Immunology Flashcards
HLA class I
- Presents to
- Main subtypes
- CD8+ T cells
2. Groups A, B and C
HLA class II
- Presents to
- Main subtypes
- CD4+ T cells
2. Groups DR, DQ, DP
Most important subtypes for HLA matching
HLA A, B and DR
Screen for HLA type using which technique?
PCR-based DNA sequence analysis
Screen for anti-HLA antibodies using which three techniques?
- Cytotoxicity assays
- Flow cytometry
- Solid phase assays
Anti-CD52 (suppresses T cell response, used for pre-transplant induction)
Alemtuzumab
Anti-CD25 (suppresses T cell response, used for pre-transplant induction)
Basiliximab
Baseline immunosuppressants used post-transplant to reduce rejection
Calcineurin inhibitors, mycophenolate mofetil and azathioprine
Anti-CD20 (destroys B cells)
Rituximab
Treatment of episodes of acute rejection:
- cellular?
- antibody-mediated?
Cellular: steroids, ATG, OKT3
Antibody-mediated: IVIG, plasma exchange, anti-C5 (Eculizumab), anti-CD20 (Rituximab)
Eliminate host immune system before haematopoietic stem cell transplant using?
Cyclophosphomide
GVHD prophylaxis
Methotrexate / cyclosporin
Treat acute GVHD with?
Corticosteroids
Kaposi’s sarcoma associated virus
HHV8
Live vaccines
MMR Chickenpox Yellow fever Typhoid BCG Polio (oral sabin)
CD45 RO T cells
Memory T cells
CD45 RA T cells
Naive T cells
Central memory T cells found in lymph nodes and tonsils
More CD4, CCR7+ve and CD62L+ve (allow entry via high endothelial venules), produce IL2
Effector memory T cells founds in liver, lungs and gut
More CD8, CCR7-ve, CD62L-ve, produce perforin and IFN-gamma
T helper cell response
- Th1
- Th2
Th1 = cell mediated, involves cytokines IL-2, IFN-gamma, TNF Th2 = antibody mediated, involves cytokines IL-4, IL-5, IL-6
Pavalizumab
Monoclonal antibody for RSV
Adjuvant which provides slow-release antigen to help prime immune response. Activates Gr1+ cells to produce IL-4 –> helps prime naive B cells. Stimulates monocytes into DCs (primes adaptive response).
ALUM
Unmethylated motif with 2 purines at 5’ end and 2 pyrimidines at 3’ end - acts as an immunostimulatory adjuvant. Activates TLRs (PRRs) on APCs stimulating expression of costimulatory molecules.
CpG
Water-in-oil emulsion containing mycobacterial cell wall components. Mainly for animals, painful for humans.
Complete Freund’s adjuvant
Experimental - multimeric antigen with adjuvant built in
ISCOMS
Passive vaccine HNIG
Hep A and measles
Encapsulated bacteria
Streptococcus pneumoniae Group B Strep. Haemophilus influenzae Neisseria meningitidies (meningococcus) Klebsiella Salmonella typhi
Test for classical pathway deficiency
CH50
Test for alternative pathway deficiency
AP50
Type I hypersensitivity reaction
Immediate IgE-mediated
Type II hypersensitivity
Antibody reacts with cellular antigen
Type III hypersensitivity
Antibody reacts with soluble antigen to form an immune complex
Type IV hypersensitivity
Delayed type hypersensitivity - T cell mediated
Diseases associated with ANA
SLE, Sjogren’s syndrome, systemic sclerosis, dermatomyositis, polymyositis
Rheumatoid arthritis antibody
Anti-CCP
Crescentic nephritis
Goodpasture’s disease
What is rheumatoid factor?
IgM anti-IgG
C1 esterase deficiency
Hereditary angioedema
Smooth linear deposition of antibody along GBM
Goodpasture’s disease
“Lumpy-bumpy” pattern of antibody complex deposition in basement membrane
SLE
Causes of high ESR
Myeloma, SLE and Sjogrens
Low complement indicates?
Severe disease activity
What type of reaction is dermatomyositis?
Type III (perivascular CD4 T cells and B cells)
What type of reaction is polymyositis?
Type IV (CD8 T cells kill myofibres via perforin / granzymes)
Associated with ANCA and chronic Hep B
Polyarteritis nodosa
Small vessel vasculitis (ANCA associated)
Microscopic polyangiitis
Granulomatosis with polyangiitis (Wegener’s)
Eosinophilic granulomatosis with polyangitis (Churg-Strauss)
Small vessel vasculitis (immune complex associated)
Goodpasture’s disease
IgA nephropathy (Berger’s)
Cryoglobulinaemia
Haematuria a couple of days after URTI
Berger’s IgA nephropathy
Haematuria a few weeks after URTI
Post-streptococcal glomerulonephritis
c-ANCA
Wegener’s granulomatosis with polyangiitis
p-ANCA
Churg-Strauss (eGPA) and microscopic polyangiitis
Acute transplant rejection is:
- Mediated by what cell type?
- Treated how?
