How does the immune system get rid of foreign substances and microbes?1, 2
When microbes, foreign substances, pollen, or other allergens enter or attempt to enter the body, the immune system works to expel them. The first line of defense against diseases and allergies includes physical barriers, such as skin, mucosal linings, stomach acid, and mucus. These defenses prevent many but not all invasions of the body. Some of these substances are expelled by coughing or sneezing, but others face a complex immune system response.
Several types of immune system cells are found in the blood (via the circulatory system) and lymph (via the lymphatic system, which drains fluids from tissues). These cells work together to fight off foreign substances and microbes (collectively called antigens) – the response to allergens is a bit different and is not discussed here. Some of these cells are “non-specific,” as they attack any antigen. Other cells are highly specialized to target and kill specific antigens.
- The non-specific cells include phagocytes, mast cells, eosinophils, and natural killer cells.
- The cells that target specific antigens include B- and T-lymphocytes (or B-cells and T-cells).
- In addition to non-specific and specific cells, the immune system relies on different types of proteins. Proteins are complex, natural substances that have a certain chemical structure. They facilitate important functions in the body and include hormones, antibodies, immunoglobulins, complement, and enzymes.
The non-specific response. The non-specific immune system cells circulate in the blood or tissues. When an antigen is encountered, certain types of cells ingest it. Phagocytes attack the smaller antigens by engulfing them – macrophages attack viruses and neutrophils attack bacteria. Other non-specific cells target larger antigens, such as worms, yeast, and fungal infections.
- Macrophages “present” or display a portion of antigen on their surface, so that it can be recognized as a foreign body by the T-cells, which prompts the T-cells to act.
- In addition to possible ingestion by the non-specific cells, antigens are faced with the prospect of encountering antibodies that circulate in the blood and lymph. These antibodies bind to the surface of the antigen, which alerts other cells and proteins in the immune system to the antigen’s presence.
- Another component of the immune system that recognizes the antibody bound to the surface of the antigen is a group of proteins called “complement.” When the complement proteins recognize the antibodies bound to the surface of an antigen, they embark on a series of steps to destroy the antigen. In addition, the complement proteins work with the B-cells, which produce immunoglobulins that help to destroy the antigen.
- Natural killer cells focus on distinguishing “self” (the body’s own cells) from “non-self.” When they encounter cells that they do not recognize as “self,” they kill them.
The specific antigen response. In some cases, the non-specific response is able to effectively combat the antigen. In other cases, some antigens survive the initial non-specific response; ridding the body of these infections requires the use of an alternative strategy – a response that is targeted to that particular antigen.
B- and T-cells circulate through the body via blood vessels and the lymphatic system, and congregate in the lymph nodes. During an infection, the B- and T-cells – alerted by the antibodies and macrophages during the non-specific response – recognize the presence of antigen. Although both B- and T-cells target specific antigens, they act in different ways.
- B-cells form plasma cells, which produce specific antibodies that can attach to the antigen’s outer proteins. The antigen binds to an antibody and, with the assistance of T-helper cells, is pulled inside the B-cell, where it is disassembled.
- Because different types of antigens have different outer proteins that vary in size, structure, and shape, producing an antibody that perfectly matches the antigen’s proteins is an iterative process.
- Once the best match is found, the focus turns to producing high numbers of that specific antibody, which then circulate in blood and lymph to find and destroy the antigen.
- The B-cell-associated process is called the immune system’s humoral response.
- Unlike the B-cells that produce many types of specific antibodies, the T-cell response involves producing cells that are specific to the antigen.
There are several types of T-cells. T-cytotoxic cells kill B-cells and macrophages that have ingested antigen. T-memory cells “remember” the past antigen exposures, which leads to more rapid production of T-cytotoxic cells that are able to destroy an antigen. T-helper cells serve several functions, including activating B-cells that have bound antigen so that the B-cell can ingest the antigen and producing a growth factor that signals the need for more B- and T-cells. T-helper cells play a key role by coordinating the immune system’s humoral and cell-mediated (T-cell) responses.
- T-memory and T-helper cells work together to ensure that the “correct” T-cytotoxic cells are produced, i.e., cells that have receptors on their surface that can bind to the specific outer proteins on the antigen.
- For example, T-cytotoxic cells for HIV have different receptors compared to T-cytotoxic cells for tuberculosis.
- As with the B-cell antibody production, figuring out which T-cytotoxic cells to produce is an iterative process.
- When T-cytotoxic cells encounter macrophages or B-cells that have ingested an antigen, they are activated, bind to the cells, and kill the cells and antigen.
- T-cytotoxic cells have the protein CD8 on their surface; T-helper cells have the CD4 protein. These proteins are used to count the number of cells in a volume of blood. For example, normal CD4 count is 500 – 1500 per cubic millimeter; AIDS is diagnosed as less than 200 CD4 cells per cubic millimeter.
- The T-cell process is called the immune system’s cell-mediated response.
The humoral and cell-mediated responses are slower when a person is first exposed to an antigen than for a subsequent exposure. This is because, with the first exposure, B-cells and T-cells have to go through the iterative process to find the best match of antibody and surface receptor, respectively. After this process, antigen and antibody information is stored in the immune system’s “memory” cells. Thus, with subsequent response, the B- and T–cells do not have to find the best match – they can proceed to developing antibodies and cells that are the best match for the antigen.
