally kill all of the bacteria it targets over the course of a week or 10 days. You will feel better very quickly (in just a day or two) because the antibiotic kills the majority of the targeted bacteria very quickly. However, on occasion one of the bacterial offspring will contain a mutation that is able to survive the specific antibiotic. This bacteria will then reproduce and the whole disease mutates. Eventually the new strain is infecting everyone and the old antibiotic has no effect on it. This process has become more and more of a problem over time and has become a significant concern in the medical community.
Sometimes the immune system makes a mistake. One type of mistake is called autoimmunity: the immune system for some reason attacks your own body in the same way it would normally attack a germ. Two common diseases are caused by immune system mistakes. Juvenile-onset diabetes is caused by the immune system attacking and eliminating the cells in the pancreas that produce insulin. Rheumatoid arthritis is caused by the immune system attacking tissues inside the joints.
Allergies are another form of immune system error. For some reason, in people with allergies, the immune system strongly reacts to an allergen that should be ignored. The allergen might be a certain food, or a certain type of pollen, or a certain type of animal fur. For example, a person allergic to a certain pollen will get a runny nose, watery eyes, sneezing, etc. This reaction is caused primarily by mast cells in the nasal passages. In reaction to the pollen the mast cells release histamine. Histamine has the effect of causing inflammation, which allows fluid to flow from blood vessels. Histamine also causes itching. To eliminate these symptoms the drug of choice is, of course, an antihistamine.
The last example of an immune system mistake is the effect the immune system has on transplanted tissue. This really isn't a mistake, but it makes organ and tissue transplants nearly impossible. When the foreign tissue is placed inside your body, its cells do not contain the correct identification. Your immune system therefore attacks the tissue. The problem cannot be prevented, but can be diminished by carefully matching the tissue donor with the recipient and by using immunosuppressing drugs to try to prevent an immune system reaction. Of course, by suppressing the immune system these drugs open the patient to opportunistic infections.
For more information on the immune system and related topics, check out the links on the next page.
The immune system protects the body from possibly harmful substances by recognizing and responding to antigens. Antigens are substances (usually proteins) on the surface of cells, viruses, fungi, or bacteria. Nonliving substances such as toxins, chemicals, drugs, and foreign particles (such as a splinter) can also be antigens. The immune system recognizes and destroys, or tries to destroy, substances that contain antigens.
Your body's cells have proteins that are antigens. These include a group of antigens called HLA antigens. Your immune system learns to see these antigens as normal and usually does not react against them.
Innate, or nonspecific, immunity is the defense system with which you were born. It protects you against all antigens. Innate immunity involves barriers that keep harmful materials from entering your body. These barriers form the first line of defense in the immune response. Examples of innate immunity include:
- Enzymes in tears and skin oils
- Mucus, which traps bacteria and small particles
- Stomach acid
Innate immunity also comes in a protein chemical form, called innate humoral immunity. Examples include the body's complement system and substances called interferon and interleukin-1 (which causes fever).
If an antigen gets past these barriers, it is attacked and destroyed by other parts of the immune system.
Acquired immunity is immunity that develops with exposure to various antigens. Your immune system builds a defense against that specific antigen.
Passive immunity is due to antibodies that are produced in a body other than your own. Infants have passive immunity because they are born with antibodies that are transferred through the placenta from their mother. These antibodies disappear between ages 6 and 12 months.
Passive immunization may also be due to injection of antiserum, which contains antibodies that are formed by another person or animal. It provides immediate protection against an antigen, but does not provide long-lasting protection. Immune serum globulin (given for hepatitis exposure) and tetanus antitoxin are examples of passive immunization.
The immune system includes certain types of white blood cells. It also includes chemicals and proteins in the blood, such as antibodies, complement proteins, and interferon. Some of these directly attack foreign substances in the body, and others work together to help the immune system cells.
Lymphocytes are a type of white blood cell. There are B and T type lymphocytes.
- B lymphocytes become cells that produce antibodies. Antibodies attach to a specific antigen and make it easier for the immune cells to destroy the antigen.
- T lymphocytes attack antigens directly and help control the immune response. They also release chemicals, known as cytokines, which control the entire immune response.
As lymphocytes develop, they normally learn to tell the difference between your own body tissues and substances that are not normally found in your body. Once B cells and T cells are formed, a few of those cells will multiply and provide "memory" for your immune system. This allows your immune system to respond faster and more efficiently the next time you are exposed to the same antigen. In many cases, it will prevent you from getting sick. For example, a person who has had chickenpox or has been immunized against chickenpox is immune from getting chickenpox again.
The inflammatory response (inflammation) occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause. The damaged cells release chemicals including histamine, bradykinin, and prostaglandins. These chemicals cause blood vessels to leak fluid into the tissues, causing swelling. This helps isolate the foreign substance from further contact with body tissues.
The chemicals also attract white blood cells called phagocytes that "eat" germs and dead or damaged cells. This process is called phagocytosis. Phagocytes eventually die. Pus is formed from a collection of dead tissue, dead bacteria, and live and dead phagocytes.
IMMUNE SYSTEM DISORDERS AND ALLERGIES
Immune system disorders occur when the immune response is directed against body tissue, is excessive, or is lacking. Allergies involve an immune response to a substance that most people's bodies perceive as harmless.
Vaccination (immunization) is a way to trigger the immune response. Small doses of an antigen, such as dead or weakened live viruses, are given to activate immune system "memory" (activated B cells and sensitized T cells). Memory allows your body to react quickly and efficiently to future exposures.
COMPLICATIONS DUE TO AN ALTERED IMMUNE RESPONSE
An efficient immune response protects against many diseases and disorders. An inefficient immune response allows diseases to develop. Too much, too little, or the wrong immune response causes immune system disorders. An overactive immune response can lead to the development of autoimmune diseases, in which antibodies form against the body's own tissues.
