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Questions and Answers
What is the main reason for the isolation of patients with myeloid lineage immunodeficiencies?
What is the main reason for the isolation of patients with myeloid lineage immunodeficiencies?
Which of the following describes a consequence of defects in the myeloid cell lineage?
Which of the following describes a consequence of defects in the myeloid cell lineage?
What is the term for a significant reduction in peripheral blood neutrophils below 1500/mm³?
What is the term for a significant reduction in peripheral blood neutrophils below 1500/mm³?
What genetic factor is commonly associated with severe congenital neutropenia (SCN)?
What genetic factor is commonly associated with severe congenital neutropenia (SCN)?
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Which of the following stages is NOT identified as potentially faulty in phagocytic processes?
Which of the following stages is NOT identified as potentially faulty in phagocytic processes?
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What is the primary consequence of Severe Combined Immunodeficiency (SCID) in infants?
What is the primary consequence of Severe Combined Immunodeficiency (SCID) in infants?
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Which type of infections are SCID infants most susceptible to?
Which type of infections are SCID infants most susceptible to?
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Why are B-cell defects not apparent in the first few months of life in SCID infants?
Why are B-cell defects not apparent in the first few months of life in SCID infants?
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What complications can arise from live attenuated vaccines in SCID patients?
What complications can arise from live attenuated vaccines in SCID patients?
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What is a suggested method to prolong the life of SCID patients?
What is a suggested method to prolong the life of SCID patients?
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What is the main difference between primary and secondary immunodeficiencies?
What is the main difference between primary and secondary immunodeficiencies?
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Which of the following conditions is characterized by the immune system attacking the host's own cells?
Which of the following conditions is characterized by the immune system attacking the host's own cells?
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Which type of primary immunodeficiency disorder involves defects in both B-cells and T-cells?
Which type of primary immunodeficiency disorder involves defects in both B-cells and T-cells?
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What results from the immune system failing to protect the host from disease-causing agents?
What results from the immune system failing to protect the host from disease-causing agents?
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Which of the following is true about primary immunodeficiencies?
Which of the following is true about primary immunodeficiencies?
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What is the primary purpose of administering pooled human gamma globulin in immunodeficiencies?
What is the primary purpose of administering pooled human gamma globulin in immunodeficiencies?
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Which treatment strategy involves the replacement of missing or defective genes?
Which treatment strategy involves the replacement of missing or defective genes?
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What must happen to CD34+ progenitor cells before they are reinfused into a patient during bone marrow transplantation?
What must happen to CD34+ progenitor cells before they are reinfused into a patient during bone marrow transplantation?
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What is the minimum serum immunoglobulin level recommended to prevent most common infections in primary immunodeficiencies?
What is the minimum serum immunoglobulin level recommended to prevent most common infections in primary immunodeficiencies?
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What is the role of recombinant adenosine deaminase in the treatment of ADA-SCID patients?
What is the role of recombinant adenosine deaminase in the treatment of ADA-SCID patients?
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Which of the following is NOT a treatment option for immunodeficiencies?
Which of the following is NOT a treatment option for immunodeficiencies?
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What type of cells are primarily harvested for bone marrow transplantation?
What type of cells are primarily harvested for bone marrow transplantation?
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In the context of maintaining immunity, what is the significance of gene replacement therapies?
In the context of maintaining immunity, what is the significance of gene replacement therapies?
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What is the most common secondary immunodeficiency?
What is the most common secondary immunodeficiency?
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Which type of cell is primarily affected in B-cell immunodeficiency disorders?
Which type of cell is primarily affected in B-cell immunodeficiency disorders?
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What is a common consequence of defective phagocytic function?
What is a common consequence of defective phagocytic function?
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Which condition is characterized by extremely low IgG levels and absence of other immunoglobulin classes?
Which condition is characterized by extremely low IgG levels and absence of other immunoglobulin classes?
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The BTK gene is crucial for the development of which type of immune cells?
The BTK gene is crucial for the development of which type of immune cells?
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Which of the following describes how X-linked agammaglobulinemia (XLA) is inherited?
Which of the following describes how X-linked agammaglobulinemia (XLA) is inherited?
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During which stage of development do B cells become pre-B cells?
During which stage of development do B cells become pre-B cells?
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What type of immune response is generally unaffected in patients with B-cell immunodeficiency?
What type of immune response is generally unaffected in patients with B-cell immunodeficiency?
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What is a likely outcome for a child with XLA in the first few months of life?
What is a likely outcome for a child with XLA in the first few months of life?
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What is the primary cellular defect in reticular dysgenesis?
What is the primary cellular defect in reticular dysgenesis?
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Which infections are most commonly associated with B-cell immunodeficiency disorders?
Which infections are most commonly associated with B-cell immunodeficiency disorders?
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In which population is X-linked agammaglobulinemia most likely to occur?