Example: The Immune System’s Defense Against Viruses3The following example shows what happens to an invading virus. These seven steps include the non-specific phase (steps 1 – 2) and the B-cell and T-cell response (steps 3 – 7).
 Courtesy of: Shannan Muskopf | website
How do viruses work?1, 2
Viruses are small microbes that use a host body’s system for energy and self-replication. They enter the body through the mouth, digestive tract, respiratory system, breaks in the skin (via cuts or needle injection), or the anal/genital tract.
Viruses are relatively simple structures. They have an outer coat made of protein and inside they have genetic material (a genome), composed of either DNA or RNA. The viral genetic material encodes proteins needed to replicate, assemble, and released new virus particles. In addition to genetic material, they may have various proteins inside their capsule, including enzymes that are needed for viral replication. Viruses cannot reproduce on their own – they need to use parts of the host cell to produce new copies.
For DNA viruses:
- Once in the host’s body, viruses locate specific host cell types, bind to the receptor sites (proteins) on the surface of the host cell, and are drawn into the cell (called adsorption and penetration).
- As they penetrate the host cells, the outer protein coat is lost (called uncoating), while the viral DNA and proteins (including virus enzymes) enter inside the host cell.
- Inside the host cell, multiple copies of the viral DNA are made (called replication). The DNA encodes new viral proteins that are needed to assemble new virus particles.
- In order to make new virus particles, the information in the DNA is transcribed into messenger RNA (mRNA) in a process called transcription.
- The new mRNA contains instructions to produce viral proteins – both the new internal proteins and the outer coat proteins. The process of generating protein from mRNA is called translation.
- The new internal and outer coat proteins combine to form new viruses (called assembly).
- After the assembly process, the viral particles become mature viruses (called maturation) and are released from the cell (called budding). These new viruses can infect other host cells. Sometimes host cells are destroyed in the process of viral release; in other instances, such as HIV, viruses use some host cells as carriers or factories, keeping them alive in order to produce more copies of the virus.
The Replication Cycle of Smallpox4
Smallpox (the dark green squares in the image below) is a DNA virus that uses the process described above to make multiple copies of itself. In addition to DNA, the smallpox virus contains more than 100 proteins and 10 viral enzymes that are used in the DNA replication process.
 Courtesy of: Karl Harrison, University of Oxford | website
For RNA viruses:
Some viruses (retroviruses) contain RNA rather than DNA. For these retroviruses, the basic process of producing new viral particles – binding and penetrating the cell, using the host cell structure to make copies of the virus, and assembling and releasing the new viruses – is similar to the process for DNA viruses. However, there are a few differences.
- After binding to the host cell receptor, the outer viral envelope is lost, but the protein coat remains intact until the virus is in the host cell, when it is also lost.
- The virus contains proteins – in particular, an enzyme called reverse transcriptase – that allow viral DNA to be produced from viral RNA in a process called reverse transcription.
- The viral DNA is incorporated into the host’s DNA (called integration), using a viral enzyme called integrase. Incorporation into the host’s DNA makes it easier for the virus to use the host cell as a carrier, which can be reactivated at a later time to produce more copies of the virus. The virus in the carrier cells can remain latent for a long period of time, resulting in a relatively low viral load in blood.
- DNA is then transcribed into viral RNA, which is translated into protein.
- The new viruses are assembled and leave the cell as immature virus particles. In some cases, the host cells are destroyed when the virus leaves the cell, but in other cases the host cell becomes a carrier.
- With activation of a viral enzyme, the particles become mature viruses. This last step is necessary for the virus to infect other cells.
The Replication Cycle of HIV5
HIV is an RNA virus (or retrovirus). It uses a combination of destroying cells in the process of replication and retaining a latent infection in carrier cells.
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Steps in Replication5
- Binding – virus attaches to host cell
- Reverse Transcription – viral RNA produced from viral DNA
- Integration – viral DNA incorporated into host DNA
- Transcription – viral DNA into viral RNA
- Translation – viral RNA into viral proteins
- Viral Assembly – internal and outer coat proteins combine to create new virus particles
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Courtesy of: AIDSmeds.com |
Both DNA and RNA viruses are common. Although DNA is more stable than RNA, both DNA and RNA viruses can develop mutations – small changes in their genetic material. The impact of these mutations varies. Mutations in relatively unused regions of the genome or that do not significantly change the structure of the protein encoded by the gene have little impact. Mutations that significantly alter key proteins can increase the virus’ ability to elude the immune system and decrease responsiveness to drugs or vaccines.
Influenza, for example, is highly mutable and the strains causing seasonal flu vary from year to year and place to place – thus a new vaccination is required every year. Other viruses, such as chicken pox and measles, are relatively stable and vaccines and medications have been effective for many years.
Examples of Viruses and the Diseases They Cause
| DNA |
RNA |
| Viruses |
Disease |
Viruses |
Disease |
| Herpes simplex virus-1 |
Meningoencephalitis |
Hantavirus |
Endemic hemorrhagic fever; Korean hemorrhagic fever |
| Herpes simplex virus-2 |
Genital herpes |
Human immunodeficiency virus |
HIV/AIDS |
| Herpesvirus-4: Epstein-Barr |
Mononucleosis |
Influenza |
Influenza |
| Herpesvirus-3: Varicella |
Chicken pox |
Poliovirus |
Poliomyelitis |
| Human papillomavirus (HPV) |
Genital warts |
Lyssavirus |
Rabies |
| Variola virus |
Smallpox |
Rubivirus |
Rubella |
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