Immunodeficiency and HIV Flashcards
(34 cards)
What can the immune system be divided into?
Innate- the one that we are born with & our first response (e.g. phagocytes, complement, etc.)
Adaptive/acquired- changes throughout life (e.g. T cells, B cells, etc.)
What does immunodeficiency result in & what is an indication of immunodeficiency?
Immunodeficiency results in increased susceptibility to infection by specific classes or types of microbes.
Repeated or unusual infections is an indication of immunodeficiency
What is primary & secondary immunodeficiency?
Primary immunodeficiency:
Genetically determined or result of developmental anomalies
Inherited, congenital, and rare
Secondary immunodeficiency:
Acquired & caused by disease or an immunosuppressive treatment
More common
What can primary immunodeficiencies be a result of?
it can be genetic so:
autosomal,
X-linked (sex chromosome),
gene deletions, rearrangements, polymorphisms (SNPs).
Or it can be biochemical or metabolic so:
adenosine deaminase deficiency (affects T cells), purine nucleoside phosphorylase deficiency (affects T cells),
developmental arrest (affects B cells, T cells, phagocytes)
What are some examples of complement deficiencies that affect the classical pathway?
Defects that affect the classical pathway (C1qrs, C2 or C4) lead to:
Immune complex disease unable to remove Ag-Ab complexes (Type III hyper.)
Susceptibility to encapsulated organisms such as Streptococcus pneumoniae and Neisseria spp
What are some examples of complement deficiencies such as C3 deficiency?
Opsonisation of microbes is defective hence:
removal by phagocytosis is compromised
susceptibility to encapsulated organisms i.e. Streptococcus, Neisseria, pyogenic organisms
What are some examples of complement deficiencies such as Alternative pathway deficiencies (Factor B, Factor D and Properdin)?
Results in low C3b levels:
pneumococcal and meningococcal infections
no immune complex disease
What are some examples of complement deficiencies such as MAC complex deficiency (C5-9)?
Inability to lyse bacterial cells hence:
recurrent infection with Neisseria meningitidis
humoral (antibody) immunity is unaffected
Phagocytosis deficiencies - what are the consquences when there are defects in the stem cell differentiation?
Neutropaenia (low neutrophil numbers) Leukocyte adhesion disease - lack of adhesion molecules (CD18, that binds to ICAM-1) required for Neutrophil recruitment
Phagocytosis deficiencies - what are the consquences when there are defects in phagocytosis?
Also known as Chediak-Higashi syndrome.
Lack of phagosome fusion with lysosomes:
-defect in lysosomal trafficking regulator (LYST)
-susceptibility to staphylococcus aureus
Phagocytosis deficiencies - what are the consquences when there are defects in Defective intracellular Killing?
Also know as Chronic granulomatous Disease.
Defect in NADPH system:
-required for free radical formation (ROS)
-lack of oxygen-dependent killing
-increased bacterial and fungal infections
What can phagocytosis deficiencies all lead to?
General increased susceptibility to bacterial and fungal infections of skin and mucosal tissues
What is the treatment for Phagocytosis deficiencies?
Treatment: antibiotics or bone marrow transplant (gene therapy)
Humoral / antibody deficiencies - what are the consequences of abnormal b cell development?
Abnormal b cell development can lead to Bruton’s agammaglobulinaemia (x-linked agammaglobulinaemia).
Few or no mature B cells / antibody leads to:
-Blockage in maturation of pre-B to B cells, while T cell maturation is normal
-Common in male infants; protected for 6-months, then recurrent bacterial infections
Humoral / antibody deficiencies - what are the consequences of Failure of class switch from IgM?
Increased igM but little or no IgG
- Lack of igG antibody opsonization and phagocytosis (ex,defective CD40 on B cells or CD40L on T cells)
Humoral / antibody deficiencies - what are the consequences Common variable immunodeficiency?
many potential causes but not completely known
IgG/IgM/IgA deficiency:
- either B cells do not undergo terminal differentiation (no IgG/IgA) or T cell signalling is defective
- adults of box sexes (late onset, 15-35 yrs)
what can Humoral / antibody deficiencies lead to?
Recurrent extracellular bacterial infections (Pneumococcus, Streptococcus, Haemophilus, mainly encapsulated bacteria)
What is the treatment for Humoral / antibody deficiencies?
Treatment: life-long or periodic gamma globulin injections
T cell deficiencies - what are the consequences of undeveloped thymus?
Also known as DiGeorge’s syndrome.
Lack of T cells:
- susceptibility to many infections, abnormal B cell immunity
- hypoparathyroidism (resulting in hypocalcemia and congenital heart disease)
T cell deficiencies - what are the consequences of Stem cell defect or death of developing T cells?
Severe combined deficiency syndrome (SCID):
- Defect in the common gamma chain used by cytokine receptors (IL2/4/7/9/15/21) in 50% of cases
- Adenosine deaminase deficiency or purine nucleoside phosphorylase deficiency in 25% of cases (metabolite build up inhibiting DNA synthesis)
T cell deficiencies - what are the consequences of MHC II deficiency?
No mature CD4+ T cells:
- Low antigen presenting cell function, reduced B/T cell activation (no antibodies)
- Death by yr 5 due to bacterial and viral infections
What can T cell deficiencies lead to?
Opportunistic infections (viruses, fungi, parasites, bacteria). Often fatal in early years of life.
What is the treatment for T cell deficiencies?
Treatment: bone marrow transplant (gene therapy)
What are some clinical features of immunodeficiencies?
- Chronic and recurrent infections
- Unusual microbial agents
- Incomplete responses to treatment
- Skin lesions, warts
- Diarrhoea
- Recurrent abscesses
- Autoimmunity
- Failure to thrive
