Exercises: Specific immunity

What is an antigen? Give two examples of molecules or structures that can act as antigens.

Distinguish between humoral immunity and cell-mediated immunity, indicating which type of lymphocyte plays the main role in each.

Observe the diagram and state which of the two cells (A or B) is a B lymphocyte and which is a T lymphocyte. Explain what each is doing and to which type of specific immunity its action corresponds.

What is an antibody and where are antibodies found in the organism? State what type of cell produces them.

Distinguish between antigen and antibody, and explain what it means that the binding between them is specific, comparing it to a key and its lock.

What are immunological memory cells? Explain why, after suffering certain diseases such as measles, one does not usually fall ill with the same disease again.

State what lymphocytes are, in which organ all of them are formed and in which organs B lymphocytes and T lymphocytes mature.

Antibodies do not destroy pathogens directly: they mark them and neutralise them. Explain two ways in which an antibody helps to eliminate a pathogen (neutralisation, opsonisation, agglutination or complement activation).

Describe the basic structure of an antibody (immunoglobulin): how many chains form it, what shape it has, and which part of the molecule recognises and binds to the antigen.

Helper T lymphocytes (CD4) coordinate the specific immune response. Explain what functions they perform and what happens in the body when HIV progressively destroys them.

Explain what cytotoxic T lymphocytes (CD8) do and why they are particularly important against virus-infected cells and tumour cells.

When a B lymphocyte encounters the antigen it recognises, it proliferates forming a clone. Explain what clonal selection consists of and what two types of cells are generated from that activated lymphocyte, stating the function of each one.

Each lymphocyte has receptors for a single antigen, but the organism can respond to millions of different antigens. Explain how that enormous diversity of receptors is generated during the maturation of lymphocytes (rearrangement of the immunoglobulin genes) and why it is not necessary to have a different complete gene for each antibody.

MHC class I molecules present antigens produced inside the cell (for example, from a virus), and class II molecules present antigens that have been phagocytosed. State which type of T lymphocyte recognises each class of MHC and reason why this distribution makes biological sense.

Plasma cells are veritable antibody factories: they can secrete thousands of molecules per second. Relate this function to their appearance under the microscope (a very developed rough endoplasmic reticulum and a prominent Golgi apparatus) and reason why they live for a short time but leave memory cells behind.

A laboratory wants to obtain monoclonal antibodies, that is, identical antibodies directed against a single antigenic determinant. Explain why a single clone of B lymphocytes produces monoclonal antibodies and cite two applications of these antibodies in medicine (diagnosis or treatment).

In a clinical trial, the serum concentration of antibodies (IgM and IgG) is quantified in a volunteer after injecting them with antigen X on day 0 and a mixture of antigens X and Y on day 28. The following results are obtained:

• Day 7: IgM against X is detected (titer 1:64) along with trace amounts of IgG against X.

• Day 35 (7 days after the 2nd injection): the titers against X are IgM (1:32) and IgG (1:2048), whereas against Y only IgM (1:64) is detected.

1. a) Interpret these results, justifying what type of immune response (primary or secondary) has occurred against each antigen after day 28 and which cells are responsible for the dramatic increase in anti-X IgG.
2. b) Predict what would happen to the IgG and IgM titers against Y if a new dose of antigen Y is administered on day 56. Justify your answer in terms of immunological memory and explain its implication in the design of vaccination schedules with booster doses.

The laboratory of a field hospital has red blood cell concentrates and plasma units from donors of groups A, B, AB, and 0 (all Rh+). Two polytrauma patients arrive requiring urgent support:

• Patient 1 (group AB+): requires an urgent transfusion of red blood cell concentrate, but the blood bank has run out of group AB+ red blood cells.

• Patient 2 (group 0+): requires an urgent plasma transfusion (not red blood cells).

1. a) Justify with reasoning which type of red blood cells (A, B, or 0) you could safely transfuse to Patient 1 and what immunological mechanisms would cause a hemolytic shock if an incompatibility occurred.
2. b) A novice technician proposes transfusing group 0 plasma to Patient 2, stating that "group 0 is the universal donor and never causes problems." Refute their statement by analyzing what the plasma of a group 0 donor contains, and deduce which type of plasma (A, B, AB, or 0) would be suitable for Patient 2 and whether, in this specific case, the technician's proposal is acceptable.

In an in vitro experiment, mature B lymphocytes and helper T lymphocytes (CD4+) from a mouse previously immunized against an extracellular bacterial toxin are incubated separately. The purified toxin in its native conformation is added to both cell-free cultures.

