Disorders of the immune system

What is an allergy? Give two examples of common allergens and explain what occurs in the body of an allergic person when they come into contact with them.

The diagram represents the activation of a mast cell in a connective tissue at the molecular level.

1. a) Deduce what particles A and molecules B represent. Justify which isotype the membrane-bound immunoglobulins belong to and which of their regions (Fab or Fc) binds to the mast cell receptor and which to particle A.
2. b) A laboratory tests two drugs to prevent allergic crises: Drug 1 (a monoclonal antibody that specifically blocks the free Fc portion of these immunoglobulins before they contact the mast cell) and Drug 2 (a competitive antagonist of the receptors for molecule B). Reasonably predict which of the two drugs would be completely useless if administered to a patient after mast cell degranulation has already begun.
3. c) An unsensitized person suffers a wasp sting for the first time in their life. A companion insists on injecting them with emergency adrenaline, claiming that "the venom will cause immediate anaphylactic shock." Based on the immune mechanism in the diagram, refute this claim and justify what critical vascular alteration causes death in true anaphylactic shock if it is not reversed in time.

A student who had never previously shown respiratory problems moves to live in Jaén in the month of April. During that first spring, he does not experience any discomfort. However, in the middle of the following spring, after a walk through an olive grove, he develops severe allergic rhinitis with paroxysmal sneezing, itchy eyes, and rhinorrhoea in less than ten minutes.

1. a) The student claims that "his immune system completely ignored the pollen the first year and only learned to attack it in the second year." Refute this statement by deducing which cellular and molecular processes occurred asymptomatically during the first spring (sensitisation stage).
2. b) Justify at a molecular and cellular level why in the second year the symptomatic response takes only a few minutes to trigger, comparing the kinetics of this reaction with that of a classic primary adaptive immune response.
3. c) If we perform a serological test on this student and a non-atopic friend of his who was walking with him, predict what quantitative and qualitative differences will be observed in total and specific plasma IgE levels for olive pollen antigens, and reason why the friend's mast cells do not undergo degranulation.

In type 1 diabetes, the immune system destroys the insulin-producing beta cells of the pancreas. Explain why it is considered an autoimmune disease and account for why its treatment consists of administering insulin.

In systemic lupus erythematosus, autoantibodies are produced against components of the nucleus of one's own cells. Explain what autoantibodies are, why this disease can affect several organs at once and why its diagnosis includes the search for antinuclear antibodies in the blood.

A 50-year-old female patient with severe rheumatoid arthritis does not experience improvement with anti-inflammatory drugs. Her specialist decides to prescribe biological treatment with infliximab, a monoclonal antibody that specifically blocks tumour necrosis factor alpha (TNF-α). Before starting treatment, the hospital protocol mandatorily requires a tuberculin skin test (Mantoux) and a chest X-ray.

1. a) Justify the biological mechanism by which the neutralisation of TNF-α succeeds in halting chronic inflammation and articular cartilage destruction in this autoimmune pathology.
2. b) Reason why it is essential to rule out a latent Mycobacterium tuberculosis infection before administering infliximab: explain the normal defensive role of TNF-α in the formation and maintenance of the granulomas that confine this intracellular microorganism, and predict what complication would occur if the drug is administered to a person with silent tuberculous infection.
3. c) The patient trusts that this biological treatment will "repair her immune system and permanently cure rheumatoid arthritis." Refute this expectation by explaining why the monoclonal antibody acts as a palliative/anti-inflammatory therapy and does not correct the loss of self-tolerance that caused the disease.

What is an immunodeficiency? Distinguish between primary and acquired immunodeficiency, and give an example of each type.

HIV causes AIDS. Explain which cell of the immune system it infects, why the patient's defences weaken over time, and what opportunistic infections are that appear in the final stage.

An eight-month-old male infant is diagnosed with X-linked agammaglobulinemia (Bruton's disease), a congenital immunodeficiency due to a block in the maturation of B lymphocytes in the bone marrow.

1. a) The clinical history reveals that the baby was completely healthy during his first five months of life, but starting from the sixth month he began to suffer from recurrent pneumonia and otitis media caused by extracellular pyogenic bacteria (Streptococcus pneumoniae). Justify the apparent protection during the first months and reason why the lack of antibodies makes him specifically vulnerable to encapsulated extracellular bacteria (mention the role of opsonisation).
2. b) Paradoxically, the infant overcomes common viral infections, such as chickenpox or measles, without major complications. Interpret this fact based on the components of the immune system that remain intact in this patient.
3. c) The paediatrician advises against administering attenuated bacterial vaccines to him and instead prescribes periodic intravenous injections of purified human immunoglobulins from healthy donors. Justify the type of immunity (active or passive; natural or artificial) conferred by this replacement therapy and explain why it does not generate immunological memory in the child.

What is contagion? Describe two routes of transmission of pathogens (respiratory, digestive, by contact, by vectors or sexual and blood-borne) and one effective prevention measure for each.

Put the stages of an infectious disease in order (convalescence period, incubation, acute phase, decline) and briefly describe what occurs in each.

Antibiotics cure bacterial infections but not viral ones. Explain why (viruses use the machinery of our cells and lack targets such as the cell wall), reason why the abuse of antibiotics selects resistant bacteria and explain what antibiotic resistance means as a public health problem.

Coeliac disease is an immune reaction to gluten that damages the mucosa of the small intestine. Explain why it is not considered a classic food allergy (T lymphocytes and autoantibodies are involved, with an autoimmune component) and what its only effective treatment is today.

A woman with a severe allergy to wasp venom begins specific immunotherapy treatment (increasing subcutaneous doses of venom administered periodically over 3 years). Throughout the therapy, her tests show a notable increase in regulatory T lymphocytes (Treg) producing IL-10 and TGF-β, a significant increase in specific IgG4 antibodies, and a slight decrease in the concentration of specific IgE. After two years of treatment, she suffers an accidental sting in the countryside and shows no anaphylactic symptoms.

1. a) Interpret the mechanism by which induced Treg lymphocytes suppress the allergic response, indicating on which lymphocyte populations (Th2) and effector cells (mast cells and basophils) they exert their immunomodulatory action.
2. b) Reason how IgG4 antibodies act as "blocking antibodies": why does their binding to wasp venom prevent massive mast cell degranulation even though the patient still retains IgE molecules bound in her body?
3. c) If, due to medical error, a high dose of allergen were administered to the patient from the first day of treatment instead of following a progressive scaling of tiny concentrations over months, predict what immediate immunological response would be triggered and justify why the gradual dose increase is indispensable for inducing tolerance.

A 48-year-old patient receives a kidney transplant from an unrelated deceased donor. To minimize the risk of graft failure, the medical team evaluates immunological compatibility and prescribes an immunosuppressive regimen.

1. a) Explain which membrane protein complex determines compatibility between donor and recipient, and describe the cellular immune mechanism (helper and cytotoxic T lymphocytes) that would lead to graft destruction if immunosuppressants were not administered.
2. b) Eight weeks after the transplant, with the kidney functioning normally under intensive immunosuppressive treatment, the patient is admitted with high fever due to a cytomegalovirus (CMV) reactivation and a respiratory infection caused by an opportunistic fungus. Justify why immunosuppressants preferentially increase vulnerability to viruses, intracellular pathogens, and fungi, rather than to most common extracellular bacteria.
3. c) Frame the therapeutic dilemma faced by the medical team: reason what would happen to the graft if immunosuppressive treatment is discontinued to fight the infection, and what would happen to the patient's life if the dose is increased to protect the kidney.