Exam 4 Flashcards
What is the overall function of the immune system? How do immune cells recognize self vs. non-self?
The role of the immune system is to differentiate between home cells and outsider cells, and to defend the body from pathogenic outsiders. This system distinguishes between “self” and “other” through the recognition of surface markers on cells. MHCs (major histocompatibility complex molecules) or self markers are found on “self” cells and are made of sugars or proteins (or a combination of the two). PAMPs (pathogen-associated molecular patterns) are markers on “other” or “non-self” cells which allow the immune system to recognize certain invaders as such.
What are three different lines of defense? Which immune system (innate vs. adaptive) do they belong to?
Physical and Chemical Barriers: This includes the skin, mucous membranes, and various secretions (e.g. saliva, tears, stomach acid) that prevent pathogens from entering the body. This is a part of the innate immune system.
Innate Immune Response: This includes immune cells such as phagocytes, natural killer cells, and complement proteins that recognize and attack pathogens. This is also a part of the innate immune system.
Adaptive Immune Response: This involves the production of antibodies and the activation of T cells that specifically recognize and target pathogens. This is a part of the adaptive immune system.
The first two lines of defense (physical and chemical barriers and innate immune response) belong to the innate immune system, while the third line of defense (adaptive immune response) belongs to the adaptive immune system.
Describe two physical barriers and three chemical barriers associated with the innate immunity.
Physical Barriers -
1- Mucous membranes- Mucus can help trap microbes from entering the body
2- Skin- Dead skin cells can help remove microbes from the body
Chemical Barriers-
1- The pH in the vagina is very acidic which creates a chemical barriers like Candida
2- Lysozyme is an enzyme that eliminates microbes and is present in eyes and tears
3- Fatty acids are present in the earwax which can lower pH
In what ways is a phagocyte a tiny container of disinfectants? Briefly explain.
A phagocyte is a cell that protects the body by ingesting harmful substances that are foreign in the body. It’s a tiny container of disinfectants because it breaks down the bacteria into pus and allows it to be excreted from the body and cleaned out of the lymphatic system.
What is the complement system? Summarize three outcomes of complement activation.
The complement system is the sum of more than 30 proteins that function in complementary ways to the innate immune systems response and help trigger the adaptive immune response.
The 3 outcomes of complement activation are:
- Inflammation: The complement system has the ability to attract immune cells via chemoreceptors to the site of infection or tissue damage. As immune cells respond to the site and enact the immune response inflammation occurs. Uncontrolled inflammation can lead to tissue damage, that is why it is important that the complement system has other methods of activation.
- Opsonization: The complement system is able to enhance the process of phagocytosis by coating the surface of a pathogen with c3b proteins.
- Cytolysis: The complement system can create a membrane attack complex (MAC) that essentially punches holes in the membranes of bacterial cells, resulting swelling and eventually the bursting of the cell. This is known as cell lysis.
What does MAC stand for, and what effect does it have on bacterial cells?
MAC stands for membrane attack complex, which punctures holes in the cell membrane of the invading pathogen causing it to swell and burst.
What kinds of infections usually result in production of interferon? How does the production of IFN protect uninfected cells?
Viral infections usually result in the production of interferon. The production of interferon protects uninfected cells through binding the receptors of the neoghbors of the infected cells. preventing the cells from producing viral proteins, thus interfering with viral production, hence the name interferon.
What are the granulocytes and agranulocytes of the immune system? Describe each cell’s morphology and function.
Granulocytes are the type of white blood cells that are present in the cytoplasm, with granules in them. There are three types of granulocytes: Neutrophils: Which are made up of 3-5 lobes connected by thin strands. The most abundant type of WBCs. They are in charge of killing bacteria, fungi, and foreign debris. Then we got Eosinophils: They have a two-lobe nucleus. They’re involved in killing parasites, and cancer cells and involved in allergic responses. They stain bright pink to red. Lastly, we have Basophils: They usually have more than one lobe nucleus and would stain dark blue to purple. They’re involved in allergic responses and releasing heparin to limit the size of a forming blood clot.
A second type of WBCs is Agranulocytes which by the name it means it doesn’t have granules in the cell, and they’re of two different types. First, Lymphocytes: They have a round nucleus. Involved in fighting viruses and making antibodies. Then we have Monocytes: They’re known to be the biggest cell in size. They have a kidney bean-shaped nucleus. They clean up damaged cells. When a pathogen enters the body, they turn into macrophages, calling on other cells to help treat injury and prevent infections.
How do white blood cells squeeze through the blood vessel? What is this phenomenon called?
WBC’s can deform their cell structure, and many have multi-nucleated or multi-lobed nuclei that allow them to better fit through the endothelial cells that make up the walls of blood vessels. This is called extravasation, or diapedesis.
The process by which white blood cells squeeze through the walls of blood vessels to reach the site of infection or injury is called diapedesis or extravasation.
During diapedesis, white blood cells use a process called leukocyte adhesion and transmigration to move through the blood vessel walls. First, the white blood cells roll along the endothelial cells that line the blood vessels. Then, they adhere to the endothelial cells through a process called leukocyte adhesion, which involves the interaction between adhesion molecules on both the white blood cells and the endothelial cells. Finally, the white blood cells migrate through the endothelial cells and basement membrane and into the surrounding tissue through a process called transmigration or paracellular migration.
