Immunodeficiency Flashcards
What are the 2 ways you can acquire and immune deficiency
- Congenital - primary (genetic)
- Acquired - Secondary (disease or therapy)
What is the most common cause of secondary immunodeficiency worldwide
Malnutrition
What are the 4 classifications of primary immunodeficiencies
- T cells
- B cells
- T and B cells
- Phagocytes
- Complement
What percentage of males affected by primary immunodeficiency
70&
What % of PI affect B cells
50%
What % of PI affect T cells only
10%
What are the 3 basis of PID
Mutation
Polymorphisms
Polygenic disorder - most common
What are common consequences of PID
Opportunistic infection
A patient with PID affected by an opportunistic virus is likely due to what defect
T cell
A patient with PID affected by an opportunistic bacteria is likely due to what defect
B cells, phagocytes and or complement
What is SCID
Severe combined immunodeficiency
Most common mutation resulting in SCID
IL2RG (interleukin receptor) - 19% of cases
What is functioning in SCID
Complement and phagocytosis
What are treatment and maintence of SCID
Maintenance:-Bactrim, Azithroprine -IgRT
Treatment: - Replacement therapy (e.g. ADA injections) - BMT - Gene Therapy (only if you know the gene)
How does do George syndrome develop
Microdeletion of 22q
Why do people with do George’s syndrome get hypo-calcaemic seizures?
no parathyroid gland
What genetic defect creates ataxia-telangiectasia
Autosomal recessive, chromosome 11
What is treatment of ataxia-telangiectasia
No cure, slow neurodegeneration (antioxidants)
What mutation results in wisdom-Aldrich disease
WASP gene of Xp11 - X linked recessive
What is a treatment of Wiscott-Aldrich disease
Bone marrow transplant can cure
What is Brutons X linked Agammagloulinemia
Absence or deficiency of a Bruton’s tyrosine kinase: maturation arrest
of pre-B cells
What is the treatment of Brutons
immunotherapy - IgRT
CVID is the most common ID. What percentage of genes have been identified
Only 10%
How does it cause deficiency
Low IL-2, IFN-g, CD40L (defective CD4 function )
Treatment for CVID?
immunoglobulin replacement therapy
IgRT to keep IgG >400
What is the clinical presentation of selective IgA deficiency
Most are clinically normal but with very low IgA
What is treatment for IgA deficiency
Just treat problems do not give immunotherapy
Examples of PID affecting phagocytes and complement
Complement deficiencies
Paroxysmal nocturnal hemoglobinuria (PNH)
Hereditary angioedema
Chronic granulomatous disease (CGD) * Myeloperoxidase deficiency
Glucose-6-phosphate dehydrogenase deficiency
Leukocyte adhesion deficiency
Chediak-Higashi syndrome
Autoinflammatory disorders
How does cheddar-Higashi syndrome cause pathology
The lysosomes fail to fuse with the phagosome
Neutropenia + diminished chemotaxis + Decreased (slower) neutrophils, NK cell and CTL functions.
* The platelets are abnormal (easy bruising). Pyogenic infections. * Oculocutaneous albinism, photophobia, enterocolitis and peripheral neuropathy.
* 85% of children with CHS develop fatal lymphoma-like condition.
giant lysosomes
What is the treatment for cheddar-Higgs hi syndrome
Bone marrow therapy/transplant
How many types of LAD is there?
Leukocyte adhesion deficiency
3
LADI- lack of CD18 β-2 – lack CR3 & unable to respond to C3b opsonin
LADII – defective GDP-fucose transporter & inability to fucosylate sialyl LewisX structures
LADIII - mutation of integrin-activating molecule kindlin 3
What infectious disease is associated with Leukocyte adhesion deficiency LAD
Widespread pyogenic bacterial infections
What mutation produces PNH paroxysmal nocturnal haemoglobinuria
PIG - A gene
results in inability to synthesise glycosyl phosphatidylinositol (GPI) anchors
What does PNH impact on
RBC
Lack of GPI-anchored complement control
proteins CD55 and CD59 on erythrocytes Erythrocytes susceptible to complement-
mediated lysis
What does a Neisseria infection suggest?
complement defect
What does candida infection suggest
Phagocyte or T cell deficiency (mainly phagocyte)
What does pneumonitis, TB, HHV8, EBV, CMV suggest
T cell deficency
What are medical history warning signs for PID
> 8 ear infections / year
2 serious sinusitis / year
2 pneumonias / year
2 deep-seated infections, or
infections in unusual areas
Recurrent deep skin/organ abscesses
Need for IV ABx to clear infection
Infections with unusual /opportunistic
organisms
Family Hx of PID
What physical signs would you see suggesting PID
Poor growth, FTT
Absent lymph nodes or tonsils
Skin lesions: telangiectasias,
petechiae, lupus-like rash
Ataxia, ocular lesions
Oral thrush after 1 year of age
Oral ulcers
When is IgRT most beneficial
Primary immune defects with no B cells, with hypogammaglobulinemia and impaired specific antibody production
What is the mechanics of action of immunoglobulin replacement therapy (IgRT)
IC formation
Antinflammatiory DC
Complement activation
Phagocytosis
T cell activation
What diseases use bone marrow transplantation as treatment
Hyper-IgE syndrome produce the best outcome
SCID
Wiscott-Aldrich
Chediak-Higashi
Kostmann Disease
How many PID are there
Approx. 300
Give some examples of secondary immunodeficiency causes
Environment and stress
HIV and infection
Malnutrition
Immunosuppressive drugs
Surgery and trauma
Age (premature and very old)
Give examples of infections which can cause immunodeficency
HIV, CMV, EBV, toxoplasma
How does HIV cause defficiency
Reduces T cells (specifically CD4 T cells)
What cells are affected by HIV
CD4 T cells, macrophages, monocytes
What is the treatment for HIV
HAART
By the age of 70-80 what happens to the thymus
It is unable to generate any more T cells - immunocompromised
