Podcast
Questions and Answers
Severe combined immunodeficiency (SCID) invariably involves which type of immune cell?
Severe combined immunodeficiency (SCID) invariably involves which type of immune cell?
What is the underlying cause of Hemophagocytic Lymphohistiocytosis (HLH) related to perforin-granzyme killing?
What is the underlying cause of Hemophagocytic Lymphohistiocytosis (HLH) related to perforin-granzyme killing?
In cases of SCID, B cell function may be compromised due to:
In cases of SCID, B cell function may be compromised due to:
What age range is Hemophagocytic Lymphohistiocytosis (HLH) most commonly observed in, even though it can appear in people of all ages?
What age range is Hemophagocytic Lymphohistiocytosis (HLH) most commonly observed in, even though it can appear in people of all ages?
Signup and view all the answers
How many primary immunodeficiencies have had their gene(s) identified?
How many primary immunodeficiencies have had their gene(s) identified?
Signup and view all the answers
In Bare Lymphocyte Syndrome, a deficiency in MHC class I molecule expression is LEAST likely to directly result from:
In Bare Lymphocyte Syndrome, a deficiency in MHC class I molecule expression is LEAST likely to directly result from:
Signup and view all the answers
A patient with Bare Lymphocyte Syndrome type II is LEAST likely to exhibit which symptom?
A patient with Bare Lymphocyte Syndrome type II is LEAST likely to exhibit which symptom?
Signup and view all the answers
Bare Lymphocyte Syndrome type I is most directly associated with a mutation affecting:
Bare Lymphocyte Syndrome type I is most directly associated with a mutation affecting:
Signup and view all the answers
A diagnostic feature shared by both Bare Lymphocyte Syndrome type I and type II is:
A diagnostic feature shared by both Bare Lymphocyte Syndrome type I and type II is:
Signup and view all the answers
Which of the following best describes the primary treatment strategy for managing Bare Lymphocyte Syndrome type I?
Which of the following best describes the primary treatment strategy for managing Bare Lymphocyte Syndrome type I?
Signup and view all the answers
Which characteristic is typical of Hodgkin lymphoma's pattern of spread?
Which characteristic is typical of Hodgkin lymphoma's pattern of spread?
Signup and view all the answers
What is a key distinction between Hodgkin lymphoma and Non-Hodgkin lymphoma regarding the cells involved?
What is a key distinction between Hodgkin lymphoma and Non-Hodgkin lymphoma regarding the cells involved?
Signup and view all the answers
In which age group is Hodgkin lymphoma most commonly observed?
In which age group is Hodgkin lymphoma most commonly observed?
Signup and view all the answers
Which factor contributes to the less favorable prognosis observed in Non-Hodgkin lymphoma compared to Hodgkin lymphoma?
Which factor contributes to the less favorable prognosis observed in Non-Hodgkin lymphoma compared to Hodgkin lymphoma?
Signup and view all the answers
Which of the following is a possible origin site for Non-Hodgkin lymphoma?
Which of the following is a possible origin site for Non-Hodgkin lymphoma?
Signup and view all the answers
What is a common clinical manifestation in infants with African descent affected by persistent gastrointestinal infections, leading to nutrient absorption difficulties?
What is a common clinical manifestation in infants with African descent affected by persistent gastrointestinal infections, leading to nutrient absorption difficulties?
Signup and view all the answers
What is the underlying cause of Chronic Granulomatous Disease (CGD)?
What is the underlying cause of Chronic Granulomatous Disease (CGD)?
Signup and view all the answers
Which type of pathogens do individuals with Chronic Granulomatous Disease (CGD) have an increased susceptibility to?
Which type of pathogens do individuals with Chronic Granulomatous Disease (CGD) have an increased susceptibility to?
Signup and view all the answers
What is the primary defect in Leukocyte Adhesion Deficiency type 1 (LAD-1)?
What is the primary defect in Leukocyte Adhesion Deficiency type 1 (LAD-1)?
