Immunodeficiency Flashcards
Primary immunodeficiency
Intrinsic genetic defects in immune system
Affects T & B cells (Ab production), complement,
phagocytes
Absence or failure of NORMAL function in one or more elements of immune system
Immunodeficiency causes > susceptibility
to infection in individuals
-specific or non-specific
Secondary immodeficiency
External factors that can deleteriously affect immune system
Drugs (hormones, cancer therapy, transplants), Malnutrition, Viral infection, burns
Primary immunodeficiency: specific immunodefiency
Abnormalities of T or B cells - Adaptive Immune System
Primary immunodeficiency: non-specific immunodefiency
Abnormalities of phagocytes or complement - innate immune system
People with immunodeficiencies fall into 2 categories:
- Defects in Ig, C’, phagocytes – susceptible to recurrent
bacterial infections (H. Influenzae, S. Pneumoniae, S.
Aureus)
-termed: Pyogenic Infections – pus formation - Defects in cell‐mediated immunity (T cells)
-susceptible to commensal organisms (eg. Candida Candida, Viruses)
-termed: Opportunistic Infections
B-cell deficiencies
Have defects in B cell function - pyogenic infections
- X-linked Agammaglobulinemia (X-LA)
- IgA deficiency
- Hyper-IgM Immunodeficiency
X-linked Agammaglobulinemia (X-LA)
B-cell deficiency
Like many immunodeficiencies - gene affected on X chromosome (affects males)
Have no B-cells, no tonsils, little IgG in serum (but have other Igs)
X-linked recessive inheritance
Occurs more frequently in males because only have one X chromosome. Females must receive copy of defective gene from BOTH parents to have recessive disease. Females are CARRIERS if they have one copy of defective gene. The other normal gene is dominant (ie. it works) X‐linked recessive genes passed from female carriers to their ill sons and carrier daughters. Ill males would have to father a daughter to pass on gene. Unlikely because genetic diseases often cause death in childhood.
X-linked dominant inheritance
Less common than X‐linked recessive
Dominant Gene carried on the X‐
chromosome and only ONE copy of
gene is sufficient to cause the disorder.
(ie. Defective gene is dominant)
Mother has mutated gene and passes it onto her offspring
50% of children (25% male, 25% female)
will have the disease
50% will be unaffected
The sons of man with X-linked dominant disorder will not be affected, but his daughters will all inherit condition
X-linked Agammaglobulinemia (X-LA) mechanism
Defective btk gene that encodes a B cell tyrosine kinase
btk Important in maturation of B cells
No B cell maturation SO no IgG – poor Ab responses
First 6‐12 months of life have protective maternal IgG
Get recurrent pyogenic infections
X-linked Agammaglobulinemia (X-LA) therapy
Repeated injections of gamma-globulin throughout life
Hyper-IgM Immunodeficiency
Deficient in IgG and IgA but hyper IgM (large amounts of IgM)
X‐linked recessive recessive condition condition with mutations mutations in CD40
Hyper-IgM Immunodeficiency mechanism
CD40 important for ‘class switching’ Where IgM turns to IgG (Ab has same specificity) So can not switch from IgM to IgG Susceptible to pyogenic infections & autoimmune disease (form auto‐IgM antibodies to neutrophils & platelets)
IgA deficiency
Most common immunodeficiency (1 in 700 Caucasians)
Failure in terminal differentiation of B cells to plasma cells
Individuals develop Type III hypersensitivity (immune complex)
Susceptible to pyogenic infections
T cell deficiencies
Opportunistic infections
- severe combined immunodeficiencies (SCID)
- DiGeorge Syndrome
- MHC II deficiency
severe combined immunodeficiencies (SCID)
Individuals with no or poor T cell function
BUT ‐ B cell function depends on T cell function
SO ‐ T cell deficient individuals have poor T cell and
humoral functions
People with SCID suffer from
commensal organism infections
eg. Oral Candidiasis due to
Candida albicans infection
SCID in the population
SCID have very few lymphocytes
SCID more common in males‐ 50% cases X‐linked (due to
defective IL‐2R gene)
But also other genetic abnormalities that are not X‐linked
SCID is incompatible with life and infants die within first 2
years of life without bone marrow transplantation
Bone marrow transplantation – usually sibling or parental
transplantation to avoid graft rejection
DiGeorge Syndrome
T cell deficiency because of affected thymus in foetal development
DiGeorge distinctive features
Facial features:
- Wide-spread eyes
- Low set ears
- Upper lip shortened
- Abnormal aorta - also have CV disorder
MHC II deficiency
Deficiency in MHCII leads to failure express MHC II antigens on APC
Because CD4+ cells require MHCII for positive selection in the thymus, Infants deficient in MHC II
have no CD4+ cells
Lack of CD4 cells leads to deficiency in Ab
Complement deficiencies
Deficiencies in C3, Factor H and Factor I – > susceptibility to pyogenic infections
Deficiencies in MAC > in susceptibility to
Neisseria infections (N. meningitides, N. gonorrhoeae)
Most common is:
Hereditary Angioneurotic Edema (HAE)
Hereditary Angioneurotic Edema (HAE)
Most important C’ deficiency
C1 inhibitor‐ inhibits activation of C1 ( first initiator of C’
pathway)
Inhibits C’ and elements of the kinin/clotting system
Allows severe oedema due to plasma leakage leakage
Patients have recurrent swelling
Intestine - abdominal pains and vomiting
Upper airways - choke and death due to obstruction
Defects in phagocytes
Can affect Neutrophils or Macrophages
Severe depletion in neutrophils (neutropenia) results in severe pyogenic infections
2 genetic defects defects that are often fatal:
1. Chronic Granulomatous Disease (CGD)
2. Leukocyte Adhesion Deficiency (LAD)
Chronic Granulomatous Disease (CGD)
Defective NAPDH oxidase
Phagocytes CANNOT form superoxide ions & H2O2 (ROS‐ Reactive
Oxygen Species) to kill microbes
Organisms remain alive in phagocytes – persistent intracellular infections &
granulomas form
Infections with S. Pneumoniae &
abbesses in liver, skin etc.
