THE
ADAPTIVE IMMUNE SYSTEM
II.
HUMORAL IMMUNITY
SARS-CoV-2 NUCLEIC ACID VACCINES
Fundamental Statements for this Learning Object:
1. In the case of the two mRNA vaccines licensed for use in this country (Pfizer and Moderna), mRNA molecules coding for a piece of the spike protein (S protein) of SARS-CoV-2 are enclosed in lipid nanoparticles. The lipid nanoparticle coating protects the mRNA molecules from being broken down by enzymes within the body.
2. The spike or S protein is what enables the virus to bind to a host receptor molecules called human ACE-2 enzyme (angiotensin-converting enzyme 2) that are highly expressed on a variety of human cells, including cells in the nose, throat, lungs, intestines, kidneys, and heart. The virus must tightly bind to this ACE-2 molecule before it can subsequently enter the host cell and replicate.
3. The lipid nanoparticles also helps the mRNA enter antigen-presenting dendritic cells located in the lymph node near the vaccination site. These dendritic cells play a crucial role in initiating an adaptive immune response against SARS-CoV-2.
4. One drawback to mRNA vaccines, however, is that mRNA becomes degraded at high temperatures. This is why the current vaccines have to be stored at very cold temperatures.
5. Injection of the vaccine into the muscle triggers the production of antigenic SARS-CoV-2 spike proteins by muscle cells at the site of injection.
6. The mRNA-containing lipid nanoparticles at the injection site fuse with the plasma membrane of the muscle cells emptying their mRNA molecules into the cytosol of the cell which then bind to host cell ribosomes where they are then translated into molecules of the SARS-CoV-2 spike protein. Some of these spike proteins pass through cellular organelles called proteasomes where they are degraded into a series of viral peptides. These peptides are then transported into the rough endoplasmic reticulum (ER) where they then bind to the grooves of newly synthesized immunity molecules called MHC-I molecules, which are transported to the plasma membrane of the host cell where they become anchored. Here, the peptide and MHC-I/peptide complexes can be recognized by cytotoxic T-lymphocytes or CTLs. This illustrates that the vaccine stimulates cell-mediated immunity similar to when cells are infected by living SARS-CoV-2.
7. Some of the vaccine then drains into lymph nodes near the injection site where it is taken up by antigen-presenting dendritic cells in the lymph nodes. In addition, spike protein produced by muscle cells at the injection site also drain into the lymph nodes where dendritic cells take them up by endocytosis. As with the muscle cells, the viral mRNAs from the lipid nanoparticles bind to dendritic cell ribosomes where they are then translated into molecules of the SARS-CoV-2 spike protein, some of which pass through cellular organelles called proteasomes where they are degraded into a series of viral peptides. These peptides are then transported into the rough endoplasmic reticulum (ER) where they then bind to MHC-1 molecules. These MHC-I/peptide complexes are, in turn, transported to the plasma membrane of the host cell where they can be recognized by naive T8-lymphocytes by way of their T-cell receptors (TCRs) and CD8 molecules. This enables those naive T8-lymphocyte to become activated, proliferate, and differentiate into cytotoxic T-lymphocytes or CTLs which bind to infected cells displaying those same SARS-CoV-2 viral peptides and kill those infected cells.
8. The dendritic cells also take up previously synthesized spike proteins by endocytosis where they are then degraded into viral peptides. The endoplasmic reticulum of dendritic cells also produces immunity molecules called MHC-II molecules which are then transported to the Golgi apparatus. From the Golgi apparatus the MHC-II molecules are transported to endosomes where they bind to viral peptides from the S-protein within the endosome. From here, the MHC-II/peptide complexes are transported to the plasma membrane of the dendritic cell where they become anchored. The MHC-II/peptide complexes can now be recognized by naive T4-lymphocytes by way of their T-cell receptors (TCRs) and CD4 molecules having a complementary shape. This enables those T4-lymphocyte to become activated, proliferate, and differentiate into various T4 helper lymphocytes that regulate immunity through the cytokines they produce.