Signup and view all the answers
What is a distinctive clinical feature of Leukocyte Adhesion Deficiency type 1 (LAD-1)?
What is a distinctive clinical feature of Leukocyte Adhesion Deficiency type 1 (LAD-1)?
Signup and view all the answers
What metabolic process is impaired in Leukocyte Adhesion Deficiency type 2 (LAD-2)?
What metabolic process is impaired in Leukocyte Adhesion Deficiency type 2 (LAD-2)?
Signup and view all the answers
What is the consequence of defective platelet aggregation in individuals with Leukocyte Adhesion Deficiency type 3 (LAD-3)?
What is the consequence of defective platelet aggregation in individuals with Leukocyte Adhesion Deficiency type 3 (LAD-3)?
Signup and view all the answers
Deficiencies in which complement components are associated with a higher risk of recurrent Neisseria infections?
Deficiencies in which complement components are associated with a higher risk of recurrent Neisseria infections?
Signup and view all the answers
What is the primary outcome of C1INH deficiency?
What is the primary outcome of C1INH deficiency?
Signup and view all the answers
Which factor is the MOST common non-biological cause of secondary immunodeficiency?
Which factor is the MOST common non-biological cause of secondary immunodeficiency?
Signup and view all the answers
What is the underlying cause of Chronic Lymphocytic Leukemia (CLL)?
What is the underlying cause of Chronic Lymphocytic Leukemia (CLL)?
Signup and view all the answers
What is the primary consequence of Acute Myeloid Leukemia (AML) on normal blood cell development?
What is the primary consequence of Acute Myeloid Leukemia (AML) on normal blood cell development?
Signup and view all the answers
In Multiple Myeloma, what is the effect of the accumulation of malignant plasma cells within bone?
In Multiple Myeloma, what is the effect of the accumulation of malignant plasma cells within bone?
Signup and view all the answers
What is the primary cause of renal failure in individuals with Multiple Myeloma?
What is the primary cause of renal failure in individuals with Multiple Myeloma?
Signup and view all the answers
Patients with C3 deficiency have increased susceptibility to what kind of pathogens?
Patients with C3 deficiency have increased susceptibility to what kind of pathogens?
Signup and view all the answers
In Hemophagocytic Lymphohistiocytosis (HLH) caused by a defect in T cells or NK cells, what is the primary driver of the immune response?
In Hemophagocytic Lymphohistiocytosis (HLH) caused by a defect in T cells or NK cells, what is the primary driver of the immune response?
Signup and view all the answers
Which of the following is a typical symptom observed in patients with Hemophagocytic Lymphohistiocytosis (HLH)?
Which of the following is a typical symptom observed in patients with Hemophagocytic Lymphohistiocytosis (HLH)?
Signup and view all the answers
What is the underlying cellular mechanism impaired in CTLs and NK cells due to the mutation described?
What is the underlying cellular mechanism impaired in CTLs and NK cells due to the mutation described?
Signup and view all the answers
Which of the following is a common treatment strategy for Hemophagocytic Lymphohistiocytosis (HLH)?
Which of the following is a common treatment strategy for Hemophagocytic Lymphohistiocytosis (HLH)?
Signup and view all the answers
What is the primary defect in Selective IgA Deficiency?
What is the primary defect in Selective IgA Deficiency?
Signup and view all the answers
Which of the following is a typical clinical manifestation of Selective IgA Deficiency?
Which of the following is a typical clinical manifestation of Selective IgA Deficiency?
Signup and view all the answers
In Selective IgA Deficiency, what is the typical status of peripheral B cell numbers?
In Selective IgA Deficiency, what is the typical status of peripheral B cell numbers?
Signup and view all the answers
A patient is diagnosed with Selective IgA Deficiency. Which of the following conditions are they more prone to developing?
A patient is diagnosed with Selective IgA Deficiency. Which of the following conditions are they more prone to developing?
Signup and view all the answers
What is the primary function of Activation-Induced Cytidine Deaminase (AID) in B cells?
