Types of immunity

Immunity can be classified as natural or artificial, and as active or passive. Explain what each of these four terms means and give an example of each possible combination.

The table in the diagram classifies types of immunity according to two criteria. Place each of the following situations in its corresponding box (1 to 4) and justify your choice: a) contracting measles; b) receiving the tetanus vaccine; c) receiving antivenom serum after a snake bite; d) a baby being breastfed.

What is a vaccine? Explain why vaccination is an example of artificial active immunity.

Suffering an infectious disease and being left protected against it is a form of immunity. State how this type of immunity is classified (natural or artificial, active or passive) and justify your answer.

Vaccines can contain attenuated microorganisms, inactivated ones, fragments of the pathogen or toxoids. Explain what all of them have in common and why it is essential that they do not cause the complete disease.

A group claims on the internet: "It is preferable for children to undergo childhood viral infections naturally to develop a stronger and more natural immunity, instead of receiving artificial vaccines loaded with foreign antigens".

1. a) Refute this argument by comparing the biological cost and the risk/benefit balance of natural active immunity versus artificial active immunity.
2. b) From a molecular and cellular point of view, justify why both an overcome infection and an effective vaccine confer long-term protection, identifying the essential similarities between both processes.
3. c) Certain wild-type pathogens such as the measles virus cause the destruction of a significant fraction of pre-existing memory lymphocytes in the patient ("immune amnesia"). Predict the consequences of this phenomenon for the child's health against other common infections and explain how vaccination prevents this effect.

The cowpox virus (cowpox) and the human smallpox virus (smallpox) present glycoproteins on their surface with antigenic epitopes of very similar three-dimensional structure, although cowpox does not trigger severe disease in humans.

1. a) Justify at a molecular and cellular level why inoculation with cowpox conferred lasting protection against smallpox, detailing the role of BCR receptors, clonal selection, and effector and memory cells.
2. b) Classify the type of immunity acquired after that initial inoculation (natural/artificial and active/passive). If serum were subsequently drawn from this individual to treat an acute smallpox patient, deduce what type of immunity the latter would receive and what key differences it would have compared to that of the donor individual.
3. c) Unlike smallpox, pathogens such as the influenza virus or SARS-CoV-2 have not been able to be eradicated with a definitive vaccination schedule. Based on the characteristics of their genomes and their biological reservoirs, predict two factors that prevent repeating the success of smallpox eradication with them.

Vaccines based on mRNA platforms contain synthetic sequences encapsulated in lipid nanoparticles that encode a viral surface antigen (such as the SARS-CoV-2 S protein).

1. a) Describe the biological sequence that takes place from the moment the lipid nanoparticle enters a dendritic or muscle cell of the vaccinated individual until the antigenic peptides are presented to T lymphocytes in a lymph node.
2. b) Refute, with cellular and molecular arguments based on the flow of genetic information in eukaryotes, two common fears: 1) that the vaccine can cause full viral infection; 2) that the mRNA can integrate into the genome and modify the recipient's DNA.
3. c) In a phase III clinical trial to evaluate the protective efficacy of the vaccine, justify the need to use a double-blind, placebo control group. Predict which specific biomarkers (humoral and cellular) must be analyzed in the volunteers' blood to confirm that the vaccine has generated both immediate protection and immunological memory.

What does an immune serum contain (obtained from a person or an animal already immunised)? Explain why its administration is considered passive immunity.

After a risk contact with the hepatitis B virus, an unvaccinated person is given gammaglobulins (concentrated antibodies). State what type of immunity they acquire and justify it.

Why does passive immunity not leave immunological memory? Reason your answer from the cells that take part, or not, in each type of immunity.

Tetanus antiserum contains pre-formed antibodies. Explain why its protection is immediate but short-lived, and why the vaccine is nonetheless also administered during the same visit.

Antitoxins (antitetanus serum, antivenom) are obtained by immunising animals, such as horses, with the toxin and then purifying their antibodies. Explain what risk administering proteins from another species has (hypersensitivity reactions, serum sickness) and how humanised monoclonal antibodies reduce that risk.

Vaccinating pregnant women against whooping cough is recommended to protect the newborn baby. Explain what mechanism of immunity transfer makes this possible, what type of immunity the baby receives and reason why repeating the vaccine in each pregnancy is recommended.

A hiker is bitten by a viper in the mountains. In the emergency room, they immediately administer heterologous hyperimmune antivenom serum (obtained from a horse), and he recovers successfully. Eight months later, the same hiker suffers a second bite from the same viper species.

