Immunology Flashcards
What complement deficiencies lead to an SLE-like condition and how does this occur?
C1, C4 and C2 Inability to clear self antigens
What complement deficiencies lead to increased risk of Neisseria?
Lytic phase complements - C5-C9 Alternative pathway - Factor D and properdin
What are the phagocytic immunodeficiencies?
Chronic granulomatous disease Cyclic neutropenia Neutrophil G6PD deficiency Leukocyte adhesion deficiency Myeloperoxidase deficiency
What are the features of phagocytic immunodeficiencies?
Deep seated infections Bacterial and fungal infections Delayed separation of cord
What are the clinical features of antibody/humoral immunodeficiency?
Mucosal infections S. pneumoniae and haemophilus Chronic diarrhoea esp due to giardia and gut infections Autoimmune cytopenias
What are the common antibody immunodeficiencies?
Common variable immunodeficiency
X-linked agammaglobulinaemia
Combined immunodeficiency
Good syndrome
Specific antibody deficiencies
What are the steps for the migration of leuokocytes?
Rolling adhesion
Tight binding
Diapedesis
Migrations
What are the complement activation pathways?
Classic
MBLECTIN
Alternative (via pathogens)
All come together at C3
Which cells express MHC1, which express MHC2?
MHC 1 - found on all nulceated cells. Recognised by CD8+ cells
MHC II - found on professional antigen presenting cells. Recognised by CD4+ cells
What are the T helper subsets and what are their roles?
Th1 - activates macrophages, induces B cells
Th2 - activates B cells, various effects on macrophages, promotes IgE
Th17 - protects against intracellular pathogens
Treg - secretes anti-inflammatory cytokines eg IL-10 and TGFb
What is the role of each of the immunoglobulin classes?
IgM - complement activation
IgG - opsonisation, complement activation. Switch triggered by INF-y
IgE - immunity against helminths, mast cell degranulation. Switch triggered by IL-4
IgA - mucosal immunity
What are the types of hypersensitivity reactions?
Type I - immediate (classic allergy)
Type II - cytotoxic reaction - antibody dependant (haemolytic anaemia, goodpastures)
Type III - immune complex reaction (vasculitis)
Type IV - delayed - cell mediated (contact dermatitis, asthma)
What are the disease associations with C-ANCA? What is its other name?
PR3-ANCA
Granulomatosis with polyangiitis >90%
Microscopic polyangiitis 30%
Associated with more frequent relapses
What are the disease associations with P-ANCA? What is its other name?
MPO-ANCA
Microscopic polyangiitis
Eosinophilic granulomatosis with polyangiitis
What is the treatment for ANCA associated vasculitis?
Induction with steroids + cyclophosphamide (some switch to AZA)
Maintanence with AZA or MTX
Maintaince therapy for 2-3 years
Bactrim prophylaxis
What drugs can cause an ANCA associated vasculitis?
Propythiouracil
Hydralazine
Allopurinol
Sulphasalazine
Minocycline
Cefotaxime
Ciprofloxacin
Clozapine
Which ANCA type is associated with frequent relapses?
PR3-ANCA (c-ANCA)
What is the classic renal picture with microscopic polyangiitis?
Primary pauciimmune necrotising GN
What is the treatment for temporal arteriitis?
Steroids tappered over 1-2 years
Methotrexate can be used as a steroid sparing agent
Tocilizumab (anti-IL6) can be used for refractory cases
Disease activity monitored clinically and with ESR/CRP
What is the HLA association with Behcets disease?
HLA-B51
What is the management with Behcets?
Topical steroids
PO prednisone if refractory
Colchicine useful for arthitis
Can use immunosuppression if refractory - AZA, anti-TNF, cyclosporin
What is the pathophysiology of X-linked severe combined immunodeficiency?
There is a mutation in the common y-chain of the cytokine receptors found on lymphocytes. The lack of activity of teh cytokines notably IL-7 means there is no T-cell development. While B cells can still develop the lack of T-cells causes a lack of stinumation and therefore lack of antibody synthesis. IL-15 is required for NK cell maturation so they are also lacking
What are the clinical findings of severe combined immunodeficiency? What is the treatment?
Often males as majority is x-linked SCIDs but can be autosomal recessive
Presentation within 1st year of life
Widespead severe infections eg PJP, HSV, candida, pseudomonas. Can get GVHD from maternal T cells which cross the placenta. Small thymus, hypoplastic lymphoid tissue
Treatment is AlloSCT within 1 year of life or gene therapy for X-linked
What is the mutation which causes x-linked agammaglobulinaemia?
A mutation in Bruton tyrosine kinase
What is DiGeorge syndrome?
Caused by 22q11 deletion leading to failure of development of the 3rd and 4th pharyngeal pouches. This causes:
Abscent thymus and lack of T cell development (normal or reduced antibody levels) - fungal and viral infections
Abscent parathyroids - tetany
Defects of heart and great vessels
Abnormal appearance of facial features
What are the clinical features of X linked agammaglobulinaemia?
Recurrent respiratory/mucosal infections after 6 months of age
Notably S. aureus, haemophilus, and s. pneumonia
Giardia (needs IgA for opsonization)
Enteroviruses
**all other viral, fungal and protezoal infections can be managed
What infections are seen with each deficiency? (T cell, B cell, granulocyte, complement)
What are the 6 HLA subclasses?
MHC I - HLA A, HLA B, HLA C
MHC II - HLA DP, HLA DQ, HLA DR
Where are the HLA (MHC) genes located?
On chromosome 6
What is the physiology of CTLA-4
Found on T cells
It has a significantly higher affinity for CD80/86(APC) than CD28(T cell) therefore preventing the second signal for T cell activation.
Repeated activation upregulates CTLA-4
Which checkpoint inhibitor is most associated with thyroid disease?
PD-1
Which checkpoint inhibitor is most associated with colitis?
CTLA-4