- T cells
2. Corticosteroids
Treatment of antibody-mediated rejection
IVIG and plasmapharesis
Order of importance of HLA types in transplant rejection
HLA DR > B > A
Drug blocking DNA synthesis, especially of T cells
Mycophenolate mofetil
Causes a transient increase in neutrophil count
Prednisolone
Anti-TNF alpha
Infliximab and Adalimumab
Side effect is gingival hypertrophy
Ciclosporin
Test to confirm anaphylaxis
Mast cell tryptase levels (peak 1-2 hours, normalised by 6 hours)
Causes of IgE-mediated mast cell degranulation–> anaphylaxis
Peanut, penicillin, wasp or bee venom, latex
Causes of non-IgE-mediated mast cell degranulation –> anaphylaxis
Aspirin and NSAIDs, IV contrast media, opioid analgesics, exercise
Cause of drug-induced angioedema
ACE inhibitors
Inactivated vaccines
Hep A Rabies Whole cell ertussis Influenza Polio (salk)
Component vaccines
Hep B (HbS)
HPV (capsid)
Influenza (haemagglutinin, neuraminidase)
Conjugate vaccines
Tetanus (exotoxin)
HiB
Toxoid vaccines
Diptheria
Tetanus
Preferred host target of HIV
CD4+ T cells
HIV: attachment inhibitor
Maraviroc
HIV: fusion inhibitor
Enfuvirtide
HIV: nucleoside reverse transcription inhibitor
Zidovudine (aka azidothymidine)
HIV: non-nucleoside reverse transcription inhibitor
Efavirenz
HIV: integrase inhibitor
Raltegravir
HIV: protease inhibitor
Saquinavir
Th1 CD4+ T cells produce
IL-2, IFN-gamma and lymphotoxin
Th2 CD4+ T cells produce
IL-4, IL-5 and IL-10
Th17 cells secrete
IL-17 and IL-22
T reg cells express and secrete
Express CD25 and FoxP3
Secrete IL-10
Tr1 cells secrete
IL-10 and TGF beta
Ankylosing spondylitis HLA association
HLA B27
Goodpasture’s syndrome HLA association
HLA DR15 / DR2
Graves disease HLA association
HLA DR3
SLE HLA association
HLA DR3
T1DM HLA association
HLA DR3 / DR4
Rheumatoid arthritis HLA association
HLA DR4
Antiphospholipid syndrome Ab
Anti-cardiolipin
Anti-beta2 glycoprotein
Lupus anticoagulant
Autoimmune hepatitis Ab
Anti-smooth muscle antibody
Anti-LKM-1
Anti-SLA (soluble liver antigen)
AIHA Ab
Anti-Rh blood group antigen
Autoimmune thrombocytopenic purpura Ab
Anti-glycoprotein IIb-IIIa
Anti Ib-IX antibody
Churg-Strauss syndrome (eGPA) Ab
p-ANCA
Coeliac disease Abs
Anti-TTG IgA
Anti-Endomysial IgA
Antibody causing congenital heart block in mothers with SLE
Anti-Ro antibody
Dermatitis herpetiformis Ab
Anti-endomysial IgA
Dermatomyositis Ab
Anti-Jo-1 (t-RNA synthetase)
Diffuse cutaneous scleroderma Ab
Anti-Scl70 (anti-topoisomerase)
RNA pol I, II, III
Fibrillarin (nucleolar pattern)
Goodpasture’s syndrome Ab
Anti-GBM
Graves disease Ab
Anti-TSH receptor antibody (stimulatory)
Hashimoto’s thyroiditis Ab
Anti-thyroglobulin
Anti-thyroperoxidase
Limited cutaneous scleroderma (CREST) Ab
Anti-centromere
Microscopic polyangiitis Ab
p-ANCA
Mixed connective tissue disease Ab
Anti-U1RNP (speckled pattern)
Myasthenia gravis Ab
Anti-ACh receptor
Pernicious anaemia Ab
Anti-gastric parietal cell (90%)
Anti-intrinsic factor (50%)
Polymyositis Ab
Anti-Jo-1 (t-RNA synthetase)
Primary biliary cirrhosis Ab
AMA
Rheumatoid arthritis Ab
Anti-CCP Rheumatoid factor (less specific)
Sjogren’s syndrome Ab
Anti-Ro
Anti-La (speckled pattern)
60-70% Rh factor positive
SLE Ab
Anti-dsDNA
Histones, Ro, La, Sm, U1RNP (speckled)
T1DM Ab
Anti-GAD
Pancreatic beta cells
Wegener’s granulomatosis (GPA) Ab
c-ANCA
Polyarteritis nodosa Ab
ANCA
also associated with chronic Hep. B
Give check point inhibitors e.g. CTLA4 to treat what?
Melanoma
Anti CD28 (rheumatoid arthritis)
Abatacept
Anti alpha 4 integrin (MS)
Natalizumab
Anti IL-6 R (RhA)
Tocilizumab
Autosomal recessive form of severe SCID presenting at a few days old. Failure of production of neutrophils, lymphocytes, monocytes/macrophages, and platelets. Failure of stem cells to differentiate along myeloid or lymphoid lineage.
Reticular dysgenesis
Mutation in AK2
Reticular dysgenesis
Specific failure of neutrophil maturation. Autosomal recessive severe congenital neutropenia. HAX1 mutation.
Kostmann syndrome
ELA-2 neutrophil elastase mutation. Autosomal dominant episodic neutrophenia every 4-6 weeks. Failure of neutrophil maturation.
Cyclic neutropenia
CD18 deficiency. Neutrophilia. No pus.
Leukocyte adhesion deficiency
Absent respiratory burst due to deficiency of component of NADPH oxidase. X-linked. NBT test abnormal. Normal neutrophil count. Excessive inflammation and granuloma formation. Lymphadenopathy and hepatosplenomegaly.
Chronic granulomatous disