Specific immunity
When innate immunity is not enough to stop an invader, a defence comes into play that is much slower the first time, but aimed with pinpoint precision at that particular agent, and able to "remember" it for years. This is specific immunity, and its protagonists are the lymphocytes.
Think of the measles outbreaks the HSE warns about when uptake of the MMR vaccine in the childhood immunisation schedule drops: why does one dose protect a child for years? We come back to this at the end of the page (see "Immunological memory and clinical applications").
Antigens and lymphocytes: where they originate, where they mature
When a person receives a skin graft from another individual, their immune system attacks it and it dies within a few days, whereas a graft from their own thigh is tolerated without any problem: which molecular marks distinguish self from non-self so precisely?
What is an antigen? Give two examples of molecules or structures that can act as antigens.
What is an antigen? Give two examples of molecules or structures that can act as antigens.
State what lymphocytes are, in which organ all of them are formed and in which organs B lymphocytes and T lymphocytes mature.
State what lymphocytes are, in which organ all of them are formed and in which organs B lymphocytes and T lymphocytes mature.
Distinguish between humoral immunity and cell-mediated immunity, indicating which type of lymphocyte plays the main role in each.
Distinguish between humoral immunity and cell-mediated immunity, indicating which type of lymphocyte plays the main role in each.
Antibodies: structure and function
What is an antibody and where are antibodies found in the organism? State what type of cell produces them.
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.
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.
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…
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.
Clonal selection and receptor diversity
In a blood sample, millions of resting B lymphocytes coexist, but when tetanus toxin is introduced only the rare cell whose receptor fits it begins to proliferate massively: how does that lone cell know exactly that it must activate and multiply?
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…
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.
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…
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.
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…
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.
A laboratory wants to obtain monoclonal antibodies, that is, identical antibodies directed against a single antigenic determinant. Explain why a single clone of B…
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).
T lymphocytes and presentation by MHC
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…
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.
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…
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.
An HIV-positive patient begins treatment with a single antiretroviral agent (monotherapy with a reverse transcriptase inhibitor). During the first four months, their…
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.
- 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.
- 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…
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.
- 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.
- 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.
Immunological memory and clinical applications
A person who got over measles in childhood can, decades later, care for patients in the contagious phase without developing a single symptom: why does our immune system respond so swiftly when it comes across the same aggressor again?
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.
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.
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…
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:
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Day 7: IgM against X is detected (titer 1:64) along with trace amounts of IgG against X.
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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.
- 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.
- 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…
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:
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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.
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Patient 2 (group 0+): requires an urgent plasma transfusion (not red blood cells).
- 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.
- 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.
A patient with acute myeloid leukemia undergoes an allogeneic bone marrow transplant after receiving myeloablative chemotherapy. Two months after the transplant, they…
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.
- 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.
- 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?
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…
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:
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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%.
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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%.
- 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".
- 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.