This process is facilitated by the formation of temporary gaps between the endothelial cells and the loosening of the basement membrane, which allows the white blood cells to squeeze through the walls of the blood vessels and reach the site of infection or injury.
What do PAMP and PRR stand for? What are their roles in phagocytosis?
PAMP stands for pathogen-associated molecular patterns (PAMPs):
These are markers on pathogens that help immune cells recognize pathogens as “non-self” and begin phagocytosis. Some examples of (PAMPS) include:
peptidoglycan, found in bacterial cell walls;
flagellin, a protein found in bacterial flagella;
lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria;
lipopeptides, molecules expressed by most bacteria; and
nucleic acids such as viral DNA or RNA.
PRR stands for pattern recognition receptors (PRRs) and they work by helping phagocytes to detect PAMPS. Some are located on the outside of phagocytes, others can be found on organelles or embedded in the membrane.
Describe the different steps of phagocytosis. What is a high neutrophil count in blood a sign of? What is pus made of?
- Injured cells secrete chemical signals
- Resident macrophages engulf pathogens and release cytokines
- Endothelial cells increase expression of adhesion molecules and receptors
- Leukocytes stick to endothelial cells and slow down
- Leukocytes squeeze through the junction between endothelial cells
- Leukocytes release chemicals to kill pathogens and engulf them
High neutrophil count in blood is a sign that the body is fighting an infection. Pus buildup is when cellular debris and bacteria at the site of infection is observed. It is a sign that the immune defense is activated against an infection.
Why is the evasion of phagocytosis a type of virulence factor? Use a specific example to explain. (HINT: we have encountered several pathogens that have different mechanisms for phagocytosis evasion. Different students can use different microbes to answer this question).
Phagocytosis is part of the immune response, during which immune cells such as macrophages engulf and digest invading pathogens. Many pathogenic microorganisms have developed strategies around phagocytosis, which is makes it a type of virulence factor.
One example of phagocytosis evasion as a virulence factor is Staphylococcus aureus. S. aureus has several mechanisms to avoid phagocytosis, including the production of cell surface proteins that prevent recognition and binding by immune cells.
What do rubor, calor, tumor and dolor mean in acute inflammation? What is the cause of each in the inflammatory process?
Rubor means redness, caused from vasodilation and increased blood flow. Calor means heat, caused by increased blood flow due to capillary widening. Tumor means swelling, caused by increased permeability of blood vessels that causes leakage of plasma proteins and fluid into the tissues. Dolor means pain, caused by the stimulation of nerve pain receptors in the tissue.
What are pyrogens? List three functions of fever.
Pyrogens are chemicals that effectively alter the “thermostat setting” of the hypothalamus, elevating body temperature and causing fever. The functions of fever include enhancing the innate immune defenses by stimulating leukocytes to kill pathogens, inhibiting the growth of many pathogens due to the rise in body temperature, and stimulating the release of iron-sequestering compounds from the liver, thereby starving out microbes that rely on iron for growth.
What are the signs and symptoms of malaria?
Symptoms: Headache, Nausea, Back pain, muscular fatigue and pain, dry cough
Signs: vomiting, fever (39-41°C [102.2-105.8°F]) , chills, sweating, spleen enlargement, faint and rapid pulse
Severe malaria:
Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities.
Severe anemia due to hemolysis (destruction of the red blood cells)
Hemoglobinuria (hemoglobin in the urine) due to hemolysis
Acute respiratory distress syndrome (ARDS), an inflammatory reaction in the lungs that inhibits oxygen exchange, which may occur even after the parasite counts have decreased in response to treatment
Abnormalities in blood coagulation
Low blood pressure caused by cardiovascular collapse
Acute kidney injury
Hyper parasitemia, where more than 5% of the red blood cells are infected by malaria parasites
Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia
What is the causative agent of malaria? Is it a prokaryote or an eukaryote?
Malaria is caused by several eukaryotic protozoan parasites in the genus Plasmodium: P. falciparum, P. knowlesi, P. malariae, P. ovale, and P. vivax.
Plasmodium belongs to the phylum apicomplexans, which are unicellular eukaryotic parasites. They have an apical complex at the end of the cell. This complex includes organelles, microtubules and vacuoles that help Plasmodium enter the host cells. Plasmodium primarily infect red blood cells. Here is an included image from the textbook showing the apical complex.
Identify the life cycle of Plasmodium in both the human host and the mosquito host. Which stages are the infectious stage and which are the diagnostic stage?
During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoitesinto the human host . Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites . After this initial replication in the liver (exo-erythrocytic schizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony ). Merozoites infect red blood cells. The ring stage trophozoites mature into schizonts, which rupture releasing merozoites. Some parasites differentiate into sexual erythrocytic stages (gametocytes). Blood stage parasites are responsible for the clinical manifestations of the disease. The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal .
The parasites’ multiplication in the mosquito is known as the sporogonic cycle. While in the mosquito’s stomach, the microgametes penetrate the macrogametes generating zygotes. The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts. The oocysts grow, rupture, and release sporozoites, which make their way to the mosquito’s salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle.
How does having the sickle cell allele affect people’s chances of survival from malaria?
People can have either one copy of the sickle cell allele, two copies, or no copies at all.:
-For those who have no copies of the allele, and produce only normal A form hemoglobin, they are at a high risk for malaria.