9. The antigenic spike proteins (S-proteins) cause the immune system to begin producing antibodies that are able to bind to the S-protein of SARS-CoV-2, as well as activating T4-lymphocytes and T8-lymphocytes to fight off the infection. Thus, the vaccines induce not only humoral immunity (the production of antibodies to neutralize the virus), but also cell-mediated immunity (the production of cytotoxic T-lymphocytes that kill virus-infected cells).
10. B-lymphocytes, after interacting with effector T4-helper cells, proliferate and differentiate into plasma cells that secrete antibodies that specifically bind to the S-protein of SARS-CoV-2. The binding of the antibodies to the S-protein neutralizes the virus by preventing it from binding to the ACE-2 receptors on human cells, entering the cell, and replicating.
11. Once naive T4-lymphocytes are activated by dendritic cells, they proliferate and differentiate into T4-effector lymphocytes that regulate the immune responses by way of the cytokines they produce. These cytokines collectively are involved in activating or deactivating or enhancing or suppressing virtually every aspect of the body's innate and adaptive immune responses.
12. Virus-infected cells also process viral S-protein (by way of proteasomes) into viral peptides that bind to MHC-I molecules and are transported to the surface of the infected cell. Here, the peptide and MHC-I/peptide complexes can be recognized by cytotoxic T-lymphocytes or CTLs which bind to infected cells displaying those same SARS-CoV-2 viral peptides by way of their T-cell receptors (TCRs) and CD8 molecules. The CTLs then kill the infected cell to which it has bound by apoptosis, a programmed cell death.
13. Unlike the mRNA vaccines for SARS-Co-V-2 which use lipid nanoparticles to deliver mRNA coding for the spike or S-protein into human cells, the Johnson and Johnson-Jenssen vaccine has added a DNA gene coding for the spike protein of SARS-CoV-2 to another virus called Adenovirus 26. Adenoviruses are a group of viruses that typically cause colds or flu-like symptoms, but Adenovirus 26 has been modified so that the virus can enter human cells but cannot replicate within them or cause illness. The DNA gene coding for the spike protein is eventually transcribed into mRNA and translated by host cell ribosomes into viral spike proteins.
LEARNING
OBJECTIVES FOR THIS SECTION
A. Pfizer and Moderna mRNA Vaccines for SARS-CoV-2
mRNA vaccines contain strands of messenger RNA (mRNA) wrapped in lipid nanoparticles. In the case of the two mRNA vaccines licensed for use in this country (Pfizer and Moderna), the mRNA molecules enclosed in the lipid nanoparticles code for a piece of the spike protein (S protein) of SARS-CoV-2, the viral protein that enables the virus to bind to a host receptor molecules called human ACE-2 enzyme (angiotensin-converting enzyme 2) (def) that are highly expressed on a variety of human cells, including cells in the nose, throat, lungs, intestines, kidneys, and heart. The virus must tightly bind to this ACE-2 molecule before it can subsequently enter the host cell and replicate (see Fig. 1). Since only part of the spike protein is made from the vaccine, it does no harm to the person vaccinated but it is antigenic (def).
The lipid nanoparticle coating protects the mRNA molecules from being broken down by enzymes within the body. They also helps the mRNA enter antigen-presenting cells (APCs) (def) such as dendritic cells located in the lymph node near the vaccination site. These APCs play a crucial role in initiating an adaptive immune response against SARS-CoV-2. One drawback to mRNA vaccines, however, is that mRNA becomes degraded at high temperatures. This is why the current vaccines have to be stored at very cold temperatures. (Pfizer's SARS-CoV-2 vaccine has to be stored at -70 degrees Celsius [-94 degrees Fahrenheit], and the Moderna vaccine at -20 C [-4 F].)
B. Mechanism of Action: Induction of Immunity
1. Background Information from Unit 6: Adaptive Immunity
a. The MHC pathways
MHC molecules enable T-lymphocytes (def) to recognize epitopes (def) of antigens (def) and discriminate self from non-self.
