Immunology Blackboard Flashcards
1
Q
A. CD3 mutation B. Adenosine Deaminase (ADA) gene C. CD40 Ligand gene D. Bruton’s tyrosine kinase (Btk) gene E. IL12 gene F. IFN Receptor 1 gene G. WASP gene H. IL-2 receptor I. MHC Class III J. Chromosome 22q11 K. MHC Class II
- X-Linked Agammaglobulinaemia
- DiGeorge’s Syndrome
- Severe Combined Immunodeficiency
- Wiskott-Aldrich Syndrome
- This region encodes C2, C4 and factor B
- Hyper IgM syndrome
- Bare Lymphocyte syndrome
A
- Correct H. Bruton’s tyrosine kinase (Btk) gene - X linked agammaglubulinaemia
- DiGeorge’s Syndrome Correct B. Chromosome 22q11
- Correct C.
IL-2 receptor
Severe Combined Immunodeficiency. X-linked SCID is most common form (boys more likely to be affected), resulting from a mutation in the common γ-chain (γc) aka IL-2 receptor subunit gamma.
More severe form (reticular dysgenesis) has a mutation in adenylate kinase 2 enzyme = no granulocytes and lymphopaenia.
4. Wiskott-Aldrich Syndrome Correct J. WASP gene An X-linked thrombocytopaenia.
- This region encodes C2, C4 and factor B
Correct
E.
MHC Class III
Class III molecules have physiologic roles unlike classes I and II, but are encoded between them in the short arm of human chromosome 6. Class III molecules include several secreted proteins with immune functions: components of the complement system (such as C2, C4, and B factor), cytokines (such as TNF-α, LTA, and LTB), and heat shock proteins.
6. Hyper IgM sydrome Correct F. CD40 Ligand gene
- K - MHC Class II
Bare lymphocyte syndrome - type 2
Defect in one of the regulatory proteins involved in Class II gene expression - Regulatory factor X/ Class II transactivator
Lack of expression of class II MHC molecules results in:
- Profound deficiency of CD4+ cells
- Usually have normal number of CD8+ cells
- Normal number of B cells but failure to make IgG or IgA antibody
May be associated with scelorsing cholanigitis/failure to thrive.
E. IL12 gene
F. IFN Receptor 1 gene
Will result in susceptibility to mycobacteria and salmonella infections.
2
Q
- In acute rejection, release of this substance from CD8+ lymphocytes helps kill target cells
- In acute rejection, these are produced as a result of the activation of neutrophils and macrophages
- A difference in this between host and recipient is the main cause of transplant rejection
- Along with anti-HLA antibodies, the most important screen to ensure a match before transplantation
- Risk factor for chronic allograft rejection
- Transplanting an ABO incompatible kidney will result in ___ rejection
- Treatment of acute antibody mediated rejection
- Treatment of acute cell mediated rejection
- The 3 most important HLA types to screen for in renal transplantation when matching donor and recipient, in order of importance
- Lymphocyte that responds to foreign HLA DR types
- Lymphocyte that responds to foreign HLA A types
A
- In acute rejection, release of this substance from CD8+ lymphocytes helps kill target cells.