What is the primary function of Activation-Induced Cytidine Deaminase (AID) in B cells?
Signup and view all the answers
Which of the following is a typical clinical manifestation observed in patients with Activation-Induced (Cytidine) Deaminase (AID) Hyper IgM Syndrome 2 (HIGM2)?
Which of the following is a typical clinical manifestation observed in patients with Activation-Induced (Cytidine) Deaminase (AID) Hyper IgM Syndrome 2 (HIGM2)?
Signup and view all the answers
What is a common treatment for patients with Activation-Induced (Cytidine) Deaminase (AID) Hyper IgM Syndrome 2 (HIGM2)?
What is a common treatment for patients with Activation-Induced (Cytidine) Deaminase (AID) Hyper IgM Syndrome 2 (HIGM2)?
Signup and view all the answers
How does Hyper IgM Syndrome type 1 (HIGM1) differ from Hyper IgM Syndrome type 2 (HIGM2) in terms of the primary immune cell affected?
How does Hyper IgM Syndrome type 1 (HIGM1) differ from Hyper IgM Syndrome type 2 (HIGM2) in terms of the primary immune cell affected?
Signup and view all the answers
In patients with Hyper IgM syndrome, even if IgM levels are within the normal range, what ratio between IgM and IgG may indicate the presence of the syndrome?
In patients with Hyper IgM syndrome, even if IgM levels are within the normal range, what ratio between IgM and IgG may indicate the presence of the syndrome?
Signup and view all the answers
What is the underlying cause of Bare Lymphocyte Syndrome (BLS) Type I?
What is the underlying cause of Bare Lymphocyte Syndrome (BLS) Type I?
Signup and view all the answers
In Bare Lymphocyte Syndrome (BLS), which type, I or II, is more common and what is its primary defect?
In Bare Lymphocyte Syndrome (BLS), which type, I or II, is more common and what is its primary defect?
Signup and view all the answers
Which of the following genetic defects leads to HIGM 5?
Which of the following genetic defects leads to HIGM 5?
Signup and view all the answers
Flashcards
SCID
SCID
Severe combined immunodeficiency; affects T cells and may involve B and NK cells.
Primary immunodeficiencies
Primary immunodeficiencies
Disorders affecting the immune system, with 430 known types; 343 genes identified.
HLH
HLH
Hemophagocytic lymphohistiocytosis; a condition involving excessive immune cell activity.
Causes of HLH
Causes of HLH
Signup and view all the flashcards
T cell dependency
T cell dependency
Signup and view all the flashcards
CTLs response
CTLs response
Signup and view all the flashcards
Hemophagocytic Lymphohistiocytosis
Hemophagocytic Lymphohistiocytosis
Signup and view all the flashcards
Symptoms of HLH
Symptoms of HLH
Signup and view all the flashcards
Treatment for HLH
Treatment for HLH
Signup and view all the flashcards
Selective IgA Deficiency
Selective IgA Deficiency
Signup and view all the flashcards
Symptoms of IgA Deficiency
Symptoms of IgA Deficiency
Signup and view all the flashcards
IgA treatment challenges
IgA treatment challenges
Signup and view all the flashcards
Clinical manifestation of HLH
Clinical manifestation of HLH
Signup and view all the flashcards
Hyper IgM Syndrome 2
Hyper IgM Syndrome 2
Signup and view all the flashcards
Activation-Induced Deaminase (AID)
Activation-Induced Deaminase (AID)
Signup and view all the flashcards
Symptoms of HIGM 2
Symptoms of HIGM 2
Signup and view all the flashcards
Treatment for Hyper IgM Syndrome 2
Treatment for Hyper IgM Syndrome 2
Signup and view all the flashcards
HIGM 1 syndrome
HIGM 1 syndrome
Signup and view all the flashcards
HIGM 3 syndrome
HIGM 3 syndrome
Signup and view all the flashcards
