- Immune system questions
- Innate immunity
- Adaptive immunity
- Role of phagocytes in innate or nonspecific immunity
- Types of immune responses: Innate and adaptive, humoral vs. cell-mediated
- B lymphocytes (B cells)
- Professional antigen presenting cells (APC) and MHC II complexes
- Helper T cells
- Cytotoxic T cells
- Review of B cells, CD4+ T cells and CD8+ T cells
- Clonal selection
- Self vs. non-self immunity
- How white blood cells move around
- Blood cell lineages
Have you ever wondered how your recovery time for the common cold, the flu, or small infections seems to get shorter after you’ve been exposed and successfully recovered the first time? The adaptive immune system, also called acquired immunity, uses specific antigens to strategically mount an immune response. Unlike the innate immune system, which attacks only based on the identification of general threats, the adaptive immunity is activated by exposure to pathogens, and uses an immunological memory to learn about the threat and enhance the immune response accordingly. The adaptive immune response is much slower to respond to threats and infections than the innate immune response, which is primed and ready to fight at all times.
Cells of the adaptive immune system
Unlike the innate immune system, the adaptive immune system relies on fewer types of cells to carry out its tasks: B cells and T cells.
Both B cells and T cells are lymphocytes that are derived from specific types of stem cells, called multipotent hematopoietic stem cells, in the bone marrow. After they are made in the bone marrow, they need to mature and become activated. Each type of cell follows different paths to their final, mature forms.
After formation and maturation in the bone marrow (hence the name “B cell”), the naive B cells move into the lymphatic system to circulate throughout the body. In the lymphatic system, naive B cells encounter an antigen, which starts the maturation process for the B cell. B cells each have one of millions of distinctive surface antigen-specific receptors that are inherent to the organism’s DNA. For example, naive B cells express antibodies on their cell surface, which can also be called membrane-bound antibodies.
B cell and membrane-bound antibodies
When a naive B cell encounters an antigen that fits or matches its membrane-bound antibody, it quickly divides in order to become either a memory B cell or an effector B cell, which is also called a plasma cell. Antibodies can bind to antigens directly.
Antigen binding to B cell antigen binding site
The antigen must effectively bind with a naive B cell’s membrane-bound antibody in order to set off differentiation, or the process of becoming one of the new forms of a B cell.
B cell differentiation process resulting in plasma cell and memory B cell
Memory B cells express the same membrane-bound antibody as the original naive B cell, or the “parent B cell”. Plasma B cells produce the same antibody as the parent B cell, but they aren’t membrane bound. Instead, plasma B cells can secrete antibodies. Secreted antibodies work to identify free pathogens that are circulating throughout the body. When the naive B cell divides and differentiates, both plasma cells and memory B cells are made.
B cells also express a specialized receptor, called the B cell receptor (BCR). B cell receptors assist with antigen binding, as well as internalization and processing of the antigen. B cell receptors also play an important role in signaling pathways. After the antigen is internalized and processed, the B cell can initiate signaling pathways, such as cytokine release, 7 to communicate with other cells of the immune system. For more information on cell signalling, check out this article on cell-to-cell communication.
Once formed in the bone marrow, T progenitor cells migrate to the thymus (hence the name “T cell”) to mature and become T cells. While in the thymus, the developing T cells start to express T cell receptors (TCRs) and other receptors called CD4 and CD8 receptors. All T cells express T cell receptors, and either CD4 or CD8, not both. So, some T cells will express CD4, and others will express CD8.
Unlike antibodies, which can bind to antigens directly, T cell receptors can only recognize antigens that are bound to certain receptor molecules, called Major Histocompatibility Complex class 1 (MHCI) and class 2 (MHCII). These MHC molecules are membrane-bound surface receptors on antigen-presenting cells, like dendritic cells and macrophages. CD4 and CD8 play a role in T cell recognition and activation by binding to either MHCI or MHCII.
Macrophage binding to T cell
T cell receptors have to undergo a process called rearrangement, causing the nearly limitless recombination of a gene that expresses T cell receptors. The process of rearrangement allows for a lot of binding diversity. This diversity could potentially lead to accidental attacks against self cells and molecules because some rearrangement configurations can accidentally mimic a person’s self molecules and proteins. Mature T cells should recognize only foreign antigens combined with self-MHC molecules in order to mount an appropriate immune response.
T cell positive selection and negative selection
In order to make sure T cells will perform properly once they have matured and have been released from the thymus, they undergo two selection processes:
- Positive selection ensures MHC restriction by testing the ability of MHCI and MHCII to distinguish between self and nonself proteins. In order to pass the positive selection process, cells must be capable of binding only self-MHC molecules. If these cells bind nonself molecules instead of self-MHC molecules, they fail the positive selection process and are eliminated by apoptosis.
