Primary Immunodeficiencies Flashcards
Most common immunodeficiency
HIV
How are PIDDs classified
Based on the component of the immune system that is involved
Adaptive immune defects
- antibody syndromes
- combined immunodeficiencies
Innate immunity defects
- disorders of phagocytes
- TLRs
- complement
must be wary of Primary immunodisorder if recurrent infections/unusual infections occur
Severe combined immunodeficiency (SCID)
Most severe form of antibody deficency (adaptive)
Virtually lack functional T-cells
- some B/NK cell deficency may also occur
Clinical features
- diarrhea
- pneumonia
- rashes
Adenosine detainees deficiency (ADA)
Type of SCID that affects T and B cell maturation
- cells dont have ADA (Adenosine deaminase) so cant convert adenosine to inosine which is required for maturation of B and T cells
- is also a housekeeping enzyme so found in all cells and possess a very wide grouping of symptoms*
- autosomal recessive and 10-15% of SCID diagnosis
Primary Symptoms:
- deafness
- behavior issues
- liver toxicity
X-linked SCID w/ common gamma chain defect
Defective IL2RG gene that disables cytokine receptors in IL-2,4,7,9,15,21 in immature T cells and NK cells
- causes improper NK development (IL-15) and T cell development (IL-7)
X-linked disorder, accounts for 40% SCID diagnosis
MOST COMMON SCID
Use flow cytometry to determine levels of gamma chains
Recombinant-activating gene 1 and 2 (RAG1/RAG2)
Genes RAG1/2 are defective and disables DNA cleavage required during recombination for pre-T cell and Pre-B cell receptors
Affects only T and B cells, NK cells are normal
Autosomal recessive SCID accounting fro 20% of SICD diagnosis
Hyper IgM syndrome (CD40 ligand deficiency)
Produces a deficiency of CD40L which is required by CD T lymphocytes to interact with B cells and dendritic cells
Cannot class switch from IgM and also prevents dendritic maturation and IL-12 secretion (poor innate immunize system)
X-linked and is very rare
X-linked (burtons) agammaglobulinemia
Defect in signaling through pre-BCR via BTK deficiencies
Prevents pro-B -> pre-B stages and leaves to super low B-cell levels
- low/no antibodies
Use flow cytometry and check for BTK levels
No tonsils will be present in young patients is cardinal symptom
MOST COMMON agammaglobulinemia
Common variable immunodeficiency (CVID)
most common clinically significant immunodeficiency
Reduced levels of one or more isotopes AND impaired B cell/antibody function
- normal Bcell levels are present
Marked by recurrent infections of respiratory tract and can increases chances of granulomas, lymphoid cancers and autoimmune diseases
Most common defect associated with CIVD is TACI defects
- expressed by B-cells and is responsible with for activating B cells via APRIL factor
IgA deficiency
Most common antibody deficiency
Often asymptomatic but does experience recurrent mucosal infections and autoimmunity
Most commonly diagnosed during pneumococci infections (patient cant beat them)
Phagocytic cell defect types
Inadequate numbers = Neutropenia
Defect in phagocytic function =chronic granulomatous disease (CGD)
Impaired trafficking = leukocyte adhesion deficency (LAD)
Types of neutropenia
Severe congenital neutropenia = stupid low levels (<500/ml) and is
autosomal dominant
Cyclic neutropenia = normal levels of neutrophils but die way quicker
- marked by recurrent infections every 3 weeks
Both are caused by deficiencies in the elastase gene (ELA2)
Chronic granulomatous disease
Defects in nicotinamide adenine dinucleotide phosphate (NADPH) in phagosomes
- 75% X-linked (worse)/ 25% Autosomal recessive (better)
Reduces overall killing ability of phagosomes
- no respiratory burst
Marked by unusual infections often in lungs and sustained inflammatory responses
(examples are aspergillosis, mycobacteria and nocardia infections)
Leukocyte adhesion deficiency (LAD)
Multiple forms
- LAD1: defect in B2-integrins (CD18) which mediates adhesion in extraversion between leukocytes and ICAM in endothelial cells
- LAD2: defect in Sialyl-Lewis-X on leukocytes impairs selectin up regulation (cant roll to stabilize integrin activation
- marked by poor wound healing, no pus formation, periodontitis and delayed separation of umbilical cord*
Use flow cytometry to diagnosis
defects in Toll-like receptors (TLRs)
usually result from MyD88 and IRAK defects
- results in the inability of the cell to recognize PAMPs and realize it is infected
Autosomal recessive and present with pyogenic infections early in life
Monitor IL6 and TNF alpha levels with TLR agonists to diagnosis
