Immunodeficiencies Flashcards
Name 2 innate immunity defects
- Chronic granulomatous disease
- Leukocyte adhesion deficiency
Chronic granulomatous disease mechanism
NADPH oxidase complex deficiency = less superoxide
Less respiratory burst = granuloma formation
Tests for chronic granulomatous disease
Dihydrorhodamine flow cytometry DHR 123
Nitro-blue
Chronic granulomatous disease signs & symptoms (5)
- Osteomyelitis
- Lymphadenopathy
- Pneumonia
- Abscesses (liver, visceral)
- Granulomas: skin, GI, GU = obstruction
Chronic granulomatous disease lab findings (2) (Ig, RBC)
HYPERgammaglobulinemia
Anemia
Chronic granulomatous disease infections
CATALASE +
- S. aureus
- B.cepacia
- Nocardia spp.
- Aspergillus
- Candida
CATs have BeeN PLACESS = CATalase, Burkholderia, Nocardia, Pasteurella, Listeria, Aspergillus, Candida, E.coli, Staphylococcus, Serratia
Chronic granulomatous disease treatment
Prophylactic antibiotics (TMP-SMX) or antifungals (itraconazole)
Glucocorticoids
IFN-y therapy
Severe: stem cell transplant
Effect of NADPH oxidase
Converts to NADP+ —> makes superoxide O2- —> H2O2 —> broken down by catalase into H20 and O2
Therefore: more catalase = more breakdown of H2O2 = less H2O2 = weak respiratory burst
Chronic granulomatous disease hereditability
X-linked or AR
LAD mechanism
LFA-1/CD18 abscence
Beta-2 integrin for neutrophil adhesion
Phagocytes are trapped in circulation
LAD hereditability
AR
LAD signs & symptoms (4)
- MOUTH skin and mucosa
- Delayed umbilical cord separation >10 days
- Omphalitis
- Impaired wound healing
LAD lab findings (1)
Neutrophilia
LAD infections
Bacterial
Non-suppurative
- S.aureus
- P.aureginosa
- Klebisella
LAD treatment
Prevent infection
Bone marrow transplant
Prophylactic antibiotics
Life expectancy without tx = extremely short
LAD types
LAD1: b2 deficiency
LAD2: Sialyl-Lewis X deficiency (rolling)
LAD3: b1, b2, and b3 deficiency = no leukocyte activation nor platelet binding (HEMORRHAGIC)
Humoral defects (3)
- X-linked agammaglobulinemia (XLA)
- Hyper IgM
- CVID
XLA mechanism
BTK deficiency = no mature B cells
Stop in pre-B or pro-B
XLA signs & symptoms, age they start
START IN 3-6 MONTHS
- Lymphoid hyperplasia
- Severe, recurrent pyogenic infections —> pneumonia, otitis media, bronchitis, sinusitis
XLA infections
ENCAPSULATED bacteria
- S.pneumoniae
- N.meningitidis
- H.influenzae
ENTEROVIRUS
- Coxsackie
- Polio
GIARDIA LAMBLIA
XLA treatment
IVIG monthly
Prophylactic antibiotics
Which immunodeficiencies can’t receive live vaccines? Ex. Polio
XLA
SCID
Hyper IgM mechanisms (2)
CD40L deficiency
- Less in Th cells = disrupt B cell class switch
AID dysfunction
- Affect IgH chain recombination
- Increase germinal centers = GIANT
Hyper IgM signs & symptoms (4) and age
CHILDHOOD
- Recurrent severe pyogenic infections
- Respiratory
- Enteritis
- Hepatitis
Hyper IgM lab findings
Neutropenia
IgM only
Hyper IgM infections
SINOPULMONARY OPPORTUNISTIC
- P.jirovecci
- Histoplasma
- Cryptosporidium = chronic diarrhea
- CMV = pneumonia & hepatitis
- S.pneumoniae
- Cryptococcus
- Mycobacteria
- Giardia lamblia
Hyper IgM treatment (4)
IVIG
Prophylactic antibodies
Recombinant G-CSF
Stem cell transplant
Hyper IgM heritability
XR
CVID mechanism
Phenotypically normal B cells can’t SURVIVE
= less plasma and memory cells
TACI
MHC HLA: DQ2, DR17, DR7, B8
CVID signs & symptoms (4) and age
20-40 years
- Recurrent pyogenic: SINOPULMONARY, meningitis
- Lymphoma risk
- Autoimmune disorder risk
- Less vaccine response
CVID lab findings
HYPOgammaglobulinemia
CVID infections (4)
GIARDIA LAMBLIA
Mycoplasma
Congenital: rubella, CMV, T.gondii
Recurrent HZV
CVID treatment
Prophylactic antibodies
IVIG
Humoral deficiency most common manifestations (3)
Sinusitis
Bronchitis
Pneumonia
Encapsulated pyogenic bacteria
SCID mechanisms (4)
NK+ = RAG 1/2 = defective VDJ
B+ = IL-2R gamma chain (most common)
All - = Adenosine deaminase ADA = toxic metabolites of deoxyadenosine and dATP
B+NK+ = IL-7Ra defect
What do all SCID mutations have in common in their genotype
T-
SCID signs and symptoms (4) and age
NORMAL AT BIRTH, 4-6 month onset
Severe, recurrent
- Bacterial diarrhea, chronic
- Chronic thrush
- Absent lymph nodes
- Inadequate growth
SCID lab findings (4)
- Less TRECs (excision circles)
- Lymphopenia <300-500
- Absent germinal centers
- No thymic shadow
SCID infections
ALL
Bacterial
Viral
Protozoal
SCID treatment
IVIG
PCP prophylaxis
HSCT
SCID red flags
Avoid live vaccines
Fatal if not tx within year 1
T-B-NK+ mechanism
RAG 1/2 defect
T-B+NK- mechanism
IL-2R gamma chain
T-B-NK- mechanism
Adenosine deaminase ADA deficiency
T-B+NK+ mechanism
IL-7Ra defect
Omenn symdrome
SCID
Onset before 3mo.
- Erythroderma
- Adenopathy
- Hepatosplenomegaly
- Inadequate growth
X-linked immunodeficiencies
- Chronic granulomatous disease
- XLA
- Hyper IgM
- IL-2R gamma SCID
TACI deficiency effect
No mature B cells
Genotype for LESS CD27+ memory B cells
CD40 and CD40L
Genotype for normal CD27+ memory B cells but decrease of IgG
AID, UNG