-For those who have two copies of the allele, they produce only the abnormal S form hemoglobin, and although they are at a low risk for malaria, they will still experience a painful disease if infected.
-Carriers of the sickle cell allele, where they have one copy of the allele, and produce both A form and S form hemoglobin, have a low risk for malaria as well, and if infected will not experience severe symptoms.
How is malaria diagnosed, prevented and treated?
Malaria is diagnosed by the clinical signs and symptoms, Plasmodium in blood smears, RDTs/EIAs that detect Plasmodium antigens or a PCR detecting parasite nucleic acids. Prevention includes mosquito nets, closing windows, avoid standing water and insect repellent to limit interaction with mosquitos. It is also recommended to take medicine before, during and after traveling to areas where malaria is present. There is also a malaria vaccine that was approved in 2021. Treatment may include drugs like chloroquine, atovaquone , artemether, and lumefantrine but some Plasmodium have been found resistant to antimalarial drugs. Since Plasmodium are protozoa, their cells are similar to human cells, which makes it hard to develop drugs that don’t cause symptoms to our body.
How are adaptive immunity and innate immunity different? List the two main differences and briefly explain.
- innate immune system is activated quickly and is non-specific, it does not have memory and responds to all pathogens the same
- adaptive immune system takes longer to develop but is more specific and at risk of redundancy – adaptive. the adaptive immune system can remember pathogens and also respond differently depending on the type of pathogen.
What are antigens and where would you find them? What are they made of? What are epitopes?
Antigens are any molecule or organism that generates an antibody response. They are found everywhere. They can be toxins, pollen, microbes, a molecule…and are made up of any of the macromolecules and/or lipids. Epitopes are short amino acid residue sequences (sometimes monosaccharide sequences) on antigens which antibodies recognize and with which they bind and mount an immune response.
What is the structure of antibodies? What are the different ways that antibodies can help combat pathogens?
Antibodies structure has 4 polypeptide chains 2 heavy chains and 2 light chains. Each chain has consistent and variable regions. Antibodies can help combat pathogens by neutralization, opsonization, and activating complement proteins. Neutralization for example, is where the antibody binds to the pathogens to prevent it from infecting or damaging host cells.
What are class I and class II MHC genes? Which cell types are they expressed, and what are their functions?
Class I and II MHC genes are involved in the immune response and plays a crucial role in presenting antigens to immune cells.
MHC (major histocompatibility complex) I present normal self-antigens molecules and abnormal (non-self) pathogens to the effector T cells that are involved in cellular immunity. They are expressed on all normal, healthy, nucleated cells which signals to the immune system that the cell is a normal “self” cell. MHC I molecules are composed of a longer α protein chain coupled with a smaller β2 microglobulin protein and only the α chain spans the cytoplasmic membrane. The α chain of the MHC I molecule folds into three separate domains: α1, α2 and α3.
MHC I molecules present antigens that is derived from intracellular pathogens such as viruses and intracellular bacteria, to cytotoxic T lymphocytes (CTLs) or CD8+ T cells. This presentation triggers an immune response which leads to the destruction of infected or abnormal cells. These molecules also help in immunosurveillance because they present self-antigens that enable the immune system to detect and eliminate cells that displays abnormal proteins, such as cancer cells.
MHC (major histocompatibility complex) II present abnormal (non-self) pathogen antigens for the initial activation of T cells. These molecules are only expressed on macrophages, dendritic cells, and B cells. MHC II molecules are composed of two protein chains (an α and a β chain) that are approximately similar in length. Both chains of the MHC II molecule possess portions that span the plasma membrane, and each chain folds into two separate domains: α1 and α2, and β1, and β2.
MHC II molecules present antigens that is derived from extracellular pathogens, such as bacteria, fungi, and parasites, to helper T lymphocytes (Th cells) or CD4+ T cells. This interaction activates the immune response and stimulates various immune cells including B cells and cytotoxic T cells, in order to eliminate the pathogens. These molecules are essential for initiating and coordinating immune responses.
Name three antigen presenting cells. What is their role in the adaptive immune system? Which classes of MHC proteins do they express and why is this important?
In adaptive immunity, antigen-presenting cells (APCs) play a crucial role. T-lymphocytes require these to operate properly. B-lymphocytes, macrophages, and dendritic cells are the three primary antigen-presenting cells.
B cells create antibodies.
B lymphocytes, also called B cells, create a type of protein called an antibody. These antibodies bind to pathogens or to foreign substances, such as toxins, to neutralize them.
Besides secreting antibodies, B cells express MHC class II and serve as antigen-presenting cells (APCs) for CD4+ T cells.
Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. They promote homeostasis by responding to internal and external changes within the body, not only as phagocytes, but also through trophic, regulatory, and repair functions.
Macrophages can process and present exogenous antigens on major histocompatibility complex (MHC) class I molecules through an alternative mechanism involving the internalization of antigens and the secretion of peptides loading MHC class I molecules at the cell surface.
Dendritic cells (DCs) represent a heterogeneous family of immune cells that link innate and adaptive immunity. The main function of these innate cells is to capture, process, and present antigens to adaptive immune cells and mediate their polarization into effector cells (1)
Dendritic cells (DCs)3 are antigen-presenting cells that play a vital role in the immune system. A major function of DCs is to capture, process, and present antigens to T cells (1). To perform this task, DCs possess MHC class II (MHC-II) proteins onto which processed antigens are loaded (2).