1. MHC-I pathway
MHC-I molecules (def) are made by all nucleated cells in the body and are designed to enable the body to recognize infected cells and tumor cells and destroy them with cytotoxic T-lymphocytes or CTLs (def). CTLs are effector (def) defense cells derived from naive T8-lymphocytes (def). During the replication of viruses and intracellular bacteria within their host cell, as well as during the replication of tumor cells, viral, bacterial, or tumor proteins are degraded into a variety of peptide (def) epitopes by cylindrical organelles called proteasomes (def). These peptide epitopes (def) are then attached to a groove of MHC-I molecules that are then transported to the surface of that cell where they can be recognized by a complementary-shaped T-cell receptor (TCR) (def) and a CD8 molecule (def), a co-receptor found on the surface of both naive T8-lymphocytes and cytotoxic T-lymphocytes (CTLs).
2. MHC-II pathway
MHC-II molecules (def), made by antigen-presenting (APCs) (def) such as dendritic cells (def), macrophages (def), and B-lymphocytes (def), are designed to enable T4-lymphocytes to recognize epitopes of antigens and discriminate self from non-self. The antigens are engulfed and placed in a phagosome (endosome) (def) which then fuses with lysosomes (def) where proteases within the phagolysosome enabling protein antigens to be degraded into a series of short peptides. These peptide epitopes (def) are then attached to MHC-II molecules and are then transported to the surface of the antigen-presenting cell. Here the MHC-II molecules with bound peptides can be recognized by a complementary-shaped T-cell receptor (TCR) (def) and a CD4 molecule (def), a co-receptor found on the surface of naive T4-lymphocytes (def) and effector T4-helper lymphocytes (def). T4-lymphocytes are the cells the body use to regulate both humoral immunity (def) and cell-mediated immunity (def).
b. Antigen-presenting dendritic cells
Most dendritic cells (def) are derived from monocytes and are referred to as myeloid dendritic cells. They are located under the surface epithelium of the skin and the surface epithelium of the mucous membranes of the respiratory tract, genitourinary tract, and the gastrointestinal tract. They are also found throughout the body's lymphoid tissues and in most solid organs. Upon capturing antigens through pinocytosis and phagocytosis (endocytosis) , the dendritic cells detach from their initial site, enter lymph vessels, and are carried to regional lymph nodes. By the time the dendritic cells enter the lymph nodes, they have matured and are now able to present peptide epitopes to the ever-changing populations of naive T8-lymphocytes (def) and naive T4-lymphocytes (def) located in the T-cell area of the lymph nodes. Dendritic cells produce both MHC-I molecules (def), which they use to present peptides from protein antigens to T8-lymphocytes, and MHC-II molecules (def), which they use to present peptides from protein antigens to T4-lymphocytes.
c. T4-lymphocytes (T4-cells)
The primary role of T4-lymphocytes (def) is to regulate the body's immune responses through the production of regulatory molecules called cytokines (def). Once naive T4-lymphocytes (def) are activated by dendritic cells (def), they proliferate and differentiate into T4-effector lymphocytes (def) that regulate the immune responses by way of the cytokines they produce. T4-lymphocytes are T-lymphocytes displaying surface molecules called CD4 molecules (def). They also have on their surface, epitope receptors called T-cell receptors (def) or TCRs that, in cooperation with the CD4 molecules, have a shape capable of recognizing peptides (def) from protein antigens bound to MHC-II molecules (def) on the surface of antigen-presenting cells (APCs) (def) such as dendritic cells (def), macrophages (def), and B-lymphocytes (def). The TCR recognizes the peptide while the CD4 molecule recognizes the MHC-II molecule. During its development, each T4-lymphocyte becomes genetically programmed, by gene-splicing reactions similar to those in B-lymphocytes and T4-lymphocytes, to produce a TCR with a unique shape capable of binding a specific peptide/MHC-II complex with a corresponding shape.
