Acquired and Innate Immune Deficiencies Flashcards Preview

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Flashcards in Acquired and Innate Immune Deficiencies Deck (35):

Discuss the warning signs of primary immunodeficiency.

- 4+ ear infections/yr
- 2+ sinus infections/yr
- 2+ pneumonias/yr
- failure to thrive
- recurrent deep skin abscesses
- persistent fungal (mouth/skin)
- IV antibiotics/2+ mon. w/o effect
- 2+ infections w/septicemia


B cell Immune Deficiency: common infections

• recurrent sinopulmonary (decreased IgA)
infections or sepsis
• usually encapsulated organisms
• chronic meningoencephalitis


B cell Immune Deficiency: lab tests

Ig levels
specific Ig titers
flow cytometry (B cell #)


B cell Immune Deficiency: examples

X-linked agammaglobulinemia
common variable immunodeficiency
selective IgA deficiency

Note: antibody deficiencies = 65% of innate immunologic disorders


T cell Immune Deficiency: common infections

• opportunistic infections
• recurrent + severe common infections
• failure to thrive, diarrhea


T cell Immune Deficiency: lab tests

CBC w/ differential
flow cytometry
T cell functional study
Ig levels


T cell Immune Deficiency: examples

DiGeorge syndrome
Wiskott Aldrich syndrome
SCID (B + T cell)


Phagocytic immune deficiency: common infections

• soft tissue abscesses or lymphadenitis
• infections w/catalase (+) organisms [S.
aureus, Serratia, Aspergillus]
• poor wound healing


Phagocytic immune deficiency: lab tests

CBC w/differential
PMN oxidative burst assay
flow cytometry


Phagocytic immune deficiency: examples

chronic granulomatous disease
leukocyte adhesion defect

Note: phagocytic deficiencies = 10% of primary immunodeficiencies


Complement immune deficiency: common infections

• recurrent disseminated Neisseria
• autoimmune disease
• bacterial sepsis


Complement immune deficiency: lab tests

CH50 measures
classical complement cascade


Complement immune deficiency: examples

terminal complement deficiency


Innate defects in immune system: common infections

• septicemia
• poor inflammatory response


Innate defects in immune system: lab tests

TLR signaling


Innate defects in immune system: examples

IRAK4 mutation
NEMO mutation
MyD88 mutation


Severe Combined Immunodeficiency (SCID)

18+ genes
- early detection + TX [newborn screening]
- ≠ normal T cell #s (look for TRECs = biomarker for T cell development)
- fatal within 1st year if no immune reconstitution (bone marrow transplant, gene therapy, PEG-ADA, thymic transplant)


DiGeorge Syndrome

22q11.2: microdeletion (1:3k-6k)
- classic triad: hypocalcemia, ♥ defect, thymic dysfunction
o Tetralogy of Fallot, decreased lymphocytes [lymphs made = good, do well]
o can do thymus transplant if thymus absent/incomplete


Common Variable Immunodeficiency (CVID)

~Relatively common (1:65k)

• Inherited primary immunodeficiency = bimodal presentation: 10 years and 30 years.

A defect in B cell differentiation and/or function
-Dx: marked decrease in IgG and at IgM or IgA; and has:
1) onset greater than 2 years old
2) absence of isohemagglutinins and/or poor response to vaccines (functional defect)
3) exclude defined causes of hypogammaglobulinemia

• Increased incidence of lymphoid malignancy, autoimmune disease, and atopy.
• Incidence of autoimmune disease in CVID patients = 25%
TX: IVIG (long-term), antibiotics, suppress immune system


Wiskott Aldrich syndrome (WAS)

Spectrum, X-linked recessive

- present w/ recurrent infections, decreased platelets, eczema => increased risk of autoimmunity + malignancy

- WAS protein expressed in blood cells = functions to modulate actin cytoskeleton
-actin cytoskeleton has role in immune function

o ID + TX: genotype-phenotype relationships + clinical scoring system

TX: IVIG, replace immune system w/ bone marrow transplant, gene therapy


X-linked lymphoproliferative disorder (XLP)

- mutation in SH2D1A gene (encodes SLAM-associated protein)
= involved in NK cell development + CD8+ responses in EBV infection

Typical presentation:
after EBV infection = fulminant liver failure
-due to severe immune dysregulation
--> fatal mononucleosis, hemophagocytic lymphohistiocytosis (HLH), lymphoma, aplastic anemia