How do APCs activate TH cells? Draw a picture to illustrate clonal selection.
APCs interact with T cells to link innate and adaptive immune responses. By displaying bacterial and tumorigenic antigens on their surface via major histocompatibility complexes, APCs can directly influence the differentiation of T cells.
What happens when a TH cell is activated? What are clonal expansion and differentiation? How long does it take?
After activation, T cells undergo a clonal expansion and differentiation followed by a contraction phase, once the pathogen has been cleared. Cell survival and cell death are critical for controlling the numbers of naïve T cells, effector, and memory T cells.
B cell differentiation is the process by which B cells change into different types, such as plasma cells and plasma blasts. Clonal expansion is the process by which daughter cells arise from a parent cell.
After a naive lymphocyte has been activated, it takes 4 to 5 days before clonal expansion is complete and the lymphocytes have differentiated into effector cells.
During lymphocyte maturation, how does your body build immune tolerance? Do you know the consequences of failure to do so?
During lymphocyte maturation, the body builds immune tolerance by central tolerance. This process occurs in the thymus for T cells and in the bone for bone marrow B cells. The T cells undergo positive and negative selection, in the positive selection they are able to recognize self MIC molecules are allowed to mature and kill those who can’t. Negative selection T cells recognize self-antigens too strongly and are eliminated to prevent autoimmunity. If they don’t build this immune tolerance results in autoimmune diseases where the bodies immune system attacks the healthy organs and tissues.
What are the main receptors on the surfaces of T cells? What do they recognize and bind? How many different kinds of receptors are on the surface of ONE T cell (careful, this might be a trick question)?
T Cell Receptors (TCRs) are protein complexes found on the surface of T cells or T lymphocytes responsible for recognizing antigens on foreign substances. Without TCRs, the immune system would not be able to successfully identify and fight infectious disease.
T-cell receptors bind to certain antigens (proteins) found on abnormal cells, cancer cells, cells from other organisms, and cells infected with a virus or another microorganism. This interaction causes the T cells to attack these cells and helps the body fight infection, cancer, or other diseases. Also called TCR.
There are two types of T cell receptor (TCR); alpha beta and gamma delta, both of which are composed of a heterodimer and associated with invariant CD3 complexes on the cell surface.
Lymphocytes recognize a huge diversity of antigens; how do they achieve such diversity? How does VDJ recombination work?
Lymphocytes present receptors for antigen (Ag) recognition (TCR and BCR respectively) with different specificities on their surfaces. The genes that encode for these structures undergo a series of DNA recombinations, which provides them with immense phenotypic diversity.
This process, termed V(D)J recombination, chooses a pair of segments, introduces double-strand breaks adjacent to each segment, deletes (or, in selected cases, inverts) the intervening DNA, and ligates the segments together
What CD molecule is on the surface of TH cells? Describe three ways that TH cells are ‘helpers’.
CD is an abbreviation “for cluster of differentiation”. CD molecules are cell surface markers which are very useful for the identification and characterization of leukocytes and the different subpopulations of leukocytes.
Helper T cells are arguably the most important cells in adaptive immunity, as they are required for almost all adaptive immune responses. They not only help activate B cells to secrete antibodies and macrophages to destroy ingested microbes, but they also help activate cytotoxic T cells to kill infected target cells.
What CD molecule is on the surface of TC cells? How does a cytotoxic T-lymphocyte kill a virally infected cell? (Use the words “perforin”, “granzyme” and “apoptosis” in your answer.)
CD4 and CD8 co-receptors on the surface of T cells. Cytotoxic T cells (TC) express CD8, which recognizes class I MHC proteins, whereas helper T cells (TH) express CD4, which recognizes class II MHC proteins.
Cytotoxic T cells kill their targets by programming them to undergo apoptosis (Fig. 8.35). When cytotoxic T cells are mixed with target cells and rapidly brought into contact by centrifugation, they can program antigen-specific target cells to die within 5 minutes, although death may take hours to become fully evident.
Describe the B cell production and maturation process, including the locations and positive vs. negative selections.
B cell development starts in the bone marrow (BM) and continues in the spleen to final maturation. Developmental progression is guided by sequential events leading to assembly, expression, and signaling of the B cell antigen receptor (BCR).
Both B and T cells undergo positive and negative selection in the primary lymphoid organs. Positive selection requires signaling through the antigen receptor for the cell to survive. Developing B cells are positively selected when the pre-B receptor binds its ligand.
What is VDJ recombination, and how does it play a role in BCR diversity?
VDJ Recombination is a recombination of V, D, J segments into numerous combinations that makes up the variable regions of the recepeptor of lymphocytes. It plays a role in BCR diversity because through recombination, the BCR will theoretically have all the possible combination on its receptors to recognize any epitopes of antigens.
What is T cell-independent B cell activation? How long is the effect? Are memory cells produced?
Activation of B cells without the cooperation of helper T cells is referred to as T cell-independent activation and occurs when BCRs interact with T-independent antigens. T-independent antigens (e.g., polysaccharide capsules, lipopolysaccharide) have repetitive epitope units within their structure, and this repetition allows for the cross-linkage of multiple BCRs, providing the first signal for activation.
The T cell-independent response is short-lived and does not result in the production of memory B cells.