1. a) Predict whether the patient will be protected against the venom in this second episode without receiving new treatment. Justify your answer by analysing the cellular and humoral mechanisms that were activated (or were not activated) following the administration of the serum in the first bite.
2. b) Describe how the plasma concentration of specific antibodies against the venom would vary over time after the first bite treated with serum, and compare it with the curve that would have been obtained if a vaccine (harmless toxoid) had been used.
3. c) Justify why the repeated administration of serum obtained from another animal species carries a serious immunological risk for the patient starting from the second dose.

What is herd immunity (or collective immunity)? Explain why it is important for a high percentage of the population to be vaccinated, even if some individuals cannot receive the vaccine.

A country eliminates measles when more than $95\ \%$ of its population is vaccinated, but the disease reappears when coverage falls. Explain, from the concept of the herd immunity threshold, why measles demands such high coverage and what happens when it drops.

An immunocompromised person cannot receive vaccines of live attenuated microorganisms. Explain why, state what types of vaccines they can indeed receive and reason how herd immunity protects them indirectly.

The herd immunity threshold ($H$) required to interrupt community transmission of a pathogen is calculated as $H = 1 - 1/R_0$, where $R_0$ is the basic reproduction number. For that threshold to be reached through vaccination, vaccination coverage ($V_c$) must satisfy the condition $V_c \times E \ge H$, where $E$ is the vaccine effectiveness on a decimal scale.

In a community, a measles outbreak is detected with $R_0 = 15$. The available vaccine has an estimated effectiveness of $95\ \%$ ($E = 0.95$).

1. a) Calculate the minimum percentage of immune individuals ($H$) that the population requires to stop the outbreak and determine the minimum vaccination coverage ($V_c$) necessary to achieve it.
2. b) Explain the immunological basis of the herd effect: why is a newborn who cannot yet receive the vaccine protected if that coverage is reached?
3. c) If in that community vaccination coverage falls to $88\ \%$, predict what will happen to the transmission of the virus. Furthermore, justify why a disease like influenza ($R_0 \approx 1.5$) tolerates much lower vaccination coverages than measles without causing uncontrolled epidemics.

A female patient with advanced kidney failure is set to undergo a transplant within three months, after which she will receive lifelong immunosuppressive treatment with drugs that inhibit the activation of helper T lymphocytes.

1. a) Justify why the administration of attenuated pathogen vaccines will be strictly contraindicated once she has undergone transplantation, predicting the clinical consequences it would have in her body.
2. b) Design a comprehensive immunological strategy to protect this patient over time, proposing three measures based on different types of immunity:

1. An active prevention measure to be carried out before the transplant surgery.

2. A community protection measure involving her household contacts and healthcare personnel.

3. An emergency rescue measure if, two years after the transplant while being immunosuppressed, she sustains a deep wound with tetanus risk.

1. c) Classify the type of immunity (natural/artificial, active/passive) operating in each of the three proposed measures and reason which one(s) will generate lasting immunological memory in the patient.

In the serological monitoring of an individual vaccinated against tetanus, it is observed that 10 years after their last dose, circulating antibodies (IgG) have fallen below the protective threshold (0.01 IU/mL). However, after administering a booster dose, they reach highly protective concentrations (> 1.0 IU/mL) in just 4 days, compared to the 12 days it took to generate them after their first vaccination in childhood.

1. a) Interpret the temporal and quantitative difference observed after the booster dose, identifying the cell populations and the selection and differentiation processes responsible.
2. b) If circulating antibodies were undetectable at 10 years, justify why it cannot be stated that the individual had completely lost their active immunity.
3. c) Predict what would happen to the response to the booster dose if the patient had developed an acquired immunodeficiency that selectively destroyed their helper T lymphocytes ($T_H$).

The yellow fever vaccine contains live attenuated viruses and protects for decades with a single dose, while the flu vaccine (inactivated viruses) must be administered every year. Reason why vaccines of live microorganisms usually generate longer-lasting immunity and why the composition of the flu vaccine changes every season.

In a preclinical trial using an animal model to stop a highly variable retrovirus, a vaccine based on the viral envelope protein isolated from a specific strain (strain A) is inoculated. The serum of the vaccinated animals successfully neutralises strain A in vitro, but it is completely ineffective against samples of the same virus obtained from the reservoir eight months later.

1. a) Interpret this failure at a genetic and molecular level: what changes have occurred in the virus and why have the neutralizing antibodies and the receptors of pre-existing lymphocytes ceased to be useful?
2. b) If you wanted to design a universal vaccine effective against all variants of that virus, propose what type of regions of the viral proteins the antigenic target should focus on and biologically justify your proposal.
3. c) As an alternative therapy, an intravenous infusion of broadly neutralizing monoclonal antibodies is administered to a patient. Classify the type of immunity provided and reasonably predict whether the patient will remain protected in the long term against future reinfections.