In which population is X-linked agammaglobulinemia most likely to occur?
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What is the primary consequence of having selective IgA deficiency?
What is the primary consequence of having selective IgA deficiency?
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What impact does the defect in the BTK gene have on B-cell development in XLA patients?
What impact does the defect in the BTK gene have on B-cell development in XLA patients?
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Which infections are commonly associated with X-linked agammaglobulinemia (XLA)?
Which infections are commonly associated with X-linked agammaglobulinemia (XLA)?
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What is the primary effect of a T-cell deficiency on the immune system?
What is the primary effect of a T-cell deficiency on the immune system?
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What is the impact of DiGeorge syndrome on T-cell function?
What is the impact of DiGeorge syndrome on T-cell function?
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What is the consequence of combined T and B-cell immunodeficiency disorders in infants?
What is the consequence of combined T and B-cell immunodeficiency disorders in infants?
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In Severe Combined Immunodeficiency (SCID), what is a notable feature observed in T cells?
In Severe Combined Immunodeficiency (SCID), what is a notable feature observed in T cells?
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Which genetic defect is associated with the failure of functional immunoglobulin synthesis in SCID?
Which genetic defect is associated with the failure of functional immunoglobulin synthesis in SCID?
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What type of infections are individuals with T-cell deficiencies particularly susceptible to?
What type of infections are individuals with T-cell deficiencies particularly susceptible to?
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What role do CD4 (T helper) cells play in the immune system?
What role do CD4 (T helper) cells play in the immune system?
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What is one of the key features of T-cell immunodeficiency disorders?
What is one of the key features of T-cell immunodeficiency disorders?
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What leads to decreased antibody levels in individuals with T-cell defects?
What leads to decreased antibody levels in individuals with T-cell defects?
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What is a significant characteristic of patients with XLA?
What is a significant characteristic of patients with XLA?
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How does the absence of a thymus affect T-cell populations?
How does the absence of a thymus affect T-cell populations?
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What type of immune responses are particularly affected in patients with immune disorders involving the thymus?
What type of immune responses are particularly affected in patients with immune disorders involving the thymus?
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What is the prognosis for infants with untreated combined T and B-cell immunodeficiencies?
What is the prognosis for infants with untreated combined T and B-cell immunodeficiencies?
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Study Notes
Immunology II - BMS44210A
- Course offered at Abu Dhabi University
- Instructor: Dr. Afsheen Raza
- Email: [email protected]
- Fall Semester 2024-2025
Immunodeficiencies and Autoimmunity (CLO4)
- Learning Objectives:
- Primary immunodeficiencies of lymphoid lineage
- B-cell, T-cell, and combined T and B-cell immunodeficiency disorders
- Primary immunodeficiencies of the myeloid lineage
- Testing for primary immunodeficiencies
- Treatment of primary immunodeficiencies
Immunodeficiencies and Autoimmunity
- Immune system failure can have unintended consequences
- Autoimmunity occurs when the immune system misidentifies self and attacks host cells/tissues.
- Immunodeficiency results from the immune system failing to protect the host from pathogens or malignancies.
Immunodeficiencies
- Primary immunodeficiency is a genetic or developmental defect within the immune system, present at birth.
- Symptoms might not manifest until later in life.
- Secondary immunodeficiency (acquired) is the loss of immune function due to exposure to various agents.
- Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus 1 (HIV-1) infection.
Primary Immunodeficiencies
- Can affect either adaptive or innate immune functions.
- Adaptive immunodeficiencies involve components of adaptive immunity such as T and B cells.
- Innate immunodeficiencies impair components of the innate system such as phagocytes or complements.
- Most immunodeficiency-causing defects affect lymphoid and myeloid cells.
- Lymphoid disorders impact T, B, or both cells.
- Myeloid disorders affect cells with phagocytic function.
Recall - Lymphoid or Myeloid Lineages
- Visualizes the development of lymphoid and myeloid lineages.
- Lymphoid progenitor cells give rise to all lymphoid cells.
- Myeloid progenitor cells give rise to all myeloid cells.
- Dendritic cells can originate from either lineage.
Primary Immunodeficiencies
- Most are inherited
- Genetic defects leading to these deficiencies have been determined.
- Some immunodeficiencies stem from developmental defects during embryogenesis and impair proper function of immune organs.
Types of Primary Immunodeficiencies
- Diagram illustrating various types of primary immunodeficiencies, categorized by affected immune components (phagocytic, humoral, cell-mediated, combined).
Primary Immunodeficiencies
- Defects' impact depends on the number and types of immune system components involved.
- Early hematopoietic defects affect the entire immune system.
- Reticular dysgenesis: a stem-cell defect impacting the development of all leukocytes leads to vulnerability to various infections.
- Defective phagocytic function results in bacterial susceptibility.
- More specific, less severe consequences result from defects in later-differentiated immune system components.
