Immunology - Immunodeficiencies Flashcards
Immunodeficiency that is mostly inborn (genetic) and often detected in infancy or childhood (sometimes adulthood)
Primary Immunodeficiency
Immunodeficiency that is acquired due to external factors
Secondary Immunodeficiency
Causes the inability of Pro-B cells to differentiate into Pre-B cells
X-linked agammaglobulinemia
In XLA, they can make a ______ chain variable region but not a ______ chain, so they are unable to make antibodies
heavy; light
Enzyme lacking in XLA
Tyr kinase
Clinical features of XLA
- Usually only affects males (X-linked)
- Recurrent respiratory infections call attention to the disease
T/F: Most bacteria causing recurring respiratory infections in patients with XLA are gram (+)
True
Diagnostic findings for XLA (3)
- B-cell absence or very decreased
- All immunoglobulins are depressed
- B-cell areas of lymphatic tissues are underdeveloped
XLA treatment
IVIG therapy
Immunological issues present with common variable immunodeficiency (3)
- defects in most classes of Ab secretion
- inability of Th cells to amplify Ab production
- reduced CT cell activity
A common feature of CVI is __________, usually involving all AB classes but sometimes only IgG
hypogammaglobulinemia
Clinical features of CVI
Resembles XLA - recurrent infections; also can have recurrent severe herpes infection
Diagnostic findings of CVI
- no other B-cell abnormality
- reduced immunoglobulins
- B-cell areas of lymphatic tissues are hyperplastic
Treatment of CVI
IVIG therapy
Most common primary immune deficiency
Isolated IgA deficiency - 1/600
Symptoms of patients with Isolated IgA deficiency?
Most asymptomatic
Patients with Isolated IgA deficiency have a Hx of recurrent…?
otitis media, sinusitis, bronchitis, pneumonia, GIT infections
Potentially deadly complication of Isolated IgA deficiency?
Anaphylaxis post-blood transfusion since transfused IgA antibodies recognized as foreign
Clinical pearl of IgA deficiency?
Serology for detecting celiac disease is based on IgA detection => IgA deficiency can lead to false negatives in celiac patients
Immunodeficiency where patients make IgM but have difficulty producing IgG, IgA, IgE?
Hyper-IgM Syndrome
What chromosome is Hyper-IgM Syndrome gene on?
X chromosome
In Hyper-IgM Syndrome, Th-cells can’t activate ______ and _______
B-cells and macrophages
Clinical features of hyper-IgM syndrome
- Recurrent purulent infection (CNS, resp tract, GIT)
- Many viral infections
- decreased neutrophil counts
Treatment for hyper-IgM syndrome?
IVIG and intense antibiotic prophylaxis
T-cell deficiency in which the 3rd and 4th pharyngeal pouches don’t develop
22q11 deletion (DiGeorge) Syndrome
With DiGeorges syndrome, you’re short on…?
A thymus parathyroid gland, some thyroid tissue - also heart and great vessel defects
Hypothesized that the _____ family of transcription factors is absent/doesn’t function, which is important for the transcription of _________.
T-box; brachial/pharyngeal arch development and large vessels
Because of thymic hypoplasia resulting in variable loss of T-cells, what is increased?
Increased fungal and viral infections, and autoimmunity
Clinical features of DiGeorge syndrome
- Cardiac abnormalities
- Craniofacial abnormalities
- Developmental delay
- Hypoparathyroidism
What electrolyte abnormality is associated with hypoparathyroidism?
Ca and P
Blood products can result in what for patients with DiGeorge syndrome?
graft-vs-host disease
What is graft-vs-host disease?
Mothers T-cells are transferred across the placenta occasionally, causing the mom’s lymphocytes to attack the baby’s tissue
A multitude of etiologies defined by recurrent, severe infections by a wide range of pathogens
Severe Combined Immunodeficiency
What is required in SCID patients to ensure death doesn’t occur at a young age?
Bone marrow transplant or stem cell therapies
In SCID, there are defects in both ______ and ______ immunity.
cell-mediated and humoral
What is X-linked SCID due to?
mutation in the gamma-chain of a variety of cytokine receptors
Signal transducing component of what receptors for which IL’s are affected?
IL-2, IL-4, IL-7, IL-9, IL-11, IL-15, IL-21
What is autosomal SCID due to?
mutation in adenosine deaminase and RAG mutations
What does adenosine deaminase mutation do?
causes accumulation of deoxyadenosine and its derivatives = toxic to rapidly dividing lymphocytes
What does a RAG mutation do?
Blocks B-cell and T-cell development
Pathological findings of SCID?
- small thymus with few lymphocytes
- depletion in T-cell areas of other lymphatic tissue
Most common complement defect?
C2 deficiency
Why do many people with C2 deficiency have no increased incidence of infection?
Alternative pathway is adequate for most cases
Autosomal dominant disorder less common than the complement deficiency disorders, that causes a deficit in C1 inhibitor?
Hereditary angioedema
Results of a deficit in C1 inhibitor?
- unchecked activation of classical pathway
- Increased bradykinin production
- increased activation of certain components of clotting cascade
Clinical features of hereditary angioedema
- episodic attacks that usually progressively become worse
- severe abdominal pain
- swelling of face, hands, legs, groin
Hereditary angioedema treatment
C1 inhibitor from blood products
Fungal infection of the lung
Pneumocytis jiroveci pneumonia
Reactivation of varicella zoster virus => painful rash
Herpes Zoster (shingles)
Conversion of latent TB to active form that usually affects the lungs
Tuberculosis
A chronic parasitic infection usually acquired through direct contact with contaminated soil
Stringyloidiasis