Tx: bone marrow transplant, B cell depletion therapy early in EBV infection course


Chronic Granulomatous Disease (CGD)

X-linked + autosomal recessive

- disruption of NADPH oxidase complex function
o inability of PMNs to kill w/ ROS
o esp. catalase (+): S. aureus, Klebsiella, Aspergillus, Burkholeria, Serratia
- Increased WBCs, Increased Ig, (-) HIV

TX: antibiotics prophylaxis, IFN-γ prophylaxis, corticosteroids, bone marrow transplant, gene therapy


Define secondary or acquired immunodeficiency and distinguish from primary immunodeficiency

Primary immunodeficiencies are caused by defects which originate in the immune system itself.

Secondary immunodeficiencies are due to insufficiency of a supporting component of the immune system or an external or “secondary” depleting factor.


Explain that a large variety of conditions have a negative impact on immune function



Describe several examples of infections with worse outcomes in pregnant women

• Hepatitis A and B
• Influenza
• Herpes viruses
• Chlamydia/GC
• Listeria
• Campylobacter
• Tuberculosis
• Malaria


Explain the specific risk of infection with the use of TNF inhibitors.

Patients at risk for Granulomatous infections
Ex: mycobacterial infection, endemic fungal infections (histoplasmosis)


MOA of immune deficiency: aging

"Immune senescence"

Associated changes:
-progressive decrease in size and function of thymus
-decrease in suppressor cell function --> increase in auto reactivity
-changes in lymphocyte development and function = higher risk of latent virus reactivation (ex: VZV to cause shingles)


MOA of immune deficiency: malnutrition

-impaired cellular and humoral immunity

-MOS relates to:
Global metabolic disturbances
low levels of leptin
deficient intake of protein, fat, vitamins, minerals
deficiencies in zinc, iron, folate, pyridoxine, Vitamin A


MOA of immune deficiency: protein losing conditions

Ex: nephrotic syndrome or protein loosing enteropathy; IBD, Celiac's, burns, peritoneal dialysis

-can result in hypo-gammaglobulinemia


MOA of immune deficiency: pregnancy

Modulated immune condition:
-Progesterone = inhibits lymphocyte proliferation in vitro
-Uromodulin = pregnancy specific serum factor that inhibits B cell activity
-Depressed T cell response


MOA of immune deficiency: diabetes

-impair function of cells involved in cellular and/or humoral immunity
---MOST prominent: neutrophil dysfunction

-Type I: more immune dysregulation (autoimmune disease)
-Hyperglycemia = makes neutrophil function worse
-Other factors:
co-existing vascular disease = poor circulation/neuropathy = ulceration = poor wound healing = infection = difficulty clearing infection = complications
-CV compromise


MOA of immune deficiency: malignancy

-impaired cell-mediated and humoral responses
-bone marrow involvement = interferes with growth and development lymphocytes
-tumors may produce substances that interfere with lymphocyte development or function

B cell deficiencies have been noted in:
• Multiple myeloma
• Waldenstrom's macroglobulinemia
• Chronic lymphocytic leukemia
• Well differentiated lymphomas

T cell deficiencies have been noted in:
• Hodgkin's disease
• Advanced solid tumors


MOA of immune deficiency: rheumatologic disease

-immune dysregulation = autoimmunity
-increased susceptibility to infection

Granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis)


Summarize some important infections associated with the secondary immune deficiency of cirrhosis

-Shunting of portal blood so decreased ability of Kupffer cells to clear organisms
-hypocomplementemia = reduces serum opsonic activity
-reduced hepatic metabolism of endogenous gluccocorticoids = immune suppressive

Most common complications:
-bacterial peritonitis

Unusual infections associated with cirrhosis:
• Cryptococcal infection
• Candidal infection
• Infection with Vibrio vulnificus


Summarize some important infections associated with the secondary immune deficiency of diabetes

Common infections of increased frequency and severity:
• Pneumonias ( viral, strep pneumo)
• UTI ( including pyelonephritis)
• Cellulitis
• Diabetic foot infections
• Infections with candida (superficial) Vaginitis, thrush

Some unusual infectious complications of diabetes include:
• Infections with candida (deep)
• Rhinopulmonary zygomycosis (mucormycosis)
• Malignant otitis externa due to P. aeruginosa.