Lec 2 - primary immunodeficiency Flashcards
Define primary and secondary immune deficiency
Explain the classification of primary immune deficiency disorders.
Give examples of primary disorders of T cell, B cell, phagocyte and complement function.
Understand the causes of primary immunodeficiency
Illustrate the complications of immune deficiency disorders
List the clinical features of primary immunodeficiency
Understand the principles of the treatment of primary immunodeficiency
.
Are babies born with immunoglobulins present in their blood
Yes - maternal IgG transferred but NO PRODUCTION OF OWN ANTIBODIES YET
Primary immunodeficiency
- define
- causes
- predisposition to
Congenital defect in one or more components of the immune system
Causes
- Mutations (MAJORITY) –> either missing or abnormally functioning part of immune system
- Autoimmunity
Infections + tumours
Secondary immunodeficiency =
Acquired defect in one or more components of the immune system
Major consequence of immunodeficiency
Increased risk of INFECTION
Abnormalities of primary immunodeficiency can arise from 3 places
Components of the innate immune system
Stages of lymphocyte development
Responses of mature lymphocytes to antigenic stimulation
OR
Simpler classification
- phagocyte defects
- complement defects
- defects of other innate components
Examples of primary disorders of PHAGOCYTE function (3)
Chronic granulomatous disease
Leukocyte adhesion deficiency
Myeloperoxidase deficiency
Examples of primary disorders of COMPLEMENT function (3)
Complement deficiencies
Hereditary angioedema
Examples of primary disorders of T CELL function
DiGeorge syndrome
Chronic mucocutaneous candidiasis
Examples of primary disorders of B CELL function
.
B cell/antibody deficiency makes you susceptible to bacterial or viral infection more?
Bacterial, e.g. otitis, pneumonia, meningitis, osteomyelitis
T cell deficiency makes you susceptible to what pathogen mostly + which others?
Viral (MOST), e.g. CMV, reactivation of HSV, VZV
Protozoa, e.g. pneumocystis
Fungal, e.g. candida
Atypical mycobacteria
Repeated infection with encapsulated bacteria is a sign of defective production of what
Antibodies
Phagocyte defects make you susceptible to what type of infection more
Fungal
Severity of T cell immunodeficiency can be reflected in pattens of infection by what pathogen
Mycobacteria (an atypical bacteria)
T cell immunodeficiency can activate viruses which induce tumours
Give some examples
Human herpesvirus 8 (HHV8) - kaposi’s sarcoma
EBV - non-hodgkin lymphoma
3 broad causes of primary immunodeficiency
Mutations
-altered DNA sequence of a gene
Polymorphisms
- more than one allele of a gene
- very mild effect
Polygenic disorders
- i.e. more than one gene causing disease
- COMMON
Classification of primary immunodeficiency disorders (4)
1) Severe Combined Immune Deficiency (SCID)
2) Predominantly antibody deficiencies
3) Predominantly T cell deficiencies
4) Other (usually combined T & B) deficiencies
What is SCID (SEVERE COMBINED IMMUNE DEFICIENCY)
A group of disorders that affect both T and B cells (VERY LOW LYMPHOCYTES –> deficiency in cellular and humoral immunity)
Infants with SCID die before age of 2 unless treated with what
Stem cell transplant
-can cure it but MUST BE GIVEN ASAP (i.e. within weeks of birth)
Cause of SCID
Mutations leading to defects in pluripotent stem cells, lymphoid stem cells or T & B cells themselves
Polymorphisms can occur in a gene which codes for MHC
Name this gene
HLA
Examples of polygenic primary immunodeficiency disorders
IgA deficiency
Common variable immunodeficiency - commonest one requiring treatment
Specific antibody deficiency
Some primary immunodefiencies are caused by autoimmunity
Name one
Autoimmune polyendocrinopathy candidiasis ectodermal dysplasia (APECED)
Complications of immune deficiency disorders
INFECTION
Other presentations
- malignancy
- immune dysregulation (–> autoimmunity, hypersensitivity etc)
- general unexplained features, e.g. failure to thrive, large spleen
Chronic tissue/ organ damage (arising from inflammation +/- delays in diagnosis/treatment)
Iatrogenic complications associated with the use of potent immune modulating therapies
Clinical features of primary immunodeficiency
Recurrent INFECTION
-e.g. pneumonia, osteomyelitis, skin/mucous membrane infection, neisserial, bronchitis
Immune complex disease
Organ damage
Blood disorders
Delayed growth + development
Autoimmune disease
Clinical features of SCID
Recurrent/severe/opportunistic infections Failure to thrive Diarrhoea Diffuse rash Absent thymus
Clinical presentation of antibody deficiency
Most present later in life
Recurrent bacterial infections of resp tract
Principles of the treatment of primary immunodeficiency
PREVENT INFECTION
- prophylactic antibiotics
- Ig replacement if severe deficiency
Treat underlying cause
Avoid live vaccines
Avoid blood transfusion in cell mediated immune defects
Genetic counselling
Specific therapies
- stem cell transplant
- Ig replacement
- gene therapy
- cytokine therapy
Are primary or secondary immunodeficiency disorders more common?
Secondary
Causes of secondary immunodeficiency disorders
Malnutrition Malignancy Immunosuppressive therapy Splenectomy Chronic renal failure Severe burns/surgery
