Immunodeficiency Diseases Flashcards
1
Q
What is classed as Secondary immunodeficiency?
- commonality?
- causes?
A
- Immune defect is secondary to another disease process
- Very common
- Extremes of age
- Malignancies (esp myeloma, lymphoma)
- Metabolic eg diabetes
- Drugs eg chemotherapy, steroids
- Infection eg HIV
2
Q
What is classed as Primary immunodeficiency syndrome (PID)?
- commonality?
- causes?
A
- Immune defect is intrinsic to the immune system itself
- Rare
- Often genetic, but not always
- Over 100 characterised PIDS
- Mostly are fairly ‘new’ diseases
- Fatal in pre-antibiotic era
- Characterisation required developments in technology
3
Q
What is Immunosenescence?
A
‘A combination of age-related changes in the immune system that result in greater susceptibility to infection and reduced response to vaccination’
- many other factors of old age that impact this
4
Q
What is Combined Immunodeficiencies
A
- Immunodeficiency syndromes affecting both antibody production (B cells) and T cells
5
Q
What is Immune dysregulation?
A
uncontrolled inflammation, autoimmune diseases
6
Q
What are some immunological aspects of immunosenescence?
A
- Thymic involution
- Telomere shortening in stem cells reduces both quality and quantity of leucocyte output
- Reduced T and B cell receptor diversity
- Reduced vaccine responses
- Reduced neutrophil function
- Reduced self-tolerance; inflammation switches from protection to damage
- Expansion of T cell pool responding to cytomegalovirus (current research focus)
7
Q
What are some key features of Primary Immunodeficiency?
A
- Low IgG; other isotypes may be affected, but low IgA/ M with normal IgG is rarely significant
- Manifests with recurrent pyogenic infections of the upper and lower respiratory tract
- Sometimes gut infections in addition
- Infections typically respond to anti-microbials, but response may be sub-optimal and long courses required
- If untreated, leads to irreversible lung damage (bronchiectasis)
8
Q
What are the causes of antibody deficiency?
- Physiological
- Secondary
- Primary
A
Physiological
- Transient hypogammaglobulinemia of infancy
Secondary
- IgG loss:
- Renal: nephrotic syndrome
- Skin: extensive burns
- Impaired production:
- Immunosuppressive drugs
Primary
- X-Linked agammaglobulinemia
- X-Linked hyper-IgM syndrome
- (Common variable immunodeficiency – module 302)
- Many others that are beyond scope
9
Q
What is transient hypogammaglobulinemia of infancy?
A
- In healthy infants there is normally a period of relative antibody deficiency around 6 months known as ‘transient hypogammaglobulinemia of infancy; this is a physiological state but can be correlated with increased infections
- Infants with antibody deficiency usually present after 3-6 months; up until this time they are protected by maternal IgG antibody
10
Q
What is XLA?
A
- a prototype antibody deficiency syndrome
- Signalling via Bruton’s tyrosine kinase (btk) required for signal transduction at pro-B stage
- Maturation arrest occurs if absent: no heavy chain rearrangement, no B cells leave marrow, no immunoglobulin production
- Disease is called X-linked agammaglobulinaemia (XLA); also known as Bruton’s disease, Btk deficiency or Bruton’s XLA
11
Q
What s X-linked hyper IgM syndrome?
A
- CD40L deficiency
- Failure of B cell maturation from primary to secondary
- Low IgG & IgA, raised (or normal) IgM
- Recurrent bacterial infections
- Presents age 3-6 months
- The immunological lesion actually resides on the T cell
- CD40 ligand (also known as CD154)
- Interaction with CD40 on B cells required for affinity maturation, however as this isn’t present maturation doesn’t occur
12
Q
How are antibody deficiencies treated?
A
- Early recognition before lung damage occurs
- Aggressive treatment of intercurrent infections
- Replace immunoglobulin
- Long-term suppressive anti-microbials
13
Q
What is Cellular immunodeficiency?
- manifestation/ presentation
A
- CD4 T cell deficiency
- When congenital, antibodies will also be affected (combined immunodeficiency)
- Manifests particularly with:
- Opportunistic infection
- Viral infection
- Fungal infection
- Mycobacterial infection
- Classic secondary cause is HIV infection
14
Q
What are some conditions seen in cellular immunodeficiency especially in advanced HIV?
A
- Candida oesophagitis
- Cytomegalovirus retinitis
- Kaposi’s sarcoma - driven by Herpes virus infection
- Pneumocystis jiroveci pneumonia
- Cerebral toxixplasmosis
15
Q
What is Severe Combined Immunodeficiency disease (SCID)
- presentation?
A
- Rare, life-threatening primary immunodeficiency
- Absent T cells
- B cells may be present, but are non-functional
- All basically present in a similar fashion
- Usually soon after birth
- Rash (graft versus host - maternal lymphocyte engraftment)
- Failure to thrive
- Chronic diarrhoea
- Infections, especially opportunistic
- Bacterial
- Mycobacterial (esp BCG)
- Viral (esp CMV, EBV)
- Fungal (PCP, oral thrush)
