Immunodeficiency Flashcards
The difference between primary and secondary immunodeficiencies Examples of Primary Immunodeficiency Examples of Secondary Immunodeficiency (34 cards)
Primary immunodeficiency
What does it affect
Intrinsic genetic defects in immune system
T&B cells (Ab production), complement cascade, phagocytes
Secondary immunodeficiency
Caused by?
External factors which can deleteriously affect the immune system
Drugs, malnutrition, viral infection
Primary immunodeficiency (Detail)
What does it cause
Two types
Absence or failure of normal fx in one or more elements of immune system
Increased susceptibility to infection
Specific/Non-specific
Specific immunodeficiency
Abnormalities of T or B cells - adaptive immune system
Non-specific immunodeficiency
Abnormalities of phagocytes or complement - innate immune system
Two categories of primary ID and what are they at risk of
- defects in Ig, Completment, phagocytes –> recurrent bacterial infections
PYOGENIC - defects in cell-mediated immunity (T cells)
Infection by commensal organisms
OPPORTUNISTIC infections
B cell deficiencies
Increase in
Defects in B cell fx
Pyogenic infections
X-linked Agammaglobulinaemia
Which gene is affected therefore who does it affect
Signs and symptoms
First ID discovered
Gene on X-chromosome
Affects males
No B-cells
No tonsils
Little IgG in serum (other Igs present)
X-linked recessive inheritance
Occurs more frequently in
Females having one copy of gene =
Males because only one X chromosome
Carriers
Passed on to ill sons and carrier daughters
Ill males pass on to daughters
X linked dominant inheritance
Mechanism
Who has mutated gene
Stats
Affected man?
Less common
Dominant gene carried on X chromosome and only one copy needed to cause disorder
Mother passes on mutated genes to offspring
50% of children will have disease
Sons will not be affected if father has gene but daughters will
X linked agammaglobulinaemia
Mechanism
Results in
Symptoms
Therapy
Defective btk gene which encodes B cell tyrosine kinase
Important in B cell maturation
No B cell maturation so no IgG - poor Ab responses
Protective maternal IgG during first 6-12 months of life
Recurrent pyogenic infections - repeated injections of gamma globulin
Hyper-IgM Immunodeficiency
What kind of condition
Susceptible to…because
Deficient in IgG and IgA but HYPER IgM
X linked recessive condition with CD40 mutations
IgM turns to IgG
Susceptible to pyogenic infections and autoimmune disease due to anti IgM antibodies to neutrophils and platelets
IgA deficiency
Mechanisms
Most common
Failure in terminal diff of B cells to plasma cells
Type III hypersensitivity develops
Susceptible to pyogenic infections
T cell deficiencies result in
Opportunistic infections
Severe combined immunodeficiency
Results in
Example
SCID
Individuals with no or poor T cell fx
B cell function depends on T cell fx
T cell deficient individuals have poor humoral fx due to poor interaction
Commensal organism infections e.g oral candidiasis
Signs and symptoms of SCID
Few lymphocytes More common in males 50% cases X-linked Incompatible with life - infants die within first two years of life without bone marrow transplantation Sibling or parental
DiGeorge syndrome
Distinctive facial features
Affected thymus in foetal development –> T cell deficiency
Wide spread eyes, low set ears, upper lip shortened,abnormal aorta with CVS disease
MHC II Deficiency
Failure to express MHC II antigens on antigen presenting cells
Positive selection of CD4 cells in thymus doesn’t occur
Infants are deficient in CD4 cells therefore
CD4 cell deficiency leads to Ab deficiency
Complement deficiency
Most common
Deficiencies in C3, Factor H and I
Increased susceptibility to pyogenic infections
MAC deficiencies
Increase in susceptibility to neisseria
Hereditary angioneurotic oedema
HAO
Hereditary angioneurotic oedema
Complement deficiency
C1 inhibitor
Inhibits C1 activation (first step of cascade)
Inhibits complement cascade and elements of clotting cascade
Severe oedema due to plasma leakage
Recurrent swelling
Intestine - abdo pains and vomiting
URT - choke and death due to obstruction
Chronic granulomatous disease
Due to
What is the problem
Defective NAPDH oxidase
NADPH Oxidase
NADPH + 2O2 —-> NADP+ + 2 O2 + H+
NADPH oxidase usually catalyses reaction to produce superoxide ions
Superoxide ions are required to kill bacteria after phagocytosis
Bacteria continue to live within phagocytes
Phagocytes cannot form superoxide ions and H2O2 to kill microbes
Organisms remain alive in phagocytes - persistent intracellular infections and granulomas form
Infections with s pneumoniae and abscessed in liver and skin
Diagnosis of CGD
Inability of phagocytes to reduce nitroblue tetrazolium dye
Usually pale yellow when taken up by phagocytes during phagocytosis
In healthy phagocytes it is reduced by ROS to purple
Remains yellow in CGD patients
Leukocyte Adhesion Deficiency
Type 1
ALSO
Type 2
LAD
Deficient for CD18
Defective complement receptor 3 (for CD18)
Binds bacteria opsonised with C3bi - increase phagocytosis
Opsonised bacteria cannot be phagocytosed due to defective receptor –> lack of binding –> recurrent infections
Defective CD18
Important in leukocyte adhesion
Phagocytes cannot bind to epithelium and extravasate and enter tissues
Defective receptors CD15 which bind selections
Phagocytes cannot roll on the endothelium
Secondary immunodeficiency detailed
Occurs because
Factors
Due to external effects on immune system
Drugs (hormones, cancer, therapy, transplants)
Nutrition
Viruses
Burns
