Immunodeficiencies

Question 1

What are immunodeficiencies?

Answer 1

Conditions where parts of the immune system are missing or defective, leading to increased susceptibility to infections.

Question 2

What are the two main categories of immunodeficiencies?

Answer 2

Primary (congenital/genetic) and Secondary (acquired).

Question 3

Give examples of causes of secondary immunodeficiency.

Answer 3

Severe infections (e.g., HIV/AIDS), cancer therapies, malnutrition

Question 4

What defines primary immunodeficiencies?

Answer 4

Congenital immune defects due to genetic mutations.

Question 5

What symptoms often indicate a primary immunodeficiency?

Answer 5

Recurrent infections, especially with opportunistic or unusual pathogens.

Question 6

How are B cell immunodeficiencies characterized?

Answer 6

Low antibody levels, recurrent bacterial and fungal infections.

Question 7

What is Bruton’s X-linked agammaglobulinemia (XLA)?

Answer 7

A defect in B cell maturation due to mutation in tyrosine kinase gene, causing very low B cells and immunoglobulins

Question 8

Which gender is mostly affected by Bruton’s XLA?

Answer 8

Males (X-linked inheritance).

Question 9

What is the treatment for antibody deficiencies like XLA?

Answer 9

: Immunoglobulin (IgG) replacement therapy

Question 10

What are Hyper IgM syndromes?

Answer 10

Disorders with high IgM but defective class switching to IgG, IgA due to CD40L/CD40 defects.

Question 11

What infections are common in Hyper IgM syndrome?

Answer 11

Opportunistic infections like Pneumocystis carinii pneumonia.

Question 12

What are T cell immunodeficiencies often associated with?

Answer 12

Impaired viral and intracellular bacterial immunity.

Question 13

What is DiGeorge syndrome?

Answer 13

Failure of thymus development causing T cell deficiency.

Question 14

What is Severe Combined Immunodeficiency (SCID)?

Answer 14

Lack of functional T and B cells, often fatal without treatment.

Question 15

Name some molecular defects causing SCID.

Answer 15

Defective cytokine receptors, V(D)J recombination defects, nucleotide metabolism errors.

Question 16

What are complement defects?

Answer 16

Classical pathway defects (e.g., C1, C2, C4) → increased susceptibility to autoimmune diseases

Late component defects (e.g., C5-C9) → susceptible to Neisseria infections

C3 defect is most severe → no opsonization → severe infections

Question 17

What are examples of innate immune system defects?

Answer 17

Leukocyte Adhesion Deficiency, Chronic Granulomatous Disease, Chediak-Higashi Syndrome.

Question 18

What is Leukocyte Adhesion Deficiency?

Answer 18

Defect in integrins or selectins, impairing leukocyte migration to infection sites.

Question 19

What causes Chronic Granulomatous Disease (CGD)?

Answer 19

Failure to produce reactive oxygen species (superoxide) needed to kill pathogen

Question 20

What is Chediak-Higashi Syndrome

Answer 20

Defect in lysosomal trafficking causing impaired granule fusion in immune cells.

Question 21

What is the significance of studying primary immunodeficiencies?

Answer 21

They reveal critical functions of immune genes and pathways, often studied via human genetics and mouse models.

Question 22

What is the role of genetic linkage and microsatellite analysis in immunodeficiency?

Answer 22

Tools to link specific genetic mutations to immunodeficiency phenotypes.

Question 23

Why are immunodeficiencies often more common in males?

Answer 23

Due to many being X-linked recessive disorders.

Question 24

: What are lymphoproliferative diseases in the context of immunodeficiency?

Answer 24

Disorders with excessive lymphocyte proliferation due to defective apoptosis (e.g., Fas or Caspase defects).

Question 25

What causes X-linked lymphoproliferative disease?

Answer 25

Excessive IFN-γ and Th1 skew after EBV infection causing uncontrolled B cell proliferation.

Question 26

How does autoimmunity relate to immunodeficiency?