Primary Lymphoid Immunodeficiencies (B-cell deficiency disorders)
- Characterized by complete or selective absence of mature recirculating, B cells, plasma cells and immunoglobulins.
B-cell immunodeficiency Disorders
- Often involve recurrent bacterial infections, but viral and fungal infections are unaffected.
- Common causes: infections by encapsulated bacteria (staphylococci, streptococci, and pneumococci) needing antibodies for opsonization and clearance.
X-Linked Agammaglobulinemia (XLA)
- B-cell defect characterized by extremely low IgG levels and absence of other immunoglobulin classes.
- Defect in B-cell signaling, due to a defect in Bruton's tyrosine kinase (Btk) protein.
- Mutations in the BTK gene prevent BTK protein production and block B-cell development.
- Defective B cells remain in pre-B or immature stages, leading to lacking antibodies.
- Inherited in an X-linked recessive pattern, affecting primarily males.
T-cell Immunodeficiency Disorders
- A T-cell deficiency affects humoral and cell-mediated responses.
- Significant impact on cell-mediated immunity, causing a reduction in delayed-type hypersensitivity responses and cell-mediated cytotoxicity.
- Intracellular pathogens (Candida albicans, Pneumocystis carinii, Mycobacteria) vulnerability is common.
- Infections with viruses (cytomegalovirus, attenuated measles vaccine) can be life-threatening.
- Reduced antibody production after immunization.
Immune Disorders Involving the Thymus
- Several immunodeficiency syndromes related to thymus failure to develop.
- DiGeorge syndrome (congenital thymic aplasia) has a characteristic association with a deletion in chromosome 22 (22q11.2).
- Absence of the thymus, affecting T-cell function (helper, cytolytic, regulatory cells).
- Compromised immunity to viruses and fungi.
- Potential thymus transplantation to correct the defect, but heart disease can impede long-term survival.
Combined T and B-cell immunodeficiency Disorders
- Combined deficiencies of humoral and cell-mediated branches are the most severe immunodeficiency disorders.
- Onset of infections is early in infancy, and prognosis is poor without intervention to reconstitute the immune system; a high mortality rate is associated with these conditions.
- SCID (Severe Combined Immunodeficiency) involves defects in lymphoid development (T and B cells).
- Generally, very low circulating lymphocytes.
- Immunodeficiency leads to an incapacity to mount T-mediated immune responses; thymus development is often defective, and the few circulating T cells do not respond to stimulation.
Combined T and B-cell immunodeficiency disorders (SCID)
- SCID results in severe recurrent infections.
- SCID (Severe Combined Immunodeficiency) is often fatal in early years.
- Many agents like fungi or viruses, typically handled by T-cell immunity, impact infants.
- Maternal antibodies initially protect infants; these antibodies eventually deplete, leading to frequent infections.
Causes of Severe Combined Immunodeficiency (SCID)
- Often due to defects in genes essential for immune function, such as RAG genes, and cytokine receptors (IL-2, IL-4, IL-7, ...).
- Expression of class II MHC molecules, as well as CD40 Ligand, affect B-lymphocyte development.
Immunodeficiencies of the Myeloid Lineage
- Defects in myeloid cell lineage impact innate immune functions.
- Most myeloid defects lead to impaired phagocytic processes, causing recurrent microbial infections.
- Several steps in phagocytic processes can lead to immunodeficiency.
- Cell motility, adherence, phagocytosis, and killing by macrophages.
Quantitative deficiencies in neutrophils
- Neutrophils deficiency (agranulocytosis or neutropenia) can range from near absence of cells to reduced counts.
Congenital neutropenia
- Caused by genetic defects impacting myeloid progenitor stem cells.
- Reduced neutrophil production.
- May sometimes be an autosomal dominant condition.
Immunodeficiency of the Myeloid Lineage - Screening and Treatment
-
Testing involves complete blood counts (WBC), differentials, and x-rays (thymic shadow).
-
SCID diagnosis confirms very low/absent T-cells and impaired T-cell function.
-
T-cell receptor excision circles (TREC) deficiencies can be determined using PCR tests.
-
Treatment for antibody production disorders involve immunoglobulin replacement (pooled human gamma globulin).
-
Treatment options in general:
- Replacing missing proteins
- Replacing missing cells/lineages
- Correcting faulty genes
-
Bone marrow transplatation is a possible treatment, as well are other newer therapeutic options.
General Notes
- Several diagrams show the stages of lymphocyte development and the defects associated with immunodeficiency disorders.
- Information about the inheritance patterns and frequency of different types of immunodeficiency disorders is provided.
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Description
Test your knowledge on myeloid lineage immunodeficiencies and Severe Combined Immunodeficiency (SCID). This quiz covers key concepts, consequences of defects, and clinical implications related to these conditions. Challenge yourself with questions about genetic factors and infection susceptibility.