GRANZYME B - In acute rejection, these are produced as a result of the activation of neutrophils and macrophages
FREE RADICALS - A difference in this between host and recipient is the main cause of transplant rejection
HLA-TYPE - Along with anti-HLA antibodies, the most important screen to ensure a match before transplantation
ABO-TYPE - Risk factor for chronic allograft rejection
HYPEPTENSION - Transplanting an ABO incompatible kidney will result in ___ rejection
HYPERACUTE - Treatment of acute antibody mediated rejection
IVIG AND PLASMAPHERESIS - Treatment of acute cell mediated rejection
HIGH DOSE STEROIDS - The 3 most important HLA types to screen for in renal transplantation when matching donor and recipient, in order of importance
HLA-DR> B> A - Lymphocyte that responds to foreign HLA DR types
MHC-CLASS II = CD4 - Lymphocyte that responds to foreign HLA A types
MHC-CLASS I = CD8
3
Q
A. Ribavirin B. Ciclosporin C. Immunoglobulins D. Gentamicin E. Prednisolone F. Cyclophosamide G. Cyproterone acetate H. Chloramphenicol I. Perindopril J. Infliximab K. Mycophenolate mofetil L. Tofacitinib M. Metolazone N. Methotrexate O. Inteferon- alpha P Inteferon- Beta Q Inteferon- gamma R. Ipilimumab S. Pembrolizumab T. Nivolumab
Prevents DNA replication especially of T cells
Causes a transient increase in neutrophil count
Monoclonal antibodies inhibiting the actions of TNF
Can cause gingival hypertrophy as a side effect
Administration of this may boost the immune system
Used in hep B treatment
Monoclonal antibodies inhibiting the against CTLA4 in the treatment of advanced melanoma
Used in the treatment of RA and is a JAK inhibitor
Side effects include pneumonitis, pulmonary fibrosis and liver cirrhosis
A
- Prevents DNA replication especially of T cells - K. Mycophenolate mofetil blocks de novo nucleotide synthesis. Similar to azothioprine, affects T cells>Cells. (Risk of progressive multifocal leukoencephalopathy due to JC virus)
Cyclophosphamdide alkylates guanine, affects B cells> T cells. (May cause haemrrhagic cystitis due to acrolein toxin. Also cause infertility and hair loss) - Causes a transient increase in neutrophil count - E. Prednisolone
- Monoclonal antibodies inhibiting the actions of cytokines
- J. Infliximab Anti-TNF - Can cause gingival hypertrophy (and hirsutimsas a side effect - B. Ciclosporin. This is a calcineurin inhibitor as is tacrolimus. Calcineurin would otherwise up regulate il-2 expression in T cells. Calcineurin inhibitors may cause hypertension/are nephrotoxic - reduced GFR.
- Administration of this may boost the immune system - C. Immunoglobulins
- Used in hep B treatment - Interferon alpha
Hepatitis C, Hepatitis B, Kaposi’s sarcoma
(Interferon beta used for Relapsing MS in past)
(Interferon gamma used in Chronic granulomatous disease). Ribavarin may be added with IFN-alpha but is used more for Hep C than hep B. - Monoclonal antibodies inhibiting the against CTLA4 in the treatment of advanced melanoma - ipilimumab. Whilst pembrolizumab and nivolumab may be used in the treatment of advanced melanoma, they are antibodies against PD-1
- Used in the treatment of RA and is a JAK inhibitor - Tofacitinib.
- Apremilast is a PDE4-inhibitor used in psoriasis.
- For methotrexate (MTX) induced cirrhosis monitor serum procollagen III rather than doing liver biopsy. MTX is given once WEEKLY as maintenance therapy in autoimmune disease; more often and you’re looking at anti-tumour regimens. Remember to replace folate.
4
Q
B CELL DEFICIENCIES
Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE
Recurrent bacterial infections in a child, episode of pneumocystis pneumonia, high IgM, absent IgA and IgG
1 year old boy. Recurrent bacterial infections. CD4 and CD8 T cells present. B cells absent, IgG, IgA, IgM absent
Recurrent respiratory tract infections, absent IgA, normal IgM and IgG - IgA deficiency
A
- Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE - Common variable immunodeficiency - affects both sex equally and presents later on in life with Low IgG, IgA and IgE. In contrast to X-linked agammaglobulinemia, most individuals with common variable immunodeficiency have normal or near-normal numbers of B cells in the blood and lymphoid tissues. These B cells, however, are not able to differentiate into plasma cells.
- Recurrent bacterial infections in a child, episode of pneumocystis pneumonia, high IgM, absent IgA and IgG - X linked hyper IgM syndrome due to CD40 ligand mutation (T-cell defect to not provide cd40ligand)
- 1 year old boy. Recurrent bacterial infections. CD4 and CD8 T cells present. B cells absent, IgG, IgA, IgM absent -
Bruton’s X-linked hypogammaglobulinaema - Recurrent respiratory tract infections, absent IgA, normal IgM and IgG - IgA deficiency
Management involves
- IVIG infusion every 3-4 weeks
- BM transplant in SCID and X-linked hyper IGM
- Only IgA deficiency patients can be immunised out of the B cell deficiencies.