Normal Ig levels in Hyper IgM
Normal Ig levels in Hyper IgM
Signup and view all the flashcards
Bare Lymphocyte Syndrome
Bare Lymphocyte Syndrome
Signup and view all the flashcards
MHC Class I Defect
MHC Class I Defect
Signup and view all the flashcards
MHC Class II Defect
MHC Class II Defect
Signup and view all the flashcards
Clinical Symptoms of Bare Lymphocyte Syndrome
Clinical Symptoms of Bare Lymphocyte Syndrome
Signup and view all the flashcards
Treatment for Bare Lymphocyte Syndrome
Treatment for Bare Lymphocyte Syndrome
Signup and view all the flashcards
Non-Hodgkin Lymphoma
Non-Hodgkin Lymphoma
Signup and view all the flashcards
Hodgkin Lymphoma
Hodgkin Lymphoma
Signup and view all the flashcards
Reed-Sternberg Cells
Reed-Sternberg Cells
Signup and view all the flashcards
Hodgkin Lymphoma Prognosis
Hodgkin Lymphoma Prognosis
Signup and view all the flashcards
Non-Hodgkin Lymphoma Prognosis
Non-Hodgkin Lymphoma Prognosis
Signup and view all the flashcards
Chronic Granulomatous Disease
Chronic Granulomatous Disease
Signup and view all the flashcards
Symptoms of Chronic Granulomatous Disease
Symptoms of Chronic Granulomatous Disease
Signup and view all the flashcards
Leukocyte Adhesion Deficiency (LAD)
Leukocyte Adhesion Deficiency (LAD)
Signup and view all the flashcards
LAD-1 Cause
LAD-1 Cause
Signup and view all the flashcards
Symptoms of LAD-1
Symptoms of LAD-1
Signup and view all the flashcards
LAD-2 Cause
LAD-2 Cause
Signup and view all the flashcards
Symptoms of LAD-2
Symptoms of LAD-2
Signup and view all the flashcards
LAD-3 Cause
LAD-3 Cause
Signup and view all the flashcards
Symptoms of LAD-3
Symptoms of LAD-3
Signup and view all the flashcards
C1, C2, or C4 Deficiencies
C1, C2, or C4 Deficiencies
Signup and view all the flashcards
C5-C9 MAC Deficiencies
C5-C9 MAC Deficiencies
Signup and view all the flashcards
C3 Deficiency
C3 Deficiency
Signup and view all the flashcards
Secondary Immunodeficiencies
Secondary Immunodeficiencies
Signup and view all the flashcards
Common Causes of Secondary Immunodeficiencies
Common Causes of Secondary Immunodeficiencies
Signup and view all the flashcards
Neoplasms in the Immune System
Neoplasms in the Immune System
Signup and view all the flashcards
Study Notes
Learning Objectives
- Students will compare and contrast primary and secondary immunodeficiencies.
- Students will describe selected immunodeficiency disorders.
- Students will identify the clinical features and underlying immune mechanisms of selected immunodeficiency disorders.
- Students will describe treatment options for selected immunodeficiency disorders.
- Students will describe selected cancers associated with immune deficiencies.
Immune System Disorders
- Immune system disorders can include absences (immunodeficiencies), excesses (uncontrolled proliferations - neoplasias), loss of tolerance (autoimmune disease).
Immunodeficiencies
- The hallmark of these disorders is an increased susceptibility to infections.
- Frequent or chronic infections often more severe than normal.
- Infections cause by opportunistic or commensal organisms are often seen.
- Infections often do not respond normally to treatment.
- Other issues might include anemia, arthritic pain, autoimmune disease (in ~25% of cases), neoplasia, or growth retardation
Primary Immunodeficiencies (PIs)
- These are congenital conditions (present at birth).
- Caused by a genetic defect.
- ~ 1 in 500 people with a PI.
- Due to the redundancies of the immune system, only about 1 in 10,000 people develop significant disease associated with PI.