What is T cell-independent B cell activation? How long is the effect? Are memory cells produced?
Activation of B cells without the cooperation of helper T cells is referred to as T cell-independent activation and occurs when BCRs interact with T-independent antigens. T-independent antigens (e.g., polysaccharide capsules, lipopolysaccharide) have repetitive epitope units within their structure, and this repetition allows for the cross-linkage of multiple BCRs, providing the first signal for activation.
The T cell-independent response is short-lived and does not result in the production of memory B cells.
What is T cell-dependent B cell activation? How long is the effect? Are memory cells produced? What is class switch recombination?
T cell-dependent B cell activation is a process in which B cell is activated by a helper T cell in order to produce antibodies against a specific antigen. This process involves the recognition of the antigen by B cell receptors and the subsequent presentation of the antigen to T cells. The T cells then activate the B cells through the release of cytokines and other signaling molecules, leading to the proliferation and differentiation of the B cells into plasma cells that produce antibodies. The effect of this process can last for weeks to months, and memory B cells are produced to provide long-term immunity to the antigen. Class switch recombination is a mechanism by which B cells switch the class of antibody they produce without changing the specificity for the antigen.
What are primary and secondary responses? Compare the speed of reaction, the classes of antibodies produced, and the total amount of antibodies produced.
A primary immune response results in the generation of memory immune cells. A secondary immune response occurs as a result of a second exposure to an antigen. It is a much more rapid and sustained response due to the action of memory immune cells.
Primary immune response 7-10 days, Secondary immune response 3-5 days
The primary immune response is characterized by the appearance of neutralizing antibodies of the IgM class between days 4 and 7, several days before detection of IgG antibodies.
The secondary antibody response is characterized in its first few days by the production of small amounts of IgM antibody and larger amounts of IgG antibody, with some IgA and IgE.
Describe the four classes of immunity.
Innate Immunity: This is the first line of defense that our body uses to prevent infections. Innate immunity is non-specific, which means it responds the same way to all types of pathogens. The innate immune system includes physical barriers like the skin and mucous membranes, as well as cells like neutrophils and macrophages that can engulf and destroy pathogens.
Adaptive Immunity: Also known as acquired immunity, this type of immunity is specific to a particular pathogen. It involves the activation of immune cells like T-cells and B-cells that can recognize and target a specific pathogen. Once the immune system has encountered a pathogen, it creates memory cells that can quickly recognize and respond to the same pathogen in the future.
Passive Immunity: Passive immunity is acquired when antibodies produced by another organism are introduced into the body. This can occur naturally, such as when a mother passes antibodies to her baby during breastfeeding, or it can be artificially induced through the administration of antibodies, as in the case of immunoglobulin therapy.
Immunological Tolerance: Immunological tolerance refers to the ability of the immune system to recognize and tolerate the body’s own cells and tissues. Failure of this mechanism can lead to autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues. Immunological tolerance is established during embryonic development and is maintained throughout life.
What is the difference between variolation and vaccination?
The main difference between variolation and vaccination is what form of the pathogen is exposed to the person.
In variolation, a small amount of the live pathogen is exposed to the person in an attempt for the person’s adaptive immune to develop defenses without causing the person to actually get severely sick. This is an outdated method now, and is no longer used.
In vaccination, a weakened, inactivated, or dead version of the pathogen is used, or a component of the pathogen (such as the vaccine for Covid-19 which involves using a small portion of the genetic material that codes for surface protein of the virus) is used. Generally speaking, this is the standard practice in modernity in terms of creating herd immunity, and vaccines often require much testing, processing, manufacturing etc. before being introduced to the general public.
What is a live, attenuated vaccine? What are some pros and cons?
A live, attenuated vaccine uses a weakened or modified form of the pathogen to stimulate an adaptive immune response without causing illness in the patient.
Pros include:
-Strong, long lasting immunity
-mimics actual infection, meaning different strains of the pathogen may also be immunized against by just one vaccine
-live, attenuated vaccines usually require fewer doses than other forms of vaccine
Cons include:
-potential risk of the pathogen reverting back to virulent form and causing disease
-not advisable for people with compromised immune systems
-requires careful storage and transportation to maintain efficacy
What is an inactivated vaccine? What are some pros and cons?
An inactivated vaccine is a vaccine that uses the dead form of the pathogen or some inactivated version of it, meant to invoke an adaptive immune response without causing disease.
Pros:
-inactivated vaccines cannot cause disease
-safer for immunocompromised patients (compared to live attenuated vaccines)
-much more stable and easier to transport and store (compared to live attenuated vaccines)
Cons:
-long term immune response not as strong or robust as live attenuated vaccines
-duration of immunity is shorter compared to live attenuated vaccines
-booster shots will be needed to maintain immunity
What is a subunit vaccine? What are some pros and cons?
Subunit vaccines expose the patient to only the key antigens of a pathogen, rather than whole cells or viruses.
They are produced by chemically degrading a pathogen, as well as isolating its key antigens, or produce the key antigens through genetic engineering.
conjugate vaccines are a type of subunit vaccine, consisting of a proteins conjugated to a capsule polysaccharide. They developed to enhance the efficacy of the vaccines against pathogens with polysaccharide capsules, granting greatly ability got phagocytosis. Children under the age of 2 do not respond effectively, specifically to conjugate, subunit vaccines.
