Immunodeficiencies Flashcards
Primary Immunodeficiencies
Result from intrinsic defects in cells and/or organs of the immune system.
Generally due to genetic defects.
Children to Adult ratio 3:2
Male to female ratio 5:1
Secondary Immunodeficiencies
Result from extrinsic factors such as malnourishment, disease, malignancy, medical treatment, or environmental exposure.
The more common type of immunodeficiency.
Recurrent Infections
with
Encapsulated Extracellular Bacteria
Suggestive of deficiency in:
Immunoglobulin / B-cells
Complement
Phagocytic cells
Examples:
superficial skin infections
ear infections
septicemia
Some are also susceptible to some viruses and certain intestinal parasites.
Recurrent Infections
with
Intracellular Pathogens
Suggestive of T-cell deficiencies.
Typically suffer from infctions with microorganisms that normal individuals rapidly develop resistance against.
Examples:
Viruses
Mycobacteria
Fungal
Protozoan pathogen
Candida
Pneumocystis
B-cell Immunity
Testing
-
Quantification
- B-cells
- Flow cytometry
- CD19+
- CD20+
- CD21+
- Flow cytometry
- Ig levels (total, classes, and subclasses)
- ELISA
- RIA
- radial immunodiffusion
- B-cells
-
Function
- Immunize patient with protein or carbodydrate antigen
- Quantitate Ab levels 2-4 weeks later
- Compare titers of different Ig classes
T-cell Immunity
Testing
-
Quantification
- Flow cytometry
- CD3+ = all mature T-cells in peripheral blood
- CD4+ = helper T-cells
- CD8+ = cytotoxic T-cells
- CD25+ (α-subunit of IL-2R) = activated T-cells
- Flow cytometry
-
Function
- In vivo
- DTH testing using panel of Ag which patient has been immunized to in the past
- Positive type IV hypersensitivity reaction at site of injection 48-72 hours later suggestive of proper function
- In vitro
- Mitogen or specific antigen-induced proliferation
- Mixed lymphocyte reaction
- In vivo
X-linked Aggamaglobulinemia
(XLA)
- Defect in Bruton’s tyrosine kinase (Btk)
- X-linked
- Inability to differentiate from pre-B cell into immature B cell
- See complete absence of B-cells and Ab
-
High frequency of:
- Upper and lower respiratory tract infections
- Bacterial meningitis
- Septicemia
- Treat with IV-Ig & antibody prophylaxis
- Males usually die by 4th decade due to obstructive lung disease secondary to recurrent URIs
Agammaglobulinemia
Secondary to mutated μ heavy chain gene
- Defect in μ heavy chain gene
- Inability to mature from pro-B cell to pre-B cell
- See complete absence B-cells and Ab
Hyper IgM Syndrome
(HIGM)
- Mutation or deletion of the CD40-ligand gene
- Defect in T-cells
- Most forms X-linked, some rare AR types
- Inability to induce isotype switching
- Effect exhibited in B-cells
- See elevated (10x) levels of IgM in adults
- [IgM] can appear normal in children
- Treat with pure IV-IgG without IgA to prevent type III hypersensitivities & prophylatic abx
Transient Hypogammaglobulinemia of Infancy
- Onset of normal IgG synthesis delayed as much as 36 months
- Infant initally protected by materal IgG
- Daly of endogenous Ig synthesis makes them every susceptible to infections
- Treat with supplemental IV-IG until issue resolves
Selective IgA Deficiency
- See dramatically decreased levels of IgA
- Normal levels of IgM and IgG
- Normal B cell and plasma cell numbers
- Unknown etiology
- Most common primary immunodeficiency in the USA
- See increased sinopulmonary infections
- DO NOT have significantly increased susceptibility to recurrent infections
- Make anti-IgA antibodies → can see anaphylaxis following plasma transfusion
IgG Subclass Deficiencies
- Abnormalities in one or more subclasses of IgG
- Normal B cell and plasma cell numbers
- Varied immune defects based on effected class
- Can go undetected
- May see absent IgG levels in infant d/t failure of placental transfer
Common Variable Immunodeficiency
(CVID)
- Heterlogous group of disorders with reduced serum Ig levels
- Peripheral T cell and B cell levels normal
- Develops during second or later decade
- Cause unknown
DiGeorge Syndrome
(Congenital Thymic Aplasia)
- Small, absent, or “misplaced” thymus
- Low or absent T-cell population and function
- Increased susceptibility to intracellular pathogens which generally improves with age
- Likely due to extrathymic T-cell maturation
- B cell function variable
- serum IgG levels often normal
- Also see:
- congenital heart disease
- hypoparathyroidism
- abnormal facial structures
Chronic Mucocutaneous Candidiasis
- Severe, chronic superficial infections with Candida albicans
- Likely due to a selective defect in T-cell function
- Other T & B cell mediated defenses appear normal