5
Q
- Severe recurrent infections from 3 months, CD4 and CD8 T cells absent, B cell present, IgM present, IgA and IgG absent
- Young adult with chronic infection with Mycobacterium marinum
- Recurrent infections in childhood, abnormal facial features, congenital heart disease, normal B cells, low T cells, low IgA and IgG
- 14 month baby with two recent serious bacterial infections. T cells present – but only CD8+ population. B cells present. IgM present but IgG absent
A
Severe recurrent infections from 3 months boy, CD4 and CD8 T cells absent, B cell present, IgM present, IgA and IgG absent - X linked SCID - IL-2 receptor mutation
Young adult with chronic infection with Mycobacterium marinum - IFN gamma receptor deficiency
Recurrent infections in childhood, abnormal facial features, congenital heart disease, normal B cells, low T cells, low IgA and IgG - DiGeorge Syndrome - CATCH - 22. Microdeletion detect using FISH.
14 month baby with two recent serious bacterial infections. T cells present – but only CD8+ population. B cells present. IgM present but IgG absent - Bare lymphocyte syndrome type II - regulatory factor X/ MHC class II more common.
6
Q
Anti-thymocyte globulin Basiliximab Natalizumab Tocilizumab Denosumab OKT3 (muromonab-CD3) Etanercept. Abatacept Ustekinumab Rituximab Methotrexate/Cyclosporine
- Inhibits T cell migration but may only be used in highly active remitting/relapsing MS
- Inhibits T cell activation and is effective in rheumatoid arthritis. IgG1 fused to the extracellular domain of CTLA-4.
- Depletes B cells and is effective in treatment of B cell lymphomas and rheumatoid arthritis
- Inhibits function of lymphoid and myeloid cells and used in management of rheumatoid arthritis and castlemans disease.
- Used in allograft rejection (renal/heart)
- Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
- Inhibit RANK ligand for Osteoporosis
- Inhibit IL12/23 for Psoriasis
- TNF receptor p75-IgG fusion protein. Used for RA and Psoriasis
- Used as an immunosuppression inducation agent and in treatment of acute corticosteroid-resistant rejection of renal, heart and liver transplants
- What is prophylaxis and treatment of GvHD?
A
- Natalizumab (Anti-alpha 4 integrin)
Natalizumab – anti-a4 integrin - Antibody specific for a4 integrin. A4 is expressed with B1 or B7 integrin. It binds to VCAM1 and MadCAM1 to mediate rolling/arrest of leukocytes. Used in treating multiple sclerosis - Abatacept – CTLA4-Ig - IgG1 fused to the extracellular domain of CTLA-4. Rheumatoid arthritis -Intravenous 4 weekly. Rheumatoid arthritis -Intravenous 4 weekly
- Rituximab (Anti-CD20) - Depletes B cells and is effective in treatment of B cell lymphomas and rheumatoid arthritis.
- Tocilizumab – anti-IL-6 receptor. Used to treat castleman’s disease. Tocilizumab (Anti-IL-6 receptor) Inhibits function of lymphoid and myeloid cells and used in management of rheumatoid arthritis and castlemans disease.
- Rabbit anti-thymocyte globulin - used in allograft rejection (renal/heart)
- Basiliximab – anti-CD25/ IL-2ra - Prophylaxis of allograft rejection. Intravenous given before and after transplant surgery. Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
- Denosumab: Inhibit RANK ligand for Osteoporosis. Given subcut every 6months. May cause avascular necrosis of jaw.
- Ustekinumab -Antibody to p40 subunit of IL-12 and IL-23, used in treatment of Psoriasis.
- TNF receptor p75-IgG fusion protein. Used for RA and Psoriasis
- OKT3 (muromonab-CD3; F) is a mouse monoclonal antibody targeted at the human CD3 molecule used to treat rejection episodes in patients who have undergone allograft transplantation.
Treatment of episodes of acute rejection:
Cellular: steroids, ATG/OKT3
Antibody-mediated: IVIG, plasma exchange, anti-C5, anti-CD20 - GVHD prophylaxis: Methotrexate/Cyclosporine
Acute GVHD happens in days and may cause jaundice and bloody diarhoea. Chronic GVHD gives similar symptoms to systemic scelorsis. treat with steroids.
