Immunodeficiency Flashcards
Primary vs secondary
Primary (congenital)
- recognize repeated infections (resp, skin, fungal), family history, failure to thrive
Secondary (acquired) - more common
- cancer, irradiation, chemo, malnutrition
Evaluation of immunodeficiency
Generally divide into four distinct categories
- antibody-mediated
- cell-mediated
- usu leads to intracellular pathogens (viral, mycobacterium)
- phagocyte function
- complement
Evaluation of antibody immunity
Serum Ig levels
- detect specific antibodies (inc after vaccine)
Detect circulating B cells (inc with mAb’s to BCR)
Induce B-cell differentiation
Lymph node biopsy
Evaluation of cell-mediated immunity
Test delayed hypersensitivity (candida, streptokinase) Total lymphocyte count (60-80% are T) Differentiate with CD3, CD4, CD8 Test reaction to lectins, alloantigens Test IFN-g, IL2, etc
Evaluation of phagocyte function
Granulocyte and monocyte count Chemotaxis assay Test phagocytosis of opsonized particles Test for superoxides Levels of enzymes, IL1, IL12 Response to IFN-g, GM-CSF
Evaluation of complement system
Complement assays (CH50 = total hemolytic, individual components) Neutrophil chemotaxis assay
Antibody/B-cell deficiencies
B cell maturation or antibody production
-> recurrent bacterial infections (pneumococcus, strep, hemophilus)
Brutons/XLA - defective btk -> don’t activate pre-B -> immature B
Hyper IgM - no CD40 or CD40L -> can’t switch antibody
CVID (common variable) - B cell or Th cell
- low IgG - low vaccine response, lymphoma, autoimmune -> tx with IV IG
- low IgA - most common -> URI, GI
Transient hypogammaglobulinemia of infancy - low CD4 activation -> resolves by age 4
T cell deficiencies
Usually also affect antibodies
Often -> viral, funcal, mycobacterial, protozoan
DiGeorge Syndrome - small thymus (-> transplant)
Bare lymphocyte - low MHC class II -> no CD4 -> SCID phenotype
TAP 1 or TAP 2 genes -> low MHC class I -> low CD8 (-> viral)
Wiskott-Aldrish syndrome - WAS protein -necessary for signaling/activation pathways
Ataxia-telangiectasa - ATM protein - DNA damage checkpoint -> impaired development
SCID
severe combined immunodeficiency - both B and T cell
Stem cell defects - ex common cytokine gamma chain needed for receptors (IL-2, 4, 7, 9, 15, 21) Toxicity in lymphocytes (adenosine deaminase, purine nucleoside phosphorylase) DNA recombinationo (ex RAG1, 2 -> no BCR or TCR)
Phagocytic deficiencies
Intrinsic (phagocyte differentiation, chemoattraction, intracellular killing)
Extrinsic (low activating via antibody or complement or suppression via corticoids)
Cyclic neutropenia - low count for 3-6 d per month
Leukkocyte adhesion deficiency - LAD1 (no LFA11-> integrin), LAD 2 (no E selectin)
Chediak-Higashi syndrome - phagosomes don’t fuse with lysosomes
Chronic granulomatous disease - NADPH oxidase -> can’t kill catalase+ bacteria
Defects in IFN-g (receptor or “Job’s syndrome”), IL-12, etc
Complement deficiencies
Susceptible to encapsulated (require opsonization) - pneumo, strep, Neisseria
Hereditary angioedema - C1q inhibitor -> constant activation
Paroxysmal nocturnal hemoglobulinuria - lack of “decay accelerating factor” -> lysis of RBCs
Immune complex disease - C1, C2, C4 deficiency (can remove complexes)
C3 deficiency - most serious, pyogenic bact
(similar phenotype from Factors H, I - can’t recycle C3)
MAC (C5-9) -> Neisseria
Secondary immunodeficiencies
By far most common!
HIV/AIDS -> CD4 and chemokine receptors (gp120 binding), infect monocytes and APCs -> opportunistic infections
Senescence - mostly T - thymus function, fewer activations, decrease in memory cells, less stimulation
- some antibody changes - more auto vs foreign, IgG -> IgM, lower affinity, less diversity
Immunodeficiency treatments
Antibiotics!
Antibodies - IVIg for humoral
IFN-g for humoral (ex CGD)
BMT - has been used for CGD, SCID - dangerous!
Fetal liver, thymus grafts
Gene therapies - replace faulty gene in stem cells
Avoid live vaccines (MMR, polio)
Education, genetic counseling, prenatal testing