d. T8-lymphocytes (T4-cells)
The primary role of T8-lymphocytes (def) is to kill infected cells and tumor cells by inducing apoptosis (def) of those cells. Once naive T8-lymphocytes (def) are activated by dendritic cells (def), they proliferate and differentiate into T8-effector lymphocytes (def) called cytotoxic T-lymphocytes (CTLs) (def) at bind to and kill infected cells and tumor cells by a process called apoptosis. T8-lymphocytes are T-lymphocytes displaying a surface molecule called CD8 (def). T8-lymphocytes also have on their surface, T-cell receptors or TCRs (def) similar to those on T4-lymphocytes. The TCR on T8-lymphocytes, in cooperation with CD8, bind peptides from protein antigens bound to MHC-I molecules (def). The TCR recognizes the peptide while the CD8 molecule recognizes the MHC-I molecule. During its development, each T8-lymphocyte becomes genetically programmed, by gene-splicing reactions similar to those in B-lymphocytes and T4-lymphocytes, to produce a TCR with a unique shape capable of binding a specific peptide/MHC-I complex with a corresponding shape.
e. B-lymphocytes (B-cells)
B-lymphocytes (def) are responsible for the production of antibody molecules (def) during adaptive immunity. Antibodies are critical in removing extracellular microorganisms and toxins. During its development, each B-lymphocyte becomes genetically programmed through a series of gene-splicing reactions to produce an antibody molecule with a unique specificity - a specific 3-dimensional shape capable of binding a specific epitope (def) of an antigen (def). Many molecules of that antibody are placed on the surface of the B-lymphocyte where they can function as B-cell receptors (def) capable of binding specific epitopes of a corresponding shape found on antigens. In order for naive B-lymphocytes (def) to proliferate, differentiate, and mount an antibody response against most protein antigens, they must interact with effector T4-lymphocytes (def) called TFH cells (def) which collectively produce cytokines that enable activated B-lymphocytes to proliferate, stimulate the B-lymphocytes to synthesize and secrete antibodies, promote the differentiation of B-lymphocytes into antibody-secreting plasma cells (def), and enable antibody producing cells to switch the class or isotype (def) of antibodies being produced.
2. How the Vaccine Stimulates Immunity in Muscle Cells at the Injection Site
Injection of the vaccine into the muscle triggers the production of antigenic (def) SARS-CoV-2 spike proteins by muscle cells at the site of injection, stimulating both humoral (def) and cell-mediated immunity (def) .
First, the mRNA-containing lipid nanoparticles at the injection site fuse with the plasma membrane of the muscle cells emptying their mRNA molecules into the cytosol of the cell. (See Fig. 2, Step 1.)
The viral mRNAs released from the lipid nanoparticles bind to host cell ribosomes where they are then translated into molecules of the SARS-CoV-2 spike protein. (See Fig. 2, Step 2.)
Some of these spike proteins pass through cellular organelles called proteasomes (def) where they are degraded into a series of viral peptides (def) . (See Fig. 2, Step 3.)
These peptides are then transported into the rough endoplasmic reticulum (ER) where they then bind to the grooves of newly synthesized immunity molecules called MHC-I molecules (def) . (See Fig. 2, Step 4.).
The endoplasmic reticulum then transports the MHC-I molecules with bound viral peptides to the Golgi apparatus. (See Fig. 2, Step 5.)
The Golgi apparatus, in turn, transports the MHC-I/peptide complexes by way of an exocytic vesicle to the plasma membrane of the host cell where they become anchored. (See Fig. 2, Step 6.) Here, the peptide and MHC-I/peptide complexes can be recognized by cytotoxic T-lymphocytes or CTLs (def).This illustrates that the vaccine stimulates cell-mediated immunity similar to when cells are infected by living SARS-CoV-2.