Because subunit vaccines have hand picked essential antigens, they have relatively low risk for causing side affects.
What are the two polio vaccines? What are the pros and cons of each, and where are they available? Why has the US stopped using the live attenuated vaccine since 2000?
The two polio vaccines are the Salk and Sabin vaccine. The pros of the Salk vaccine are that it has a longer shelf life, it lead to infection of the disease, and it cant’t cause an active it doesn’t strict conditions for storage and transportation. The cons are that it has to be given by a medical professional, it isn’t useful in controlling epidemics, it doesn’t provide intestinal immunity, doesn’t prevent reinfection and it is more difficult to manufacture and more expensive. The pros of the Sabin vaccine include prevention of reinfection, can be given orally, humoral and intestinal immunity, useful in controlling epidemics and cheaper/easier to manufacture. The cons are that it requires subzero storage temperatures, is damaged easily and it can infect cells. The United States uses the Salk vaccine, but the Sabin vaccine is useful in developing countries since it is given orally and doesn’t require medical professionals to administer it. The U.S stopped using the live attenuated vaccine because it can possibly infect people who take it and become virulent.
How long does it usually take for a new vaccine to go on market? How is vaccine safety monitored?
It usually takes at least a few years for a vaccine to be developed and go on market. Vaccine safety is monitored by loads of pre-clinical research, then clinical trials. The clinical trials examine a vaccines safety and efficacy. Following the testing, more people look at the data to determine whether it is fit to go onto market. Once it is on market, there are still institutions in place to monitor how the vaccine is “performing” within the population.
What does the vaccine mandate achieve? Who does it aim to protect?
Vaccine mandates help prevent outbreaks of contagious diseases and contribute to the overall goal of achieving herd immunity by increasing vaccination rates through making certain vaccinations a condition of employment, school attendance, or participation in certain activities. This leads to a reduction in the spread of vaccine-preventable diseases, and helps to protect those who are not immunized or who are more susceptible.
What are the signs and symptoms of measles? What are some complications that could lead to death?
The signs and symptoms can start with a high fever that begins within two weeks after the exposure. Runny nose, watery eyes and white spots inside the cheeks can develop at the initial stage. As the disease develops, a rash can start too on the face and upper neck, which can later spread out to the rest of the body. Some of the complications usually happen in immunocompromised patients, children under 5 and adults over 30. These complications include encephalitis, severe respiratory infections such as pneumonia, severe diarrhea that can lead to dehydration if not treated on time.
What is the causative agent of measles, and what kind of genome does it have?
Measles virus (MeV) is the causative agent and it is a single-stranded RNA virus. It has an envelope and glycoproteins on the surface. The RNA genome is encapsulated by the N (nucleoprotein) protein. It also includes the H protein which helps the virus bind to the host cell and the F protein that plays a role in fusion, penetration and hemolysis. There is also the M protein that promotes virion assembly and the P protein that is a RNA polymerase cofactor. Here is an image of the virus.
Do you know the viral life cycle? Do you know how proteins like H or F fit into the viral life cycle?
The virus life cycle could be divided into six steps: attachment, penetration, uncoating, gene expression and replication, assembly, and release. The viral capsid (blue) and genome (brown) are schematically drawn for the purpose of explanation. The nucleus is omitted for clarity.
What kinds of host cells does MeV infect? What tissues/organs does the infection affect? How does it cause immune amnesia?
Measles virus (MeV) primarily infects and replicates in cells of the respiratory tract, such as epithelial cells and macrophages. However, once the virus enters the bloodstream, it can spread to other tissues and organs, including the lymphatic system, skin, and CNS.
MeV causes immune amnesia by interfering with the immune system’s ability to remember previously encountered pathogens. MeV cells can selectively target and destroy memory B and T cells, which are responsible for providing long-term protection against pathogens that the body has previously encountered. This occurs through the interaction between MeV proteins and host immune receptors, leading to apoptosis or death of the memory cells. As a result, individuals who have had measles may be at increased risk of other infections, even years after they have recovered from the disease.
How is MeV transmitted? Why does the virus have a high reproduction number? When are infected individuals contagious?
MeV is transmitted through respiratory droplets produced by sneezing/coughing or direct contact with the nasal or throat secretions from an infected person. MeV is an extremely infectious disease. The virus can survive in the air for up to two hours which is why the reproduction number is high. Measles is most infection during the prodromal period and period of illness.
What is the best prevention of measles? Why is measles making a comeback? Do you know the evidence for and against the notion that there is a link between the MMR vaccine and autism?
The best prevention of measles is to get vaccinated with the MMR vaccine. Measles is making a comeback because there has been an anti vaccination movement, with some parents who believe the vaccines can give their children autism or other dangerous side effects. With less people being vaccinated it lowers the heard immunity and allows the disease to spread to more people. There is no scientific evidence I could find the proves any connection between the MMR vaccine and autism. The CDC and all other scientific research I looked at shows that the vaccines do not cause autism. Here is a link to the CDC’s page of autism and vaccines. https://www.cdc.gov/vaccinesafety/concerns/autism.htmlLinks to an external site.
How is measles diagnosed and treated?
Measles can be diagnosed from the presence of Koplik’s sport. Lab tests such as IFA, IgM titer, PCR, and viral culture are done. There is no effective treatments, but vaccination is the best way to prevent against measles.
