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EM
Semmelweis University
November 28/ 2016
Increased susceptibility to infections and tumors
Primer immune defficiencies
IgG defficiency XLA
Hyper IgM syndrome
SCID: severe combined immunodeficiency
disease
Lack of T lymphocytes and adaptive immunity, (result of several gene mutations)
Chains of cytokine receptor and signalling molecules are coded by 3 genes, 5 genes are required
for development of antigene receptor (adenosine deaminase, purine salvage pathway,
phosphatase – CD45).
In human SCID developes as a result of complete deficiency of T cell antigene
receptor/CD3 complex CD3ε chain.
David Phillip Vetter (1971 – 1984) a texan
(USA) boy suffered from SCID. Majority of
his life was spent in a spacesuit like dress
providing sterile environment in Children
Hospital/ in Houston. He was known in the
media as
„the boy in the plastic bubble”
A bone marrow transplant from his sister
resulted his death when he was 13 yrs old.
SCID: severe combined immunodeficiency
disease
J Clin Invest. 2004;114(10):1409–1411.
DiGeorge syndrome
(DGS, congeniális thymus hypoplasia, III.-IV. pharyngeal arch syndrome)
22q11.2 deletion syndrome
Prevalence ~ 1:4000
It was described by the pediatric-endocrinologist
Angelo DiGeorge in 1968.
There is a wide range of symptomes.
Chief symptomes are such inborn deficiencies like
• congenital heart failure,
• closing palate disorders,
• deffects of velo-pharyngeal closing,
• learning ability disorder,
• face deformities,
• recurrent infections
X-chrs linked agammaglobulinemia (XLA, Bruton type
agammaglobulinemia, Bruton syndrome)
Deficiency of B cells and IgG in peripherial blood
• Pathogenesis: impaired differeciation and growth of pre-B lymphocytes
• Genetics: XR, males
• Clinical characteristics: recurrent bacterial infections, lack of Ab responses in
vaccination
•
Treatment: pooled gamma globulin products
Smallpox vacciation
22 months old boy - XLA
linked vaccinia necrosum.
http://www.rightdiagnosis.com/phil/html/smallpox/3328.html
Hyper-IgM Syndrome
(Ig immunodeficiency with increased levels of IgM)
Patients are unable to transform IgM to IgG, IgA and IgE.
Therefore there are decreased IgG and IgA levels with normal or increased IgM levels.
•
Pathogenesis: lack of T cell CD40L. CD40L does not bound to CD40 on the B cells 
there is no B cell stimulation to take place class switch.
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Genetics：XR, male (frequently), AR (rare)
Clinacal characteristics：recurrent pyogenic infections, increased IgM levels,
decreased IgA and IgG
Selective IgA deficiency (SIGAD) (frequent)
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Immunological characteristics: deficiency of serum IgA <50mg/L
Pathogenesis: problem with the terminal differenciation of B cells
Clinical characteristics: recurrent infections of respiratory, intestine and urogenital
system.
•
Treatments: in some cases the IgA synthesis is spontaneously recovered as a result of
breast feeding.
Chronic granulomatosis (CGD)
Immunology
Pathogenesis：
decreased number and impaired function of phagocytes
NADH/NADPH oxidase deficiency in neutrophils
Decreased bactericid ability based on oxygen is a diverse genetic
deficiency where the synthesis of reactive oxygen radicals for killing
intracellular pathogens is decreased in immunecompetent cells.
(most frequently the sureoxide synthesis is disturbed).
The deficiency leads to formation of granulomas in different organs.
Prevalence in USA 1:200,000.
Chronic Granulomatous Disease-Causes-Symptoms-DiagnosisTreatment-Complications |
Medindia http://www.medindia.net/patients/patientinfo/chronicgranulomatous-disease.htm#ixzz1fa7vXQlO
Non-specific immunodeficiencies
Deficiencies of complement komponents:
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genetic disorders of complement system
involvement of regulatory proteins (e.g. herediter angioedema, C1INH deficiency)
vasodilatation, increased vascular permeability (capillaries)
edemas of skin and mucous membranes
Wiskott–Aldrich syndrome (WAS), XR
Eczema, thrombocytopenia, immune
deficiency, blood in stool (as a result of
thrombocytopenia).
Described by Aldrich (1954).
Secondary immundeficiencies
•
Tumors - especially disorders of bone marrow and periferial blood
(leukemia, lymphoma, multiple myeloma)
•
Iatrogenic factors
(immunosuppressive drugs, DMARDs, chemotherapy, radiotherapy)
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Malnutrition
Ageing
Some chronic infections
Aquired immunodeficiency syndrome (AIDS)
DMARDs - Disease-modifying antirheumatic drugs
AIDS
AIDS
Facialis sarcoidosis
Pneumocystis carinii cysts
AIDS
HIV/AIDS statistics - 2006
HIV
Membrane: from the membrane of the host
three glycoproteins: gp160, gp120 and gp41
gp41 is a transmembrane protein, gp120 is an ectoprotein associated to the
membrane non-covalently
HIV - cycle
internalization
Main target cell: CD4+T sejt
human HeLa
cell
ahumán HeLa cells
transfected by
CD4 antigen
No infection
Incected
HIV internalization into macrophages
Complications of AIDS
(opportunist pathogens)
Kaposi sarcoma