Some of the spike proteins synthesized within the cell migrate to the surface of the cell where they become embedded. Others are secreted by the cell where they drain into lymph nodes near the injection site (See Fig. 2, Step 7.). These spike proteins function as antigens (def) that can be recognized by the B-cell receptor (BCR) (def) of naive B-lymphocytes (B-cells) (def) . (See Fig. 4.) This enables those naive B-lymphocyte to become activated, proliferate, and differentiate into antibody secreting plasma cells (def) .
Some of the vaccine then drains into area lymph nodes near the injection site where it is taken up by antigen-presenting cells (APCs) (def) called dendritic cells (def) in the lymph nodes. In addition, when vaccinated cells die, the cellular debris will contain many spike proteins and spike protein fragments, which can also be taken up by antigen-presenting cells such as dendritic cells, macrophages (def) , and B-lymphocytes (def) .
The mRNA from the vaccine is eventually destroyed by the cell, leaving no permanent trace.
3. How the Vaccine Stimulates Immunity in Antigen Presenting Dendritic Cells
As mentioned above, the vaccine triggers the production of antigenic (def) SARS-CoV-2 spike proteins by muscle cells at the site of injection. Some of the vaccine then drains into lymph nodes near the injection site where it is taken up by antigen-presenting cells (APCs) (def) called dendritic cells (def) in the lymph nodes. In addition, when vaccinated cells die, the debris will contain many spike proteins and spike protein fragments, which can also be taken up by antigen-presenting cells such as dendritic cells, macrophages (def) , and B-lymphocytes (def) .
The role of antigen-presenting dendritic cells in inducing immunity against SARS-CoV-2 is shown in Fig. 5. and the following text below.
The mRNA-containing lipid nanoparticles which have drained into the regional lymph nodes from the injection site fuse with the plasma membrane of the dendritic cells (def) emptying their mRNA molecules into the cytosol of the cell. (See Fig. 5, Step 1.) In addition, spike protein produced by muscle cells at the injection site also drain into the lymph nodes where dendritic cells take them up by endocytosis. (See Fig. 5, Step 8.)
The viral mRNAs from the lipid nanoparticles bind to host cell ribosomes where they are then translated into molecules of the SARS-CoV-2 spike protein. (See Fig. 5, Step 2.)
Some of these spike proteins pass through cellular organelles called proteasomes (def) where they are degraded into a series of viral peptides (def) . (See Fig. 5, Step 3.)
These peptides are then transported into the rough endoplasmic reticulum (ER) where they then bind to the grooves of newly synthesized immunity molecules called MHC-1 molecules (def) . (See Fig. 5, Step 4.).
The endoplasmic reticulum then transports the MHC-I molecules with bound viral peptides to the Golgi apparatus. (See Fig. 5, Step 5.)
The Golgi apparatus, in turn, transports the MHC-I/peptide complexes by way of an exocytic vesicle to the plasma membrane of the host cell where they become anchored. (See Fig. 5, Step 6.) Here, the peptide and MHC-I/peptide complexes can be recognized by naive T8-lymphocytes (def) by way of their T-cell receptors (TCRs) (def) and CD8 molecules (def) having a complementary shape. (See Fig. 3.) This enables those naive T8-lymphocyte to become activated, proliferate, and differentiate into cytotoxic T-lymphocytes or CTLs (def) which bind to infected cells displaying those same SARS-CoV-2 viral peptides and kill those infected cells (see Fig. 3).
The dendritic cells also take up previously synthesized spike proteins (See Fig. 5, Step 7.) by endocytosis (def) which are then degraded by lysosomal enzymes into viral peptides. (See Fig. 5, Step 8.)
The endoplasmic reticulum of antigen-presenting cells (def) such as the dendritic cells also produces immunity molecules called MHC-II molecules (def) which are temporarily capped. These MHC-II molecules are then transported to the Golgi apparatus. From the Golgi apparatus the MHC-II molecules are transported to endosomes where they lose their cap and bind to viral peptides from the S-protein within the endosome. (See Fig. 5, Step 9.)
