Immune Deficiencies Flashcards
define immune deficiency
decrease in function or absence of one or more components of the immune system
- organs, tissues = spleen, thymus, bone marrow
- cells = T, B, NK, phagocytic cells
- proteins - complement, Igs, cell signalling, receptors, cytokines, etc.
classification of immune deficiencies
primary and secondary
primary immune deficincies
congenital
- rare!
secondary immune deficiencies
acquired
- viruses = HIV, EBV, congenital infections
- drugs
- radiation
- malignancy
etc,
general characteristics of immune deficiencies
- recurrent infections
- ealy age (4-6 mos)
- failure to thrive
- male predominance (X-linked)
- uncommon infections
- site specific infections (ear, sinus, resp, etc.)
- malignancy (CD8 cells not working)
- failure to respond to treatment
- autoimmune features
- variable in severity and clinical presentation
DiGeorge Syndrome deletion
deletion of q11.2 on chromosome 22
define Digeorge Syndrome
- impaired development of thymus, parathyroid gland, and heart
> discovered bc of heart defect (pouches in embryo)
clinical presentatioons of Digeorge syndrome
congenital heart disease
hypocalcemia
cleft palate
recurent infections
learning disabilities
autoimmunity
treatment of immune dysfunction
IVIg, prophylactic antibiotics, thymus transplant
common features of phagocytic cell disorders
- recurrent bacterial and fungal infections
- skin + soft tissues = gingivitis, thrush, hepatitis
- impaired wound healing
- pneumonia = S. pneumonia, Klebsiella. Serratia marcescens, Aspergillis sp.
Chediak Higashi (5)
- autosomal recessive mutation 1q42
- LYST lysosomal trafficking reg gene
- giant non-functional granules
- impaired intracellular killing by neuts, NK cells
- increase in lymphs
clinical presentation of Chediak Higashi
- gingivitis, S. aureus, Candida
- progressive neurological dysfunction
- reduced pigmentation (melanin granules not produced)
- light sensitivity sometimes?
accelerated phase of CH
fever
lymph infiltrates
thrombocytopenia
neutropenia
EBV
Treatment = HSCT
leukocyte adhesion deficiency (LAD)
- aut recessive 21q22
- missing B2 integrin (CD18)
- common to LFA-1, Mac-1, gp150/95 (CD11)
clinical presentations of LAD
- gram pos and neg infections
- viral response decreased
- absence of pus at wound site
- high WBC count
- variation in severity and outcomes
treatment of LAD
antibiotic prophylaxis and HSCT
Chronic Granulomatous Disease
X-linked (70%)
Aut Rec (30%)
- Xp21, 1q25, 16q24
- no NADPH oxidase
- decreased intracell killing
- inflammation and granulomas
clinical presentation of CGD
gingivitis, enlarged lymph nodes, granulomas
bacterial and fungal infections common
treatment of CGD
early culture and sensitivity
antibiotic prophylaxis
NADPH oxidase leads to superoxide (2O2) this leads to other reactive oxidative species such as …
hydroxyl radicals = OH
H2O2
hypochlorite (ClO-)
X-linked Agammaglobulinemia (XLA)
- missing Btk (cell signalling)
- no maturation of pre-B to B cells (no peripheral B cells)
- decreased IgG levels = absence of other classes
- systemic infections (URT, LRT, GI, deep tissues)
- S. pneumo, Haemophilus influenzae
treatment of XLA
IVIg with poor prognosis (late teens)
Granulopoiesis requires this
CD40L
most common primary immune deficiency
IgA deficiency
define IgA deficiency
varying levels of IgA = mild decrease to absent
- unknown cause
- associated with increase incidence of ITP, allergies, lupus, arthritis; IgG2, IgG4 deficiency
- increased infections of mucosal surfaces = URT, LRTm otitis media
treatment of IgA deficiency
antibiotics for bacterial infections
prevention is KEY = handwashing
X-linked hyper IgM
- Xq26
- no CD40L on T cells
- low IgG,A,E, but increased IgM
X-linked hyper IgM clinical presentations
neutropenia
thrombocytopenia
granulopoiesis requires CD40L
pneumonia early in life = pneumocystis, Cryptococcus, CMV
X-linked hyper IgM treatment
IVIg
presentation of SCID
- low, absent or non-functioning T cells
> B and NK cells may also be affected - several modes of inheritance
- severe immunodeficiency
- poor prognosis (<2 yrs if untreated)
- RARE
symptoms of SCID
failure to thrive
recurrent infections at 3-6 mos
- rash, diarrhea, skin and sinopulmonary infections, abscesses, poor wound healing
lymphopenia
hypothymia
common organisms that infect babies
Staph
Strep
Haemophilus
Candida
opportunistic infections that can lead to death for babies with SCID
C. albicans
Pneumocystis jirovecii
varicella
adenovirus
RSV
parainfluenza 3
CMV
EBV
causes of SCID
mutation affecting T cells with or without B and NK involvement
T-B-NK-
T-B+NK+
T-B-NK+
most common cause of SCID
SCID X1
- no gamma-c chain for IL-2,4,7,9,15,21
IL2Ry affected Xq13.1
T-B+NK-
B cells present but non-functional
Adenosine deaminase deficiency (ADA)
- autosomal recessive 20q13.11
- ADA function = adenosine to inosine
- if no enzyme = accumulation of deoxyadenosine triphosphate (dATP) = inhibits ribonucleotide reductase
= NO DNA synthesis - T-B-NK-
treatment for ADA
ADA and PEG injections given as co-treatment
IL-7Ra
- rare!
- autosomal recessive 5p13
IL-7R = gamma-c chain (same as IL-2,4,7,9,13) and alpha chain - T-B+NK+
- B and NK cells normal in number
causes of SCID
SCID-X1
ADA
IL-7a
JAK3
ZAP70
RAG1/RAG2
CD45
JAK3 as a cause of SCID
impaired signalling during hematopoiesis
T-B+NK-
ZAP 70 cause of SCID
impaired signalling of TCR
T-B+NK+ (normal T4+ but absent T8+)
RAG1/RAG2 cause of SCID
no TCR or immune globulin rearrangement
T-B-NK+
CD45 cause of SCID
impaired T and B cell receptor signal transduction
T-B-NK+
TREC PCR
- newborn metabolic screening
- T-cell receptor excision circles
> circular DNA fragments
> byproducts of TCR gene rearrangement (VDJ)
> low levels = decreased/absent T cells
this picks up all forms of SCIDs early
TREC PCR
supportive care for SCID
isolation
antibiotics
IVIg
irradiated blood products
treatment for SCID
hematopoietic stem cell transplant
factors that increases success of HSC transplant
early intervention <3.5 months
HLA identical
T cell depleted
no GVHD
lack of viral infection
gene therapy with IL-2a and ADA
8/9 children alive after nine years
4 developed leukemia; 1 death
oncogene LMO2 switched on
