L21: Immunodeficiency Flashcards
What are immunodeficiency diseases
failure of the immune system
Primary ID
an individual is born with a genetic mutation that results in a defective immune response
Secondary ID
the individual is born with a normal immune response but experiences an event that damages the immune system.
how many primary ID are there
over 180
incidence of primary ID
1:5000 live births
what is the main clinical phenotype of 1° ID
increases suceptibilty to organisms that are of low pathogenicity in a healy person
explain the tree of immunodeficiency
primary and secondary - ID can occur in innate or adaptive IS
What are the defects in the innate immune system in primary immunodeficiency
- defects in:
- phagocyte response
- complement
What happens when there is a defect in the phagocyte repsonse (1ID)
defective phagocytes results in reccurent infections and fevers
what are the four types of phagocyte defects (1ID)
I. Deficiencies in production of phagocytes
II. Deficiencies in phagocyte adhesion
III. Deficiencies in phagocyte activation
IV. Deficiencies in phagocyte killing of microorganisms
What happens when there is leukocyte adhesion deficiencies
- integrin adhesion molecule defect (LFA1)
- absence of pus formation at the site of infeciton (no neutrophils)
- recurrent severe pyogenic bacterial and fungal infecitons with compromised wound healing
What is the purpose of LFA1
- adhesion molecule on outside of phagocyte → controls movement and trafficking of phagocytes along the endothelium
- Defect in protein - no trafficking - absence of pus (no neutrophils)
Chronic Granulomatous Disease
defect in phagocyte response - mutation of NADPH oxidase - cannot make ROS - failure to kill ingested bacteria
What happens when the classical pathway of the complement system is affected
no opsonisation by AB - clearance of infection reduced
what happens when there are defects in the C3 activation
deficiency leads to infection with pyogenic bacteria
what happens when the MAC is defect
only some bacteria are killed by MAC formation particularly neisseria → more susceptible to these species
defects in adaptive immunity (1° ID)
B cell - defects in B cell and AB production
T cell - disease in gene, functional defects
Wiskott-Aldrich sydrome (WAS)
defect in was gene - regulates lymphocyte development via its role in immune synapse formation
SCID
severe combined immunodeficiency
What are SCIDs
Mutations that result in comprised T and B cell “arms” of the immune system is a
- Combined Immune Deficiency
SCIDs incidence
1:50,000
when are SCIDs diagnosed
5 months after birth
how is SCIDs diagnosed
Lymphocyte numbers low in blood and lymphoid Tissue
- chronic diarrhea, failure to thrive and severe infections
Examples of SCID deficiencies
- Defects in nucleotide metabolism (deficiency in adenosine deaminase - increased dATP = toxic)
- X-linked SCID, mutations in genes encoding gamma chain of
interleukin receptors (T cells cant grow or mature)
treatment for SCID
- compatible bone marrow transplant
- gene therapy to restore correct gene
examples of secondary immunodeficiency
- aplastic anaemia
- drugs
- latent virus reactivation
- biofilms
what is aplastic anemia
- stem cells in the bone marrow are destroyed
- deficiency in RBC, WBC, platelets
treatment for aplastic anemia
blood transfusions, bone marrow transplantation,
antibiotics (when a bacterial infection has caused aplastic anemia)
how do cytotoxic chemotherapy drugs cause immunodeficiency
- destroy proliferating cells
- myelosuppresion
- neutropenia
