Primary Immune Deficiencies Flashcards
most prominent type of primary immune deficiency
a majority of the cases are due to humoral defects with immunoglobulins and B cells
common signs/symptoms of humoral deficiency
pyogenic infections with recurrent otitis media, sinusitis, pneumonia
frequent viral infections, chronic diarrhea
too many infections in kids?
4 courses of antibiotics in a year
too many infections in adults?
2 courses of antibiotics in a year
too many ear infections after age 4?
4 in a year, less because physiology changing
Agammaglobulinemia cause
defect in B cell development, germinal center formation is defective
often see under development of lymphoid tissue like nodes, spleen, tonsils
X linked Agammaglobulinemia etiology and name
85% of agammglobulinemias, called Brutons agammaglobulinemia
due to problem with B cell tyrosine kinase
BTK receptor in Brutons Agammaglobulinemia
part of the pre B cell receptor that leads to a phosphorylation and pathway to stimulate B cell maturation
one protein in a complex so other proteins can have problems too in the same complex
XLA cellular signs
IgG less than 100 mg/dl
B cells less than 2% of total lymphocytes
Normal T cell function and number
Hyper IgM syndrome
problems with class switching of antibodies have regular number of B cells but elevated levels of IgM and low IgE/A/G
IgA deficiency information
IgA less than 5-7mg/dl
most common primary immunodeficiency
Usually asymptomatic
Common Variable Immunodeficiency (CVID) cell signs
most common symptomatic primary immunodeficiency
low IgG/A/M, reduced specific antibody responses to previous infections or vaccines
Cause of Common Variable Immunofdeficiency
usually a gene involved in the development or maturation of B cells
Common Variable Immunodeficiency symptoms
recurrent infections, mainly sinusitis, and pneumonia
life threatening infections
poor response to vaccines
Risks associated with Common Variable Immunodeficiency
granulomatous diseases, autoimmune disorders, splenomegaly, and malignancies like lymphoma
Specific Antibody Deficiency cell signs
normal antibody levels, normal T and B cell number and function
Specific Antibody Deficiency symptoms
usually have recurrent sinopulmonary infections, impaired antibody response to encapsulated bacteria
most common deficiency is the specific antibody deficiency to pneumococcus from vaccine (polysaccharide)
Some Killer Have Pretty Nice Capsules (encapsulated mnemonic
Step pneumo and pyogenes Staph Aureus Klebsiella Haemophilus Influenzae Pseudomonas aeruginosa Neisseria meningitidis Cryptococcus neoformas
Transient hypogammaglobulinemia in infancy symptoms
recurrent sinopulmonary infections
Transient hypogammaglobulinemia in infancy cell signs
low IgG but normal specific antibodies due to slowed response
normal lymphocyte count and function
resolves by age 4, onset after IgG maternal lost
Tests to run if speculating humoral deficiency?
CBC with differential Age adjusted quantitative immunoglobulins Specific antibody titers Complement pathway CH50, AH50 Lymphocyte markers (CD19)
common Specific antibody production tests
tetanus and diphtheria proteins and isohemagglutinins
Prevnar vaccine for pneumococcal
conjugate vaccine given to infants that combines proteins from 13 common penuomoccocal strands
Pneumovax polysaccharide vaccine for pneumococcal
combines 23 common polysaccharides from different pneumococcal strands
common clinical infections withT cell dysfunction
infections with intracellular organisms like viruses, protozoa, mycobacterium, fungal, encapsulated bacteria
Common clinical symptoms with T cell dysfunction
lack of growth, cant recall antigens, thrush, eczema, hair loss, eosinophilia, increased B cell malignancies
Chronic Mucocutaneous Candidiasis symptoms
result in decreased cell mediated immunity against Candida species
chronic non invasive infections usually cause changes in skin, nails and mucosal membranes
SCID age of onset
typically between 4-6 months of age
SCID signs of disease
severe persistent infections, oral thrush, chronic diarrhea and lack of growth
SCID cellular cause
super low numbers of T cells…sometimes like B or Nk cells too
will not respond to T cell mitogen test
IL-2R gamma chain SCID cellular effects, mode of inheritance and defect
T cells low, B cells regular and NK cells low
X linked
defect in common gamma chain that makes interleukins
Adenosine Deaminase Deficiency in SCID cellular effects, mode of inheritance and defect
T, B, and NK cells are low
AR
accumulation of toxic purine nucleosides…positive is you can give the enzyme to fix this
RAG1/2 deficiency in SCID cellular effects, mode of inheritance and defect
T and B low, NK normal
AR
defective VDJ recombination
TRECs definition
T cell receptor excision circles are made when the TCR complex is being produced
the TRECs are a sign of thymic function and T cell production…so if they are there it is unlikely to have SCID but if they are not there in a screening then you may have SCID
TRECs role in screening for SCID
the TRECs are a sign of thymic function and T cell production…so if they are there it is unlikely to have SCID but if they are not there in a screening then you may have SCID
Omenn Syndrome symptoms and cellular problems
commonly issues with RAG genes, is a subset of SCID called Leaky SCID
Low to normal number of T cells
onset about 3 months (earlier than SCID)
Symptoms include lymphadenopathy, heptosplenomegaly, diarrhea, lack of growth, elevated IgE and eosinophilia
Wiskott aldrich syndrome and symptoms
involved with actin polymerization andaffects various lymphocyte functions
Eczema, small platelets, low MPV, low IgG and IgM
Regular IgA and IgE
high risk of autoimmune and malignancy
T cell immunodeficiency Tests
CBC with differential mitogen testing Antigen reactivity testing DTH to candida nucleic acid enzyme assays
gene linkage of CGD
X linked and AR for phox genes
Hyper IgE syndrome signs and symptoms
recurrent staph abscesses is most common
sinopulmonary infections and sever eczema
retained primary teeth, recurrent candida, recurrent bone fractures, high IgE, peripheral eosinophilia
Hyper IgE cellular causes
IgE elevation is just a marker for disease
true cause is from problem with neutrophils and T cells
Primary Immunodeficiencies with Onset of birth to 3 months
phagocytic cell defects, complement defects, Digeorges
Primary Immunodeficiencies with Onset of 3-6 months
SCID
Primary Immunodeficiencies with Onset of 6 to 18 months
X linked agammaglobulinemia and transient hypogammaglobulinemia
Primary Immunodeficiencies with Onset of 18 months to adult
common variable immunodeficiency and complement defects
treatments for humoral antibody deficiency
prophylactic antibiotics
IVIG and SQIgG
treatments for combined immunodeficiency
stem cell IVIG prophylactics enzymes for PEG-ADA gene therapy Thymic transplant in digeorges
treatments for phagocytic cell defects
prophylactic antibiotics, avoid live viral vaccines (hyperIgE), gamma interferon in CGD, bone marrow
kawasaki disease presentation
conjuctivitis, swollen lymph nodes, swollen hands/feet, rash, changes in oral mucosa
4/5 means kawasaki, IVIG and aspirin
can lead to vasculitis and increased risk of coronary artery disease
should you give vaccine when on steroids?
maybe not because the steroids tone down CMI mainly and can cause the vaccine to not be as effective
