Immunodeficiency Flashcards
What is the role of pattern recognition receptors (PRRs) in the immune system?
PRRs are structures found on cells of the innate immune system (eg. dendritic cells, macrophages etc.) they tell you what kind of pathogen you are dealing with and thus enable the innate immune system to instruct the adaptive immune system as to what is the most appropriate type of response through production of different chemokines etc.
(PRRs wouldnt be able to tell you the exact species of pathogen but they could tell you if it was a gram-negative bacteria, a fungus, a virus etc)
What are the 5 major components of the innate immune system?
1) Pattern recognition receptors
2) Antimicrobial peptides
3) Cells
4) Complement components
5) Cytokines
What is the function of B lymphocytes?
Develop potential to secret antibodies
What is the function of CD4+ cells?
(Helper T cells) secrete growth factors (cytokines) which control immune response: help B and T lymphocytes - instruct proper maturation of B cells aswell as cytotoxic T cells
In what 4 ways can binding of antibodies to antigens inactivate those antigens?
1) Neutralization (blocks viral binding sites/coats bacteria)
2) Agglutination of microbes (stick in a big lump)
3) Precipitation of dissolved antigens
The above 3 processes enhance phagocytosis by macrophages
4) Activation of complement system
The above leads to cell lysis
How do cytotoxic T cells kill infected cells?
Cytotoxic T cell binds to the Ag presented on the surface of the infected cell
Releases perforin molecule which makes holes in the infected cells membrane and an enzyme promoting apoptosis is released by the cytotoxic T cell which can now enter the infected cell and destroy it
What is meant by immunodeficiency?
Clinical situations where the immune system is not effective enough to protect the body against infection
Does immune deficiency only present in children?
No it can occur at any age but its important to remember that children and the elderly are much more sensitive to infection
What is the difference between primary and secondary immunodeficiency?
Primary - caused by genetic defects in individual components of the immune system
Secondary - immunodeficiencies secondary to the effects of external factors
What is often a guide to the underlying cause of immunodeficiency in patients, and what confirms it?
Type of infection is often a guide to the underlying cause of the immunodeficiency, laboratory tests confirm the cause
Are immunodeficiencies always permanent?
No secondary immunodeficiencies can be transient or long lasting
Give 8 external factors which can cause secondary immunodeficiency?
1) Stress
2) Surgery/burns
3) Malnutrition
4) Cancer - especially lymphoproliferative disease
5) Immunosuppressive effect of drugs inc. cancer therapy
6) Irradiation
7) AIDS
8) Other infections eg. measles or TB
How common are primary immunodeficiencies?
Very rare
When are primary immunodeficiencies typically diagnosed?
In early childhood (note they can present later on in life)
Why is family history important to consider when considering a diagnosis of primary immunodeficiency?
Caused by genetic defects
What investigations would you carry out when considering a diagnosis of primary immunodeficiency in a person presenting with recurrent or unusual infections? 4
1) Immunoglobulin levels - indicates B cell function
2) Lymphocyte levels
3) Neutrophil levels
4) May test CRP if current infection to see if actually mounting an inflammatory response
What role does IRAK have in immune response?
Formed as part of the intracellular signalling pathway of toll like receptors (a type of PRR) when they encounter a pathogen - forms NF-kbeta which is a transcriptional factor which leads to the release of inflammatory cytokines/chemokines which leads to inflammatory and adaptive immune response
Why would an IRAK deficiency cause immunodeficiency?.
Because IRAK is a key component in the pathway to release of inflammatory cytokines/chemokines from the cells of the innate immune system which plays a role in the development of an adaptive and inflammatory response
Which test could be carried out to determine neutrophil function?
Nitroblue tetrazolium test (NBT)
What is the mechanism of phagocytosis?
1) NADPH releases H+
2) H+ transported into the phagosome via a specific proton channel
3) This lowers the pH within the phagosome which tiggers the proteolytic enzymes within the phagosome which can destroy the material within it
What is the defect in chronic granulomatous disease?
An inherited disorder of phagocytic cells resulting in an inability to phagocytose pathogenic material
What kind of mutation is chronic granulomatous disease normally caused by?
X-linked mutation
Would patients with chronic granulomatous disease have a reduced number of neutrophils?
No, they would have a normal number of neutrophils but they would be stuffed full of pathogenic material that they wouldnt be able to destroy
Why does chronic inflammation tend to occur in chronic granulomatous disease (CGD)?
As neutrophils are malfunctioning the rest of the immune system components has a frustrated response which leads to inflammation
What are the 6 complications of chronic granulomatous disease (CGD)?
1) Osteomyelitis
2) Pneumonia
3) Swollen lymph nodes
4) Gingivitis
5) Non-malignant granulomas
6) Inflammatory bowel disease
How would you test terminal complement function?
1) Take sheep RBC’s, incubate with patient serum - human RBCs have structures on the surface which inhibit our own complement system, sheep RBCs dont have this
2) If complement is functioning properly all the sheep RBCs should undergo haemolysis
What are the key steps in the common terminal complement activation pathway?
1) Activation of C3 convertase which cleaves C5
2) Cleaving of C5 to C5b allows the rest of the complement (C6-C9) to set on the surface of the bacteria and create pores which leads to the lysis of susceptible microorganisms
X-linked agammaglobulinaemia (XLA) is an immunodeficiency with defects in what?
B cells
What kind of infection do immunodeficiencies with defects in B cells lead to?
Recurrent bacterial infection with pyogenic organisms
Why are defects in B cells usually diagnosed only around 1-2 years?
Maternal IgG protects until this point
How are B cell defects treated?
Treat with Abx and IV IgG from a pool of donors for life
Name 6 primary B cell deficiencies?
1) Common variable immunodeficiency
2) x-linked agammaglobulinaemia
3) Autosomal recessive Hyper IgM syndrome
4) IgA deficiency
5) IgG subclass deficiency
6) Transient Hypogammaglobulinaemia of infancy
Why are primary immunodeficiencies caused by autosomal recessive or x-linked mutations?
Immunodeficiencies are due to a loss in function, need both mutated alleles to aquire that loss of function, so must be recessive or x-linked
Why would a severe extensive candida infection indicate an immunodeficiency?
Because candida doesn’t normally cause this kind of infection in healthy people
What may be the presentation of chicken pox in a immunodeficient baby compared to a health baby?
Get fulminant (severe and sudden onset) disease rather than mild disease Get haemorrhagic lesions as opposed to the typical vesicles of chicken pox
Severe combined immunodeficiency syndromes (SCID) refers to defects in what 2 kinds of cells?
1) B lymphocytes
2) T lymphocytes
What are the symptoms of SCID?
Recurrent infection with opportunistic infections: bacteria, viruses, fungi (candida) and protozoa (pneumocystis)
What are the 2 treatments for SCID?
1) Bone marrow transplant is curative
2) Gene therapy
Name 4 primary T cell deficiencies?
1) Adenosine deaminase deficiency
2) Purine nucleoside phosphorylase deficiency
3) MHC class II deficiency
4) Wiskott-Aldrich syndrome
Defects in PRRs normally present with what 2 infections?
1) Pneumococcus
2) HSV
Defects in macrophages and neutrophils usually present with what 2 infections?
1) Staphylococcus
2) Aspergillus
Defects in complement often present with what infection?
1) Meningococcus
Defects in cytokines normally present with what kind of infection?
Mycobacterium
Defects in B cells normally present with what kind of infection?
Recurrent sino-pulmonary infections