1. a) After 48 hours, it is observed that B lymphocytes proliferate and secrete specific antibodies, whereas CD4+ T lymphocytes remain completely inactive. Justify this result based on the structural nature of BCR and TCR receptors and the activation requirements of each cell lineage.
2. b) The T lymphocyte assay is repeated by adding macrophages from the same mouse that have previously phagocytosed and processed the toxin. Predict what will happen in this case and what would happen if the added macrophages came from a mouse strain with incompatible MHC alleles. Justify your answer considering the phenomenon of MHC restriction.

A patient with acute myeloid leukemia undergoes an allogeneic bone marrow transplant after receiving myeloablative chemotherapy. Two months after the transplant, they present with a diffuse skin rash, severe diarrhea, and hepatic jaundice, but biopsies demonstrate that the engrafted hematopoietic stem cells have not been destroyed.

1. a) Diagnose the immunological complication the patient is suffering from, clearly distinguishing whether the effector cells of the tissue damage originate from the donor or the recipient, and justifying why this pathology is characteristic of bone marrow transplantation and does not usually appear in solid organ transplants such as kidney or heart.
2. b) If the patient was properly vaccinated against tetanus prior to the transplant and the donor never received that vaccine, justify whether the recipient remains protected in the long term against tetanus toxin or if they need to be vaccinated again. Which immune cells justify your answer?

An HIV-positive patient begins treatment with a single antiretroviral agent (monotherapy with a reverse transcriptase inhibitor). During the first four months, their plasma viral load drops to undetectable levels. However, by the sixth month, the viral load experiences a significant rebound despite maintaining strict adherence to the medication.

1. a) Interpret the biological cause of this virological rebound considering the mutation rate of reverse transcriptase, and justify why combined antiretroviral therapy (cART, with at least three drugs targeting different targets) effectively prevents this phenomenon.
2. b) A new experimental drug manages to eliminate 100% of free virions in blood and actively infected cells. However, if the patient stops therapy, the virus reappears within a few weeks. Explain at the cellular and molecular level where the virus "hides" during treatment and why the immune system does not detect or destroy these reservoir cells.

During the design of a vaccine against a novel pathogenic virus, two platforms are compared: one based on the purified viral spike protein administered with a classical adjuvant (subunit vaccine) and another based on lipid nanoparticles containing mRNA that encodes this viral protein.

1. a) Deduce the intracellular processing and antigen presentation pathway that the protein generated after injecting the mRNA vaccine will follow in a dendritic cell, and explain why this platform effectively induces cytotoxic T cells (CD8+) as well as helper T cells (CD4+) and B cells, unlike the purified protein vaccine.
2. b) From a biosafety perspective, justify why the mRNA vaccine does not present the risk of reversion to virulence seen in traditional live attenuated virus vaccines, nor the risk of gene integration into the host DNA.

The following table shows the clinical and analytical data of two 45-year-old patients, with no prior medical conditions, on the seventh day from the onset of symptoms of an acute respiratory viral infection:

• Patient A: Nasopharyngeal viral load: very low; Serum IL-6: 12 pg/mL (normal value: < 7 pg/mL); C-reactive protein: 8 mg/L (normal value: < 5 mg/L); Baseline O2 saturation: 97%.

• Patient B: Nasopharyngeal viral load: very low; Serum IL-6: 185 pg/mL (normal value: < 7 pg/mL); C-reactive protein: 140 mg/L (normal value: < 5 mg/L); Baseline O2 saturation: 86%.

1. a) Interpret the apparent paradox in Patient B: how is it explained that, despite already having a very low viral load, they present a much more severe clinical picture of respiratory failure than Patient A? Justify the underlying immunological phenomenon and the concept of a "cytokine storm".
2. b) In a clinical case conference, one physician proposes administering a massive dose of antivirals to Patient B, while another suggests administering IL-6 receptor-blocking monoclonal antibodies alongside glucocorticoids (immunosuppressants). Reason which of the two therapeutic strategies is biologically appropriate at this stage for Patient B and what the consequence of applying the discarded option would be.

The cells of certain malignant tumors express very high concentrations of the ligand PD-L1 on their surface, which interacts specifically with the inhibitory receptor PD-1 expressed on the membrane of cytotoxic T lymphocytes (CD8+) infiltrating the tumor stroma.

1. a) Model or schematically describe the molecular interaction between the tumor cell and the cytotoxic T lymphocyte (considering both the tumor peptide-MHC I complex with the TCR and the PD-L1 axis with PD-1) and deduce why this mechanism allows the tumor to evade the adaptive immune response despite expressing mutational neoantigens on its surface.
2. b) In clinical trials, monoclonal antibodies are used that bind to the PD-1 receptor and block its interaction with PD-L1. Predict the expected antitumor response in patients following treatment and reason why between 15% and 25% of them develop autoimmune adverse effects such as thyroiditis, colitis, or vitiligo.