From here, the MHC-II/peptide complexes are transported to the plasma membrane of the dendritic cell where they become anchored. (See Fig. 5, Step 10.) Here, the MHC-II/peptide complexes can be recognized by naive T4-lymphocytes (def) by way of their T-cell receptors (TCRs) (def) and CD4 molecules (def) having a complementary shape. (See Fig. 6.)) This enables those T4-lymphocyte to become activated, proliferate, and differentiate into various T4 helper lymphocytes (def) that regulate immunity through the cytokines (def) they produce.
C. Johnson and Johnson-Jenssen Adenovirus DNA Vaccine for SARS-CoV-2
Unlike the mRNA vaccines for SARS-Co-V-2 mentioned above, which uses lipid nanoparticles to deliver mRNA coding for the spike or S-protein into human cells, the Johnson and Johnson-Jenssen vaccine has added a DNA gene coding for the spike protein of SARS-CoV-2 to another virus called Adenovirus 26. Adenoviruses are a group of viruses that typically cause colds or flu-like symptoms, but Adenovirus 26 has been modified so that the virus can enter human cells but cannot replicate within them or cause illness.
After injection, the adenoviruses, which are naked viruses (def) lacking an envelope, adsorb to receptors on the surface of human cells by means of protein fibers that extend from the viral capsid (def) . The viruses enter the host cell by endocytosis (def) and are placed in an endosome. Following acidification of the endosome, the endosomal membrane is lysed and the viral nucleocapsid is transported by microtubules to the nuclear membrane of the host cell where the viral particle disassembles and its DNA genome enters the nucleus through nuclear pores (see Fig. 7).
The adenovirus has been engineered so that it is unable to make copies of itself, but the gene for the SARS-CoV-2 spike protein can be read by the cell and transcribed into mRNA. The mRNA leaves the nucleus and host cell ribosomes translate the mRNA into spike proteins. From this point, the newly synthesized spike proteins stimulate humoral immunity (def) and cell-mediated immunity (def) in muscle cells and dendritic cells the same way as the corresponding spike proteins produced within cells as a result of mRNA vaccines (see above sections).
The Johnson and Johnson-Jenssen vaccine requires only a single injection, rather than the two injections needed for the Pfizer and Moderna mRNA vaccines. Also, because DNA is more stable than RNA, the vaccine can be stored in refrigerators (up to three months at 36–46°F (2–8°C). It does nor require the ultra-cold temperatures for storage needed for the mRNA vaccines).
D. Antibody-Mediated and Cell-Mediated Immune Defenses Against Viruses
Once displayed on and secreted from the cell surface, the antigenic (def) spike proteins (S-protein) cause the immune system to begin producing antibodies (def) that are able to bind to the S-protein of SARS-CoV-2, as well as activating T4-lymphocytes (def) and T8-lymphocytes (def) to fight off the infection. Thus, the vaccines induce not only humoral immunity (def) (the production of antibodies to neutralize the virus), but also cell-mediated immunity (def) (the production of cytotoxic T-lymphocytes that kill virus-infected cells).
1. B-Lymphocytes and the Production of Antibody Molecules specific to the SARS-CoV-2 Spike (S) Protein
Once a B-lymphocyte (def) possessing a B-cell receptor (BCR) (def) that is able to bind to the various peptide epitopes (def) of the S-protein on the envelope of SARS-CoV-2 (see Fig. 4), it becomes activated. it becomes activated. That B-lymphocyte then interacts with T4-helper lymphocytes (def) that have also become activated by way of SARS-CoV-2 viral peptides on MHC-II molecules (def) on dendritic cells (def) (see Fig. 5 and Fig. 6), those activated B-lymphocytes proliferate and differentiate into effector cells called plasma cells (def) that secrete antibodies that specifically bind to the S-protein of SARS-CoV-2. The binding of the antibodies to the S-protein neutralizes the virus by preventing it from binding to the ACE-2 receptors (def) on human cells. In other words, the antibodies cover up the S-protein of SARS-CoV-2 and block viral adsorption (attachment) to the host cell. If the virus can't bind to the host cell, it cannot enter the cell and replicate. (See animation.)