- Negative selection tests for self tolerance. Negative selection tests the binding capabilities of CD4 and CD8 specifically. The ideal example of self tolerance is when a T cell will only bind to self-MHC molecules presenting a foreign antigen. If a T cell binds, via CD4 or CD8, a self-MHC molecule that isn’t presenting an antigen, or a self-MHC molecule that presenting a self-antigen, it will fail negative selection and be eliminated by apoptosis.
These two selection processes are put into place to protect your own cells and tissues against your own immune response. Without these selection processes, autoimmune diseases would be much more common.
T cell positive selection and negative selection process
After positive and negative selection, we are left with three types of mature T cells: Helper T cells (T cells), Cytotoxic T cells (T cells), and T regulatory cells (T cells).
- Helper T cells express CD4, and help with the activation of T cells, B cells, and other immune cells.
- Cytotoxic T cells express CD8, and are responsible for removing pathogens and infected host cells.
- T regulatory cells express CD4 and another receptor, called CD25. T regulatory cells help distinguish between self and nonself molecules, and by doing so, reduce the risk of autoimmune diseases.
Helper T cell, Cytotoxic T cell, T regulatory cell diagrams
Humoral vs. Cell Mediated Immunity
Immunity refers to the ability of your immune system to defend against infection and disease. There are two types of immunity that the adaptive immune system provides, and they are dependent on the functions of B and T cells, as described above.
Humoral immunity is immunity from serum antibodies produced by plasma cells. More specifically, someone who has never been exposed to a specific disease can gain humoral immunity through administration of antibodies from someone who has been exposed, and survived the same disease. “Humoral” refers to the bodily fluids where these free-floating serum antibodies bind to antigens and assist with elimination.
Cell-mediated immunity can be acquired through T cells from someone who is immune to the target disease or infection. “Cell-mediated” refers to the fact that the response is carried out by cytotoxic cells. Much like humoral immunity, someone who has not been exposed to a specific disease can gain cell-mediated immunity through the administration of T and T cells from someone that has been exposed, and survived the same disease. The T cells act to activate other immune cells, while the T cells assist with the elimination of pathogens and infected host cells.
Because the adaptive immune system can learn and remember specific pathogens, it can provide long-lasting defense and protection against recurrent infections. When the adaptive immune system is exposed to a new threat, the specifics of the antigen are memorized so we are prevented from getting the disease again. The concept of immune memory is due to the body’s ability to make antibodies against different pathogens.
A good example of immunological memory is shown in vaccinations. A vaccination against a virus can be made using either active, but weakened or attenuated virus, or using specific parts of the virus that are not active. Both attenuated whole virus and virus particles cannot actually cause an active infection. Instead, they mimic the presence of an active virus in order to cause an immune response, even though there are no real threats present. By getting a vaccination, you are exposing your body to the antigen required to produce antibodies specific to that virus, and acquire a memory of the virus, without experiencing illness.
Some breakdowns in the immunological memory system can lead to autoimmune diseases. Molecular mimicry of a self‐antigen by an infectious pathogen, such as bacteria and viruses, may trigger autoimmune disease due to a cross-reactive immune response against the infection. One example of an organism that uses molecular mimicry to hide from immunological defenses is Streptococcus infection.
Innate Immunity vs. Adaptive Immunity: A summary
The following chart compares and summarizes all of the important parts of each immune system:
|Attribute||Innate Immunity||Adaptive Immunity|
|Response Time||Fast: minutes or hours||Slow: days|
|Specificity||Only specific for molecules and molecular patterns associated with general pathogens or foreign particles||Highly specific! Can discriminate between pathogen vs. non-pathogen structures, and miniscule differences in molecular structures|
|Major Cell Types||Macrophages, Neutrophils, Natural Killer Cells, Dendritic Cells, Basophils, Eosinophils||T cells, B cells, and other antigen presenting cells|
|Key Components||Antimicrobial peptides and proteins, such as toxic granules||Antibodies|
|Self vs. Nonself Discrimination||Innate immunity is based on self vs. nonself discrimination, so it has to be perfect||Not as good as the innate immune system, but still pretty good at determining which is which. Problems in self vs. nonself discrimination result in autoimmune diseases|
|Immunological Memory||None||Memory used can lead to faster response to recurrent or subsequent infections|
|Diversity and Customization||Limited: Receptors used are standard and only recognize antigen patterns. No new receptors are made to adapt the immune response||Highly diverse: can be customized by genetic recombination to recognize epitopes and antigenic determinants.|
Want to join the conversation?