Primary Immunodeficiencies (continued)
- Primarily manifest in childhood.
- Can be categorized by the type of immune function affected (e.g., humoral, complement, cellular function).
- Severe Combined immunodeficiency (SCID) is a family of disorders affecting multiple parts of the immune system.
- SCID always involves T cells, but may also affect B cells or NK cells.
- The defect can be in T cells, but can affect B cell function due to their dependence on T cell 'help'.
Most Common Types of Primary Immunodeficiencies
- Antibody (50%)
- Cellular (10%)
- Phagocytic (18%)
- Complement (2%)
- Combined (20%)
- There are 430 known primary immunodeficiencies with genetic causes identified in 343 of them.
Hemophagocytic Lymphohistiocytosis (HLH)
- A primary/secondary condition involving genetic or acquired malfunctions (infectious agents, cancers, immunodeficiencies, drugs).
- Most common in infants (birth – 18 months), but can occur in children and adults.
- Characterized by an excess of macrophages in the blood, affecting the lymphatic system.
- Mutations in genes involved in perforin-granzyme killing pathway of CTLs and NK cells cause HLH.
- Often leads to the activation of macrophages resulting in excessive inflammation (systematic inflammatory syndrome), infections or viral infections, anemia, low platelet and neutrophil counts, and splenomegaly (potentially fatal).
HLH Treatment
- Methotrexate and Prednisone (neurological implications)
- Anti-IFN-γ
- Etoposide
- Dexamethasone
- Cyclosporine A
- Bone marrow transplant
Selective IgA Deficiency
- AKA: dysgammaglobulinemia
- The most prevalent primary immunodeficiency.
- Defect in B cell development into IgA-secreting plasma cells.
- IgA genes are normal, but the defect lies in the differentiation process after clonal proliferation.
- Individuals with Selective IgA Deficiency commonly have recurrent infections, particularly in mucosal tissues (respiratory, GI tract).
- They may also be more prone to allergies, asthma, or Rheumatoid Arthritis (RA).
- Treatment involves antibiotics as needed for infections.
Activation-Induced (Cytidine) Deaminase (AID) Hyper IgM Syndrome 2
- Caused by a mutation in the AID enzyme.
- AID is responsible for class-switch recombination in B cells within follicles.
- The enzyme is induced upon CD40-CD40L interactions with T helper cells.
- There are multiple forms of Hyper-IgM, but Hyper IgM 2 is the common one.
- Patients often exhibit normal circulating CD19+ B cells but lack switched isotypes.
- IgM levels can be elevated, but are usually within a normal range.
- Hemolytic anemia is a common clinical finding.
- Treatment involves IVIg and antibiotics as needed.
Other Causes of Hyper-IgM Syndrome
- HIGM1 (X-linked) - CD40L mutations (T cell defect), leading to a SCID, as this cell defect is in a T-cell.
- HIGM3 - CD40 mutations (B cell defect).
- HIGM4 - Break in the switch region upstream of the Cμ gene (B cell defect).
- HIGM5 - Uracil DNA Glycosylase (UNG) (B cell defect).
Secondary Immunodeficiencies
- Patients are born with a healthy immune system.
- The deficiency arises from a subsequent factor or occurrence reducing the immune response.
- Can arise due to patient health statuses such as age, stress, alcohol misuse, smoking, lack of sleep.
- Some possible biological causes include viruses, diabetes or cancer.
- Many therapies suppress immunity (e.g., monoclonal antibodies [mAb], small molecule inhibitors).
Common Causes of 2ndary Immunodeficiencies
- Malnutrition is the most common non-biological cause of decreased immunity.
- AIDS due to HIV infection is the most common biological cause of decreased immunity
Neoplasias (immune system cancers)
- Cancers of the immune system are sometimes classified as leukemias or lymphomas.
- Leukemias involve the proliferation of individual immune cells (lymphoid or myeloid).
- Lymphomas involve the proliferation of a mass of immune cells.