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2. T4-Lymphocytes and the Production of Cytokines
The primary role of T4-lymphocytes (def) is to regulate the body's immune responses through the production of regulatory molecules called cytokines (def) . Once naive T4-lymphocytes (def) are activated by dendritic cells (def), they proliferate and differentiate into T4-effector lymphocytes (def) that regulate the immune responses by way of the cytokines they produce. These cytokines collectively are involved in activating or deactivating or enhancing or suppressing virtually every aspect of the body's innate and adaptive immune responses. Some cytokines promote inflammation (def) , others suppress. Cytokines are critical to the activation and subsequent proliferation and differentiation of naive B-lymphocytes (def) , T4-lymphocytes, T8-lymphocytes (def) , and a variety of other defense cells into effector cells that fight that specific infection. However, excessive production of some of these same cytokines can in some individuals lead to the cytokine storm (def) that sometimes leads to serious, and in some cases, fatal COVID-19 infections.
3. T8-Lymphocytes and the Production of Cytotoxic T-Lymphocytes (CTLs)
One of the body's major defenses against viruses is the destruction of infected cells by cytotoxic T-lymphocytes or CTLs (def) . These CTLs are effector cells derived from naive T8-lymphocytes (def) during cell-mediated immunity. Both T8-lymphocytes and CTLs produce T-cell receptors or TCRs (def) and CD8 molecules (def) that are anchored to their surface.
a. The TCRs and CD8 molecules on the surface of naive T8-lymphocytes are designed to recognize viral peptides bound to MHC-I molecules (def) on antigen-presenting dendritic cells. This interaction enables the dendritic cell to activate that naive T8-lymphocyte and cytokines from activated T4-helper lymphocytes enable the T8-lymphocyte to proliferate and differentiate into cytotoxic T-lymphocytes (CTLs).
b. The TCRs and CD8 molecules on the surface of cytotoxic T-lymphocytes (CTLs) are designed to recognize peptide epitopes bound to MHC-I molecules on virus-infected cells. This interaction enables the CTLs to kill the virus-infected cells and stop them from producing further viruses.
During the replication of viruses within their host cell, viral proteins in the cytosol of that cell are degraded into a variety of peptide epitopes (def) by cylindrical organelles called proteasomes (def) . (See Fig. 8, Step 1.) As these various endogenous antigens (def) pass through proteasomes, proteases and peptidases chop the protein up into a series of peptides, typically 8-11 amino acids long. These peptides are then transported into the rough endoplasmic reticulum (ER) where they then bind to the grooves of newly synthesized immunity molecules called MHC-I molecules (def) . (See Fig. 8, Step 2.) The endoplasmic reticulum then transports the MHC-I 41.) which, in turn, transports the MHC-I/peptide complexes by way of an exocytic vesicle to the plasma membrane of the infected host cell where they become anchored. (See Fig. 8, Step 5.) Here, the peptide and MHC-I/peptide complexes can be recognized by cytotoxic T-lymphocytes or CTLs which bind to infected cells displaying those same SARS-CoV-2 viral peptides by way of their T-cell receptors (TCRs) and CD8 molecules (See animation.) The CTL then kills the infected cell to which it has bound by apoptosis (def) . (See animation.)
During this process, B-memory cells, T4-memory cells, and T8-memory cells develop. If the same virus again enters the body again at a later date these memory cells are usually capable of an anamnestic response that results in a heightened secondary immune response where more antibodies and CTLs are made faster, in greater amounts, and for longer periods of time. This typically prevents symptomatic reinfections with that virus.
Gary E. Kaiser, Ph.D.
Professor of Microbiology
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.
Last updated: Feb., 2021
Please send comments and inquiries to Dr.
Gary Kaiser