Immune Deficiencies Flashcards
Define Immune Deficiency
Decrease in function or absence of one or more components of the immune system:
- Organs and tissues
- Spleen, Thymus, Bone marrow - Cells
- T, B, NK, Phagocytic cells - Proteins
- Complement, immunoglobulins, cell signalling, receptors, cytokines etc.
Differentiate Primary vs Secondary immune deficiencies
- Primary
- congenital - Secondary
- acquired (HIV, EBV, drugs, radiation, malignancy, malnutrition, stress, splenectomy)
General Characteristics of Immune Deficiency
- recurrent infections from early age (4-6 months)
- malignancy
- failure to respond to treatment
Inheritance pattern of most Immune Deficiencies
X-linked (male predominance)
DiGeorge Syndrome: clinical presentation + treatment
- impaired development of thymus, parathyroid gland, and heart
= low T-dependent immune response, heart disease, hypocalcemia, cleft palate, learning disabilities, autoimmunity
Treatment: IVIg, thymus transplant, prophylactic antibiotics
Common Features of Phagocytic Cell Disorders
- recurrent bacterial and fungal infections
- affects skin + soft tissue (ie. gingivitis it’s, thrush, hepatitis)
- impaired wound healing
- pneumonia (S. pneumoniae, Klebsiella, Serratia marascens, Aspergillis sp.)
Chediak Higashi: Cause and lab results
- mutated LYST gene (lysosomal trafficking regulator)
= giant non-functional granules, impaired intracellular killing by neutrophils + NK cells
= increased lymphocytes to compensate
Chediak Higashi: clinical presentation + treatment
Clinical Presentation:
- gingivitis: S. aureus, C. albicans
- progressive neurological dysfunction
- reduced pigmentation (melanin from granules not produced)
Accelerated phase: fever, lymphocytes infiltrate, thrombocytopenia, neutropenia, EBV
Treatment: hematopoietic stem cell transplant
Leukocyte Adhesion Deficiency: Cause + Lab results
Cause:
- missing β2 Integrin subunit (CD18)
- common to LFA-1, Mac-1, gp150/95 (CD11)
Leukocyte Adhesion Deficiency: Clinical presentation + Treatment
Clinical Presentation:
- Gram pos and neg infections, viral response decreased - Absence of pus at wound site
- High wbc count
- Variation in severity and outcomes
Treatment:
- antibiotic prophylaxis
- hematopoietic stem cell transplant
Chronic Granulomatous Disease: Cause + Lab results
- Unable to produce NADPH oxidase
= Decreased intracellular killing (decreased super oxide = hydrogen peroxide), Inflammation and granulomas
Chronic Granulomatous Disease: Clinical presentation + Lab results
Clinical Presentation:
- Gingivitis, enlarged lymph nodes, granulomas
- Bacterial and fungal infections common
Treatment
- Early culture and sensitivity
- Antibiotic prophylaxis
X-Linked Agammaglobulinemia: Cause + Lab results + Treatment
- Missing Bruton’s tyrosine kinase (cell signaling)
= No maturation of pre-B to B cells (no peripheral B cells)
= decreasedIgG levels – absence of other classes
= Systemic infections (URT, LRT, GI, deep tissues) by S. pneumoniae and H. influenzae
Treatment: IVIg, but poor prognosis
X-linked Hyper IgM: Cause + Lab results
- No CD40L on T Cells
= Low IgG, IgA, IgE but increased IgM
= Neutropenia, Thrombocytopenia common (granulopoeisis requires CD40L)
X-Linked Hyper IgM: Clinical Presentation + Treatment
Clinical Presentation:
- Pneumonia early in life
- Pneumocystis, Cryptococcus, CMV
Treatment: IVIg
IgA Deficiency: Cause + Lab results
- unknown cause
= Varying levels of IgA (mild decrease to absent) - associated with IgG2 and IgG4 deficiency
IgA Deficiency: Clinical presentation + Lab results
- Increase incidence of ITP, allergies, lupus, arthritis
- Increased infections of mucosal surfaces (URT, LRT)
otitis media
Treatment: antibiotics for bacterial infections
NOTE: IVIg would not work; manufacturers remove IgA (mostly constituted of IgG = safer for people with IgA-deficiency)
Severe Combined Immunodeficiency Syndrome: Cause + Lab results
- Low, absent, or non-functioning T cells (hypothymia)
- B cells, NK cells may also be affected (lymphopenia)
Severe Combined Immunodeficiency Syndrome: Clinical Presentation
- poor prognosis (<2 years if untreated)
- severe immunodeficiency
= recurring infections (Rash, Diarrhea, Skin and sinopulmonary infections, Abscesses, Poor wound healing)
Adenosine Deaminase Deficiency: Cause + Lab results + Treatment
- affected ADA function for adenosine → inosine
= Accumulation of deoxyadenosine triphosphate
(dATP) inhibits ribonucleotide reductase
= No DNA synthesis (T- B- NK-)
Treatment: ADA and PEG injections
X-linked recessive SCID-X1: Cause + Lab results
- IL-2Ry affected
= no gamma-c chain for for IL-2,-4,-7,-9,-15, -21 receptors
= B cells present but non-functional (T- B+ NK-)
IL-7Rα: Cause + Lab results
- IL-7R: gamma-c chain (same as IL-2,-4,-7,-
9,-13 ) and α chain - B and NK cells normal in number
NOTE: issue with T cell that doesn’t affect other cells (T- B+ NK+)
Newborn Metabolic Screening:
T-cell Receptor Excision Circles (TREC) PCR:
- byproducts of TCR gene rearrangement (VDJ) in thymus = circular DNA fragments are amplified
- Low levels = decreased / absent T cells
NOTE: from heel poke/ blood spot
Management for T cell deficiencies
- isolation
- antibiotics
- IVIg
- irradiated blood products
Treatment for T cell Deficiency (2)
- hematopoietic stem cell transplant
- gene therapy (IL-2Rα and ADA)
Factors that increase HSC transplant for T cell Deficiency (5)
- early intervention ( <4 months)
- HLA-identical
- T cell depleted (only stem cells)
- no GVHD
- lack of viral infection