- B cells are not so called because of the fact that they formed in the bone marrow. The name is attributed to the discovery of these lymphocytes in an organ known as bursa of fabricius found in birds. Read the awesome story of how these cells were discovered here:
- That is true, but it's nice to use "B" to remember "bone marrow", as you would for "T" for "thymus", since humans don't have a bursa of fabricus.(78 votes)
- Why is it important for us to have specific immune system? I mean that what are the benefits of being "specific"?(1 vote)
- Imagine if your soccer team had a weak defense, they would get scored on and lose every game. For humans, our immunity can be thought of as our "defense" to the world. If humans had a weak defense, we would get infected with microbes. Thus, it is important to have a strong defense.
In soccer each team shall field 11 players on the field at one time, for a total of 22 players. This makes playing defense manageable. Yet, our immune system plays defense against millions of microbes. How do you create a defense that defends against that many different microbes?
Adaptive immunity and genetics.
Adaptive immunity is important because it provides us with an everlasting defense system that can be used against new and varying microbes. The mechanism by which our adaptive immune system defends against microbes suggests that genetics plays a sacrosanct role in immunity.
For example, in humoral immunity, hypermutation ("many mutations") of the antigen-binding site of antibodies results in varying affinities of antibodies for a specific microbe.
Similarly, in cell-mediated immunity, hypermutation ("many mutations") of a helper T-cell receptor results in varying affinities of a specific antigen presented on MHC I & II molecules.
Here is another reason why the adaptive immune system is important. Currently, researchers have tried to modify the hypermutation regions in attempt to increase the affinity for cancer cells. As a result, the new, genetically-modifed T-cells, would attack the cancer cells more effectively. Also, sometimes cancer cells like to "hide" from the immune system, so by sampling the cancer cells and reprogramming the T-cells, we can try to "uncover" the hiding cancer cells.
Adaptive immunity = specific immunity
Adaptive immunity = humoral + cell-mediated immunity
Humoral immunity = (B cells)
Cell-mediated immunity = (T cells)
antigen = microbe = "criminal"
antibody = receptor = "cop"(13 votes)
- from the picture above immature Tcell have both CD4 and CD8 ?
I thought that they can be only CD4 or CD8...(2 votes)
- Early in their development (after they have rearranged their receptor), they are "double positive" meaning that they have both CD4 and CD8 receptors. Then they test their receptor on dendritic cells MHC. If they are able to bind they are positively selected (they get a survival signal) and the hypothesis is that if it's a TCR with a CD4 receptor it becomes a CD4+ cell, and if it's a TCR with a CD8 receptor it becomes a CD8+ cell. But this is before they are let out in the blood stream, there they are CD4+ or CD8+(3 votes)
- In the section Humoral vs cell mediated immunity, they talk about how a person can acquire cell mediated immunity from T cells of someone else infected. How is this possible when T cells undergo positive selection for self MHC?(3 votes)
- For positive selection, why would we want the T cells to only bind self MHC molecules? Does that mean that if the naive T cells were to bind random antigens lacking either of the MHC molecules, they effectively would not be able to do their job because of lack of "recognition and activation"?(2 votes)
- about T cells, it says Unlike antibodies, which can bind to antigens directly, T cell receptors can only recognize antigens that are bound to certain receptor molecules, called Major Histocompatibility Complex class 1 (MHCI) and class 2 (MHCII). These MHC molecules are membrane-bound surface receptors on antigen-presenting cells, like dendritic cells and macrophages.
but then later it says that
T cell receptors have to undergo a process called rearrangement, causing the nearly limitless recombination of a gene that expresses antibodies.
so do T cells make antibodies or not? and for which receptrs do the T cells do rearrangement for? TCR? CD8? CD4?(2 votes)
- i am not getting about the what are the major cell involve in the innate and accuired immunity ... there are also natural acquired passive immunity which are not mention in this slide.... please clear my question(2 votes)
- I was led to believe B cells can recognize antigens without helper T cells, however they become activated after interacting with a T cell for the same antigen (the double handshake). The idea was the system was predicated on both cells recognizing an antigen to decrease the likelihood one or the other would be triggered incorrectly.(1 vote)
- That is correct. The B-cell can't do much if it's not stimulated by a T-cell. A minor reaction can happen, but it's weak and no memory cells are created.(2 votes)
- To the person who wrote this article! Thanks for the information, it really helped a lot!
But There are many points throughout this informative article that contradict each other, such as when you mention differentiation you said it becomes EITHER a memory b-cell or a plasma cell, but in the following paragraph or two you said differentiation results in both.
Regardless, great work!(1 vote)