Types of Leukemia
- Acute lymphoblastic leukemia (ALL)
- Acute myeloid leukemia (AML)
- Chronic lymphoblastic leukemia (CLL)
- Chronic myeloid leukemia (CML)
Acute Lymphoblastic Leukemia (ALL)
- Characterized by dysregulated proliferation and clonal expansion of lymphoid progenitor cells (primarily B cells).
- Most common malignancy in children.
- Can occur in children and adults.
- Signs and symptoms might include anemia, pale skin, headaches, enlarged lymph nodes, liver, spleen; and bleeding or bruising.
Chronic Lymphocytic Leukemia (CLL)
- Typically involves the proliferation of mature circulating B cells that cannot undergo apoptosis due to genetic alterations.
- Accounts for about one-third of all leukemias.
- Results in lower antibody responses.
- Most common in adults (55+).
Acute Myeloid Leukemia (AML)
- A malignant proliferation of immature granulocyte precursor cells.
- Malignant cells crowd out normal cell development within the bone marrow.
- Leads to decreased white blood cell counts and increased infections.
- May result in lowered red blood cell counts and platelets, which can cause anemia and bleeding.
- Occurs in children and adults.
Chronic Myeloid Leukemia (CML)
- A malignant disorder of granulocytes (white blood cells).
- Also involves megakaryocytes (platelet precursors) and erythrocytes.
- Occurs mostly in adults.
Multiple Myeloma (plasmacytoma)
- A malignant condition with differentiated B lymphocytes (plasma cells).
- Characterized by bone destruction and "punched-out" holes (especially in the spine and skull), which are diagnostic.
- Normal B cell production is impaired.
- Usually found in older adults and is more frequent in African Americans and Native Pacific Islanders.
- Often leads to renal failure due to the presence of Bence-Jones proteins (overproduced light chains) in the urine that cannot be filtered.
Hodgkin Lymphoma
- Typically spreads predictably from one lymph node to another.
- Characterized by the presence of Reed-Sternberg cells (a specific type of lymphocyte).
- Often begins in the neck region (cervical lymph nodes).
- May arise from previous Epstein Barr Virus (EBV) infections.
- Most common in teens and young adults.
- Usually treatable with a high survival rate.
Non-Hodgkin Lymphoma
- May involve B cells or T cells and is typically more aggressive and less predictable than Hodgkin lymphoma.
- Can spread to areas beyond the lymph nodes.
- Usually is at an advanced stage when diagnosed.
- Survival rates are lower when diagnosed at an advanced stage.
Phagocytic Disorders
- Chronic Granulomatous Disease (CGD)
- Oxidative burst dysfunction in phagocytic immune cells (e.g., neutrophils, macrophages) which results in pathogens surviving within the phagocyte
- Chronic infections, oral/gum disease, respiratory and urinary infections, and abscess formation
- Prophylactic antibiotics or antifungal drugs are required.
- Leukocyte Adhesion Deficiency (LAD)
- Impaired adhesion between leukocytes and vascular endothelium
- Neutrophilia, frequent infections and soft-tissue infections, delayed umbilical cord separation, and poor wound healing.
- Infections may also target gums → loss of teeth, and lack of pus formation.
Complement Disorders
- C1, C2, or C4 deficiency
- Little to no increased infections associated with immune complex formation. (RA, SLE, vasculitis)
- C5-C9 MAC deficiency
- More frequent, recurrent and invasive infections by Neisseria species (meningitidis and gonorroheae).
- C3 deficiency
- Increased susceptibility to encapsulated bacterial pathogens (most severe).
- Complement regulatory proteins deficiency (e.g., C1-INH deficency)
- Abnormal complement activation. (Uncontrolled C4 or C2 activation → edema or angioedema.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on severe combined immunodeficiency (SCID) and Hemophagocytic Lymphohistiocytosis (HLH). This quiz covers essential aspects such as immune cell involvement, underlying causes, and specific syndromes. Challenge your understanding of these disorders and their implications in immunology.