Koplik spots are small white inflamed spots on the inside of the cheek(s) of a patient who is experiencing the early stages of measles.
What are the four types of hypersensitivities? What do A, B, C, D stand for?
The four hypersensitivity types include Types I, II, III, and IV.
A, B, C, D is a mnemonic device associated with each hypersensitivity type.
Type I is related to allergies, atopy, and anaphylaxis (A)
Type II is related to antiBodies (B)
Type III is related to the immune Complex(es). (C)
Type IV is related to Delayed responses. (D)
Describe the mechanisms of type I hypersensitivity.
Type 1 = Allergic Anaphylaxis and Atopy
Type 1 hypersensitivity reaction involve IgE antibodies against a soluble antigen, which trigger mast cell degranulation.
When a persons is exposed to an allergen, it can lead to rapid and immediate immune response which is called an allergy, this is classified as type 1 hyper sensitivity.
The 1st exposure activates a primary IgE antibody response which sensitizes an individual to type 1 hyper sensitivity on the next exposure. The first exposure activates a strong TH2 cell response. Cytokines interleukin (IL)-4 and IL-13 from the TH2 cells activate B cells specific to the same allergen, resulting in clonal proliferation, differentiation into plasma cells, and antibody-class switch from production of IgM to production of IgE. The FC regions of the IgE antibodies then bind to receptors on the surface of mast cells through out the body.
on 2nd exposure, allergens bind to IgE molecules and mast cells, crosslinking and within mast cells trigger, a reaction in which the contents of the granules in the mast cell are released into the extracellular environment. Preformed components that are released from granules include histamine, serotonin, and bradykinin degranulation.
What are the roles of IgE, mast cells, basophils, histamine and cytokines in type I hypersensitivity?
Type I hypersensitivity is also known as an immediate reaction and involves immunoglobulin E (IgE) mediated release of antibodies against the soluble antigen. This results in mast cell degranulation and release of histamine and other inflammatory mediators.
Distinguish between local (atopy) and systemic (anaphylaxis) type I hypersensitivities.
Local (atopy) type I hypersensitivity refers to localized allergic reactions. This type of reaction is commonly affecting specific tissues and organs like the skin, respiratory tract, and gastrointestinal tract. Atopic individuals usually experience symptoms in the affected area like redness, swelling, itching, or rash.
Systemic (anaphylaxis) type I hypersensitivity usually involves a severe generalized allergic reaction that affects multiple organs and tissues and can be life-threatening if it is not treated right away. Systemic individual’s experiences severe symptoms like difficulty breathing, tightness in the chest, wheezing, swelling of the face and throat, and hives. Individuals who are usually allergic to certain foods like peanuts or shellfish, medications like penicillin, latex gloves or bee stings triggers this allergic reaction. Those who are allergic to certain allergens need immediate medical attention because these are life threatening if they aren’t given epinephrine treatments or any other type of measure.
Which antibodies mediate type II hypersensitivity? Where are the antigens located?
Type II hypersensitivity is mediated by IgG and/or IgM antibodies
The antigens that these antibodies bind to are cell surface antigens or matrix-associated antigens on basement membranes.
These antibodies activate the complement system to lyse invading cells or participate in ADCC.
Describe HDN. Know who’s at risk, cause and symptoms, as well as treatment.
Hemolytic disease of the newborn (HDN) — also called erythroblastosis fetalis — is a blood disorder that occurs when the blood types of a mother and baby are incompatible
Who is affected by hemolytic disease of the newborn? Babies affected by HDN are usually in a mother’s second or higher pregnancy, after she has become sensitized with a first baby. HDN due to Rh incompatibility is about three times more likely in Caucasian babies than African-American babies.
Infants with HDN may be treated with: Feeding often and receiving extra fluids. Light therapy (phototherapy) using special blue lights to convert bilirubin into a form which is easier for the baby’s body to get rid of.
Which antibodies mediate type III hypersensitivity? Where are the antigens located?
Type III hypersensitivity is mediated by IgG and IgM antibodies. The antigens can be located in various places, including the circulation, basement membranes, and extracellular spaces of various tissues.
Know examples of one local and one systemic type III hypersensitivities.
systemic type III: serum sickness caused by immune complexes involving no self proteins are deposited in various body sites resulting in a generalized systemic inflammatory response.
Local type III: Arthus Reaction caused by soluble antigens that bind with IgG in a ration that results in the accumulation of antigen-antibody aggregates (Immune complexes).
Why is type IV called ‘delayed response’? Which branch of adaptive immunity is involved?
The first three types are considered immediate hypersensitivity reactions because they occur within 24 hours. The fourth type is considered a delayed hypersensitivity reaction because it usually occurs more than 12 hours after exposure to the allergen, with a maximal reaction time between 48 and 72 hours.
Cell mediated
Know a local and a systemic example of type IV hypersensitivities
systemic examples include contact dermatitis, poison ivy, tuberculin skin test, and certain drug reactions, such as allopurinol. Treatment options for Type IV hypersensitivity may include medications like corticosteroids and avoiding exposure to the triggering antigen.
Autoimmune diseases are the development of hypersensitivity to your own cells. What are some possible causes?
The exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or viruses) or drugs may trigger changes that confuse the immune system. This may happen more often in people who have genes that make them more prone to autoimmune disorders.
