Immunodeficiency (9.1) Flashcards
Distinguish primary and secondary immunodeficiencies
Primary: Inherited disorder of the immune system resultant of mutations in 1 or more genes associated with immune function.
Secondary: Acquired during life following an ‘insult’ to the immuen system. Individuals are born with a normal functing immune system
Outline the nature of infections associated with immunodeficiencies in general and with immunodeficiencies affecting different components of the immune system
Outline the main features of primary and secondary antibodies deficiencies
Lead to:
Bacterial infections (ENT)
Autoimmune reactions
Malignancy
Permanant damage (e.g. brochiecstasis)
Indicates the points in B cell development and maturation pathways affected in different antibody deficiencies
Draw pathway of Ig production
Explain the nature and consequences of DiGeorge Syndrome as an example of a primary T cell deficiency
PRIMARY T CELL DEFECT - Resultant of failed development of the 3rd and 4th pharyngeal/brachial arches
Development defects are seen in the region of the lower face to the chest:
Failed development of the thymus → T cell deficency
Lack of parathyroid glands → Hypocalcaemia
Failure of great vessel formation → Congential heart disease
Facial dysmorphia
Consequences:
Increased susceptibilty to GvHD, viral and fungal infection
Outline the main features of HIV infection and AIDS and give examples of opportunistic infections in AIDS
HIV infects CD4+ cells (T cells, MCs and DCs), through its gp120 receptor. The R5 virus also interacts with CCR5 (T cells, MCs and DCs) and the CX4 virus interacts with the CXC4 (T cells).
gp41 allows for fusion of the virus with host cells.
Infection of DCs (present at mucosal surfaces) allows for spread of the virus to lymph nodes and subsequently to T cells.
HIV induces CD4 cell death through lysis, immune activation, apoptosis, thymic impairment etc.
Mutation in the virus allow for immune evasion (error prone reverse transcriptase)
Route of infection include sexual intercourse (DCs at mucosal surfaces), maternal-foetal and via blood products.
Opportunistic infections include:
- Kaposi’s sarcoma
- Toxoplasma gondii → cerebral abscesses
- Pneumocystis jirovecci → pneumonia
- Cryptosporidium in the gut
Outline the nature and consequences of severe combined immunodeficiency (SCID)
Presentation
A PRIMARY immunodeficiency resultant of an inherited stem cell defect. Resultantly there are no functional T and B cells. Various types of SCID
No lymphocytes → no adaptive immune system → highly susceptible to infection
Presents in the first year of life. Multiple infections.
Results in death if untreated.
Cured through bone marrow transplant
Describe the nature and consequences of deficiencies that affect neutrophils and complement proteins
Defects in innate immunity
Neutrophil defect: Major granulocyte
May be a primary or secondary defect. The defect may lead to absence of neutrophils or decreased/absent functionality.
Kostmann’s disease: Lack of neutrophil production
Leukocyte Adhesion Deficiency (LAD): Mutation in integrin, preventing them migration of neutrophils to the site of infection. Profound effects result.
Chronic granulomatous disease: Defects in the production of enzymes and ROS cause loss of abilty to kill pathogens.
Complement defects
Generally causes increased susceptibilty to bacterial infection.
Failure of MAC formation → increased susceptibilty to Neisseria infection.
Immune complex accumulation: C3b is used to bind post-infection circulating immune complexes. RBCs express C3b receptors, allowing for binding. The immune complexes are then destroyed within the spleen or liver as RBCs pass through. Loss of C3b production leads to accumulation of immune complexes - which may provoke autoimmune diseases or renal pathology.
Loss of C1q production → Lupus
Outline the main categories of secondary immunodeficiencies
Iatrogenic: Immunosuppressants, lymphoid tissue removal
Lymphoproliferative: Leukaemia, lymphoma, myeloma
Renal/GI loss
Malnutrition
Some infections: HIV, chronic malaria, measles
Some chronic diseases: Renal failure
Burns