Answer 26

Breakdown of self-tolerance can cause autoimmune disease; defects in tolerance mechanisms may overlap with immunodeficiencies.

Question 27

What is the role of the AIRE gene?

Answer 27

Maintains central tolerance by promoting elimination of self-reactive T cells in the thymus.

Question 28

What environmental factors can trigger autoimmunity?

Answer 28

Infections (molecular mimicry), tissue damage, hormones, and superantigens

Question 29

What is molecular mimicry?

Answer 29

When immune responses to pathogens cross-react with self-tissues due to shared epitopes. M protein on bacteria is mimicked in rheumatic fever.

Question 30

Name one diagnostic method used to detect B cell immunodeficiencies.

Answer 30

ELISA or flow cytometry for Ig levels / B cell counts

Question 31

What is the main clinical symptom of Leukocyte Adhesion Deficiency (LAD)?

Answer 31

Recurrent bacterial infections and delayed umbilical cord separation

Question 32

Why do patients with SCID require bone marrow transplantation?

Answer 32

Because they lack both functional T and B cells → Bone marrow transplant provides stem cells that can reconstitute the immune system.

Question 33

List two causes of secondary immunodeficiency.

Answer 33

HIV/AIDS, chemotherapy, malnutrition, radiation therapy

Question 34

How does molecular mimicry contribute to autoimmunity?

Answer 34

Microbial epitopes resemble self-antigens, triggering an immune response against self.

Question 35

Which gene is defective in X-linked SCID?

Answer 35

. IL2RG Explanation: X-linked SCID is caused by mutations in the IL2RG gene encoding the γ-chain shared by multiple interleukin receptors, affecting T and NK cells

Question 36

What is the definition of vaccination?

Answer 36

The process of inducing protective immunity by exposing the immune system to harmless forms or parts of a pathogen (antigens) without causing disease.

Question 37

Who performed the first vaccination and for what disease?

Answer 37

Edward Jenner, smallpox, in 1796 using cowpox virus

Question 38

How does vaccination provide immunity?

Answer 38

: By mimicking infection, activating B and T cells, and generating memory cells for faster future responses.

Question 39

What are the main types of vaccines?

Answer 39

Live attenuated, inactivated, subunit, mRNA, and viral vector (Chimeric )vaccines

Question 40

: What antibody is key for mucosal immunity?

Answer 40

IgA – found in mucosal surfaces like lungs and gut.

Question 41

What is clonal selection and expansion in adaptive immunity?

Answer 41

Selection of B/T cells that recognize antigen → multiplication into effector and memory cells.

Question 42

What are the benefits of live attenuated vaccines?

Answer 42

Strong, long-lasting immunity including mucosal (IgA) response, but not suitable for immunocompromised.

Question 43

: How do mRNA vaccines like Pfizer’s COVID-19 vaccine work?

Answer 43

: They deliver mRNA for the spike protein → body makes protein → immune response develops.

Question 44

: What age do UK children receive their second MMR dose?

Answer 44

Between 3–4 years of age.

Question 45

What makes a good vaccine?

Answer 45

Safe, effective, long-lasting, induces correct immune response, and has few side effects.

Question 46

What are neutralization and opsonization?

Answer 46

Neutralization: blocking pathogen entry. Opsonization: marking pathogens for immune cell destruction.

Question 47

What is the difference between inactivated and subunit vaccines?

Answer 47

Inactivated: Whole killed pathogen. Subunit: Only specific parts like proteins or toxoids.

Question 48

What is the goal of COVID-19 vaccines?

Answer 48

Teach the body to recognize and fight the spike protein of SARS-CoV-2.

Question 49

What is the impact of vaccination on global health?

Answer 49

Eradicated smallpox, nearly eliminated polio, and reduced diseases like MMR and diphtheria.

Question 50

What does herd immunity mean?

Answer 50

When enough people are immune, reducing spread and protecting unvaccinated individuals.