What is celiac disease? Which organ(s) does it mainly affect? What is a gluten-free diet and what does it achieve?
An immune reaction to eating gluten, a protein found in wheat, barley, and rye.
Over time, the immune reaction to eating gluten creates inflammation that damages the small intestine’s lining, leading to medical complications. It also prevents absorption of some nutrients (malabsorption).
The classic symptom is diarrhea. Other symptoms include bloating, gas, fatigue, low blood count (anemia), and osteoporosis. Many people have no symptoms.
The mainstay of treatment is a strict gluten-free diet that can help manage symptoms and promote intestinal healing.
What are Graves and Hashimoto diseases? Which organ(s) does it mainly affect?
Both Graves’ disease and Hashimoto’s disease are autoimmune disorders that result when antibodies from your immune system begin to attack the thyroid. The differing antibodies have opposite effects on the gland, however. While Hashimoto’s causes the thyroid to become underactive, Graves’ makes it overactive.
How do you think Graves and Hashimoto diseases are treated? Why do you think they might be hard to treat?
Medical management of Graves’ and Hashimoto’s is paramount, and in some cases, all that is needed. Expert surgery remains the best and most reliable treatment option to definitively cure both of these thyroid conditions.
What is type I diabetes? Which organ(s) does it mainly affect? How does it affect the patient?
What is type 1 diabetes? Type 1 diabetes is a serious condition where your blood glucose (sugar) level is too high because your body can’t make a hormone called insulin. This happens because your body attacks the cells in your pancreas that make the insulin, meaning you can’t produce any at all.
What is Addison disease? Which organ(s) does it mainly affect? How does it affect the patient?
Addison’s disease is caused by damage to the adrenal glands. The adrenal glands sit just above the kidneys. As part of the endocrine system, they make hormones that affect almost every organ and tissue in the body. Damage to these glands results in too little of the hormone cortisol and, often, the hormone aldosterone.
What is multiple sclerosis? What is the cause of MS?
MS is a condition that can affect the brain and the spinal cord, causing a wide range of potential symptoms, some of them mild and others can cause serious disability. Though there is no specific cause, it is said that in MS the immune system attacks the protective coat of the nerves called the myelin sheath. This damaging can mean in a slowing or disruption of the messages traveling along those nerves. There’s other factors like environmental or genetics or a combination that might be involved.
What is myasthenia gravis and what causes it?
Antibodies—Myasthenia gravis is caused by an error in how nerve signals are transmitted to muscles. It occurs when communication between the nerve and muscle is interrupted at the neuromuscular junction—the place where nerve cells connect with the muscles they control.
What are psoriasis and rheumatoid arthritis?
Psoriatic arthritis is a type of arthritis linked with psoriasis, a chronic skin and nail disease. Psoriasis causes red, scaly rashes and thick, pitted fingernails. Psoriatic arthritis is similar to rheumatoid arthritis (RA) in symptoms and joint swelling (inflammation). But it tends to affect fewer joints than RA.
What is SLE / Lupus? What are some diagnostic tests?
Antinuclear Antibody Tests
An antinuclear antibody (ANA) blood test measures the presence of antibodies that are directed against the body’s cells, a sign of systemic lupus erythematosus. ANA is present in nearly everyone with active lupus.
Rejection of the transplanted organ is actually a sign of a healthy immune system. Which branch of adaptive immunity is mainly involved?
Hyperacute rejection is usually caused by specific antibodies against the graft and occurs within minutes or hours after grafting. Acute rejection occurs days or weeks after transplantation and can be caused by specific lymphocytes in the recipient that recognize human leukocyte antigens in the tissue or organ grafted.
Describe the 4 classes of grafts.
The four types of grafts are:
(i) allograft Listen to pronunciation. (A-loh-graft) The transplant of an organ, tissue, or cells from one individual to another individual of the same species who is not an identical twin.
(ii) autograft A patient’s own tissue - an autograft - can often be used for a surgical reconstruction procedure. Autograft tissue is the safest and fastest-healing tissue that can be used. However, harvesting autograft tissue creates a second surgical site from which the patient must recover.
(iii) xenograft The transplant of an organ, tissue, or cells to an individual of another species.
(iv) isograft. Skin autograft (isograft) is a graft transferred from a donor to a recipient site in the same individual. Skin allograft (homograft) is a graft transplanted between genetically disparate individuals of the same species. Skin xenografts (heterografts) are grafts transplanted between individuals of different species.
What is the main difference between primary and secondary immunodeficiency? What are the causes of primary immunodeficiency? What are the causes of secondary immunodeficiency?
Primary immunodeficiencies are a group of more than 400 rare, chronic disorders that impact the ability of the body to fight infection. Onset can occur in childhood or early adulthood. Secondary immunodeficiencies, by contrast, occur after an additional immune stress that the body experiences.
Many primary immunodeficiency disorders are inherited — passed down from one or both parents.
B cell (antibody) deficiencies.
T cell deficiencies.
Combination B and T cell deficiencies.
Defective phagocytes.
Complement deficiencies.
Unknown (idiopathic)
Secondary immunodeficiency (SID) occurs when the immune system is weakened by another treatment or illness. What causes secondary immunodeficiency? There are many potential causes of SID but the most common examples are blood or bone marrow disorders, drugs (medicines) and treatment for cancer.
