Exercises: 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.

What is an autoimmune disease? Name two examples and explain which immune system malfunction causes them.

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

What is an infectious agent or pathogen? Classify the main types (viruses, bacteria, fungi, protozoa) and give an example of a disease caused by each one.

What is histamine and what symptoms does it produce when it is released during an allergic reaction? State how antihistamine drugs act.

Asthma is an inflammatory disease of the airways with a frequent allergic component. Explain what happens in the bronchi during an asthma attack and why it is considered a disproportionate immune response.

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.

Excessive hygiene during childhood has been related to the increase of allergies in developed countries (the hygiene hypothesis). Explain briefly what this hypothesis consists of.

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

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.

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.

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.

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.

In multiple sclerosis, the immune system destroys the myelin that covers the neurons. Reason why it is classified as an autoimmune disease, what immune cells take part in the attack and why the symptoms depend on the area of the nervous system affected.

Transplants between identical twins barely need immunosuppression, while those performed between unrelated people do. Explain what determines that difference (identity of the HLA or MHC markers) and what the histocompatibility test performed before a transplant consists of.

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.

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 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.

A student who had never previously shown respiratory problems moves to live in Kilkenny 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 a birch wood, 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 birch pollen antigens, and reason why the friend's mast cells do not undergo degranulation.

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.

An epidemiological study compared the prevalence of allergic diseases between children raised on traditional farms (Group A), where they interact daily with livestock and soils rich in microbial endotoxins, and children raised in urban centre apartments (Group B) with strict domestic disinfection routines and scarce contact with animals. The incidence of allergic asthma in Group B was 14.2%, compared to only 2.8% in Group A.

1. a) Interpret these results drawing upon the "hygiene hypothesis": explain how early exposure to a wide microbial diversity modulates the balance between T helper lymphocyte subpopulations (Th1 versus Th2) and the activity of regulatory T lymphocytes (Treg).
2. b) A detergent company promotes a cleaner with the slogan: "Kills 99.9% of bacteria to keep your children allergy-free." Based on immunological foundations, refute the premise of this commercial slogan in a justified manner.
3. c) Does it follow from the hygiene hypothesis that water purification or the vaccination schedule should be abolished to strengthen the infant immune system? Justify your answer by distinguishing between exposure to non-pathogenic commensal environmental microorganisms and exposure to lethal virulent pathogens.

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.

In autoimmune diseases such as systemic lupus erythematosus (SLE) or Hashimoto's thyroiditis, close to 90% of diagnosed cases correspond to women. To explain this marked sex bias, the scientific community investigates hormonal factors (oestrogens tend to enhance B lymphocyte proliferation and antibody production, whereas androgens usually act as immunosuppressants) and genetic factors linked to the X chromosome (which concentrates numerous genes related to innate and adaptive immunity).

1. a) Formulate a justified hypothesis to predict whether males with Klinefelter syndrome (47,XXY karyotype) will have a risk of developing SLE more similar to that of 46,XY males or to that of 46,XX females.
2. b) From an adaptive perspective, a more vigorous humoral immune response in females confers greater resistance against bacterial and viral infections. Justify how this evolutionary advantage can translate, under certain genetic and environmental conditions, into an unfavourable cost in the form of autoimmune disease.
3. c) A primary care physician attends to a young male with symmetrical joint pain, malar rash, and positive antinuclear antibodies (ANA), but rules out the diagnosis of SLE, stating that "lupus is a disease exclusive to women." Refute this medical decision by differentiating between epidemiological probability and clinical diagnostic exclusion.

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.

Unit challenge. Imagine you are advising your school's health committee. Your mission is to assess your community's immune status against respiratory viruses and prepare a reasoned technical report.

1. Data collection: Consult the latest respiratory virus surveillance report on the website of the Health Protection Surveillance Centre (HPSC) or survey $10$ people around you about their flu vaccination to verify whether the target coverage of $75.0$ % is reached.

2. Immunological analysis: Design a comparative table distinguishing the innate versus specific immune mechanisms activated by the pathogen, classifying the type of immunity conferred by the vaccine (natural/artificial, active/passive).

3. Study of pathologies: Justify how the body would respond if the individual had a congenital immunodeficiency or experienced a hypersensitivity reaction to the inoculated antigen.

4. Final proposal: Write a one-page reasoned proposal with preventive measures to optimize herd immunity and safeguard individuals with immune disorders.

Assessment criteria:

• Accuracy in differentiating the cellular and molecular components of innate and specific immunity.

• Rigour in classifying the types of immunity and explaining immunological memory.

• Biological consistency when analyzing the proposed immune pathologies.

• Communicative clarity and scientific basis in community health proposals.