Lecture 11 - Immunodeficiencies Flashcards
What is innate immunity made up of?
First line:
• Physical barriers
• pH
• Secretions
Second line:
• Innate immune cells
Describe the role of DC’s
- ‘Sentinels’
- Link between innate and adaptive immunity
- PAMP recognition with PRRs
- T-lymphocyte co-stimulation
- Nature of their function dependent on cytokine signalling
What are the critical features of adaptive immunity?
- Slower to be induced
- Memory function
- Recognises specific antigen
What are the different type of B cells?
- B-1
- B-2
- Marginal zone B cells (MZB)
- Follicular B cells
Describe the kinetics of immune protection after vaccination
→ Vaccination
- Induction of the primary immune response; IgM
- Response dies back, pool of memory cells present
→ Exposure to antigen from environment
3. Induction of immune response more quickly and to a greater magnitude; IgG, IgA
What are the main difference between the primary and secondary immune responses?
Secondary:
• greater magnitude
• more quickly induced
• class switched Ig (e.g. IgG, IgA)
Can IgA or IgM be monomers?
IgM: no
IgA: yes
What is the structure and function of memory B cells?
- Surface bound immunoglobulins
* hang around after the immune response has been resolved, waiting for the next exposure to the antigen
Compare T-dep. and T-independent antigen, and the respective immune responses
T-dependent:
• usually protein
• T cell help available to B cells
→ longer lived, more robust response
T-independent: • polysaccharide • no T cell help available to B cells → short lived response • no SHM or CSR
Describe the role and function of Treg
Suppressive effects on: • granulocytes • DC's • B cells • Th2 • Th1 • Th17 • T cell migration to tissues Under normal conditions, control allergy, autoimmunity and inflammation
What are the markers of Treg?
Why is this important?
- CD25
- CD4
• FoxP3 (transcription factor)
Deficiency in FoxP3 leads to deficiency of Treg.
This is called IPEX syndrome
What are the generalised outcomes of immune system defects?
- Autoimmunity
- Allergy
- Immunodeficiency
Define Immunodeficiency
A group of disorders where part of the immune system is missing or defective
What are the two categories of immunodeficiency?
Give examples for each
Primary: inherited (HIGM)
Secondary: acquired (HIV/AIDS)
What is PID?
Describe some features.
When is the onset?
What are the various classes?
Primary immune deficiency
• 150 different conditions
• most are rare
• inherited
Onset is usually in childhood, but can in adulthood
Classes in order of prevalence: • Antibody • Combined • Phagocytic • Cellular • Complement
What are clinical signs of PID used for diagnosis?
Combination of patient history w/ lab tests
Patient history: • >10 cases of otitis media per year • >2 cases of pneumonia • >2 life threatening infections per lifetime • >2 sinus infections per year
Lab tests:
• Low Ig levels (in general, or of specific classes)
• Cellular deficiencies
What are the pathological features of PID?
• Recurrent deep skin or organ abscesses
• >2 deep-seated infections such as meningitis,
osteomyelitis, cellulitis or sepsis
- oral thrush or Candida infection
- Autoimmune phenomena
- Dysmorphic features associated with recurrent infection
- Infections that worsen chronic disorders (eg. asthma)
- Infections with pathogen despite vaccine (eg pneumococcal)
Give some specific examples of PID
- T cell
• IPEX
• SCID - B cells
• CVID
• SAD - Innate deficiency
• Chronic granulomatous disease
• IRAK-4
What are some Antibody deficiencies?
- CVID
- SAD
(HIGM, agammaglobulinaemia; but these aren’t death with in this lecture)
What are some T-cell deficiencies?
- SCID (severe combined immune deficiency)
* IPEX syndrome
Describe the general features CVID
What is the cause?
Normal numbers of B cells, but they do not develop properly in plasma cells to produce Ab
- One of the most common PID’s
- V. low levels of serum Ig
- Increased susceptibility to infection due to this Ab deficiency
• Affects multiple organs (lungs, GIT, spleen, ears, blood)
Causes: Mutations in: • TACI • ICOS • CD19
What are the pathological outcomes of CVID seen around the body?
1. Frequent lung infections • Sinusitis • Pneumonia • Bronchitis • Otisis
- Enlarged lymph nodes & spleen
- Polyarthritis
What are the treatment options for CVID?
What about SAD?
- Intragam (IVIg)
- Antibiotics for the infections
Same for SAD
What is the main features of SAD?
What is lacking?
What isn’t?
(Specific antibody deficiency)
• Failure to produce normal Ab levels against specific polysaccharide antigens
(IgG2?)
NB
• Normal general Ig levels, and normal Ig subclasses, and normal response to protein antigens
• It is only Ig against very specific antigens that are absent