Complications from altered immune responses include:
- Allergy or hypersensitivity , a life-threatening allergic reaction
- Autoimmune disorders , a complication of a bone marrow transplant
- Immunodeficiency disorders
- Transplant rejection
What is the immune system?
We are surrounded by millions of bacteria, viruses and other germs (microbes) that have the potential to enter our bodies and cause harm. The immune system is the body's defence against disease-causing microbes (pathogens).
The immune system is made up of non-specialised defences such as your skin (acting as a barrier) and strong acid stomach juices. However it also has some highly specialised defences which give you resistance to particular pathogens. Another name for this resistance is immunity. These defences are special white blood cells called lymphocytes. Other types of white blood cells play an important part in defending your body against infection.
The lymphatic system is also part of the immune system. The lymphatic system is made up of a network of tubes (vessels) which carry fluid called lymph. It contains specialised lymph tissue and all of the structures dedicated to the production of lymphocytes.
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Immunological memory refers to the ability of B and T cells to produce long-lived memory cells that defend against specific pathogens.
Describe immunological memory of the immune system
- When B and T cells begin to replicate, some offspring will become long-lived memory cells.
- Memory cells remember all specific pathogens encountered during the animal’s lifetime and can thus call forth a strong response if the pathogen ever invades the body again.
- Passive immunity comes from IgG antibodies given through the mother during fetal development and through breast milk. This memory is short term, but protects the infant until its own adaptive immune system is functional.
- During a secondary immune response, memory B and T cells work to rapidly eliminate the pathogen, preventing reinfection by the same pathogen.
- During a vaccination, the antigen of a pathogen is introduced into the body through a weakened form of the pathogen that cannot cause an infection. This stimulates the immune system to develop a specific immunity against that pathogen without actually causing the disease that the pathogen brings.
- Vaccines do not exist for every pathogen due to frequent strain mutations and challenges in producing an immunization strong enough to work, but not strong enough to cause an infection.
- secondary immune response: The act of exposure to the same pathogen after the initial immune response. Memory B and T cells work to rapidly eliminate the pathogen to prevent reinfection.
- vaccination: Inoculation with the weakened form of a pathogen to protect against a particular disease or strain of disease by stimulating the development of immunological memory against that pathogen.
When B and T cells begin to replicate during an adaptive immune response, some offspring become long-lived memory cells. These memory cells remember all specific pathogens encountered during the animal’s lifetime and can thus call forth a stronger response, called the secondary immune response, if the pathogen ever invades the body again. The adaptive immune system is so-named because it is a result of an adaptation to an infection. Immunological memory can either exist in active long-term memory or passive short-term memory.
Immune response: When B and T cells begin to replicate, some of the offspring that they produce will end up becoming long-lived memory cells. These memory cells will remember all specific pathogens encountered during the animal’s lifetime and can thus call forth a strong response if the pathogen ever invades the body again.
Newborn infants are particularly vulnerable to infections since they have no prior exposure to pathogens. Thus, the mother protects the infant through several layers of passive protection. During pregnancy, IgG, a certain isotype of antibody, is transported to the baby from the mother through the placenta, so even babies have high levels of antibodies with similar antigen specificities as the mother. Even breast milk contains antibodies that are transferred to the infant’s gastrointestinal tract and protect against bacterial infections until the baby is capable of making its own antibodies. Since the fetus isn’t making any memory cells or antibodies, this is called passive immunity. Passive immunity is short-lived, ranging from a couple days to a couple months.
As the infant matures, their thymus and bone marrow work to raise a stock of mature lymphocytes that form the foundation for the infant’s personal adaptive immune system. Because the passive memory comes from antibodies instead of B cells themselves, infants do not inherit long-term immunological memory from the mother. Even if the infant receives antibodies specific to certain diseases from its mother, the infant wouldn’t be able to bolster a long-term memory that would direct antigen exposure and presentation.
Active Memory and Immunization
Following an infection, long-term active memory is acquired by activation of B and T cells. Memory cells derive from their parent B and T cells, and undergo clonal selection following infection, which increases antigen-binding affinity. Following reinfection, the secondary immune response typically eliminates the pathogen before symptoms of an infection can occur. During the secondary immune response, memory T cells rapidly proliferate into active helper and cytotoxic T cells specific to that antigen, while memory B cells rapidly produce antibodies to neutralize the pathogen. Long-term active memory consists of rapid response and form permanent immunological memory so long as those memory cells survive.
Vaccinations take advantage of memory lymphocyte development by artificially-generating active immunity, a process called immunization. During a vaccination, the antigen of a pathogen is introduced into the body and stimulates the immune system to develop a specific immunity against that pathogen. It doesn’t cause the disease that the pathogen brings because the vaccine uses an attenuated form of the pathogen that contains the same antigen but doesn’t have the capacity for replication. This deliberate introduction of the pathogen is successful since it exploits the immune system’s natural specificity and inducibility. Vaccination is an extremely effective manipulation of the immune system that helps fight diseases. Over the course of vaccine development, they have saved countless lives, and diseases like rubella and polio are not the widespread causes of disability they once were.
Despite the effectiveness of vaccines, methods do not yet exist to develop vaccines for every pathogen. Many pathogens undergo mutations that change the expression of their antigens, making immunization attempts fruitless for diseases like the common cold or norovirus. Many parasitic pathogens, such as the plasmodium protist that causes malaria, haven’t successfully been vaccinated against because it is challenging to develop a vaccine that is strong enough to stimulate an immune response (sufficient immunogenicity) without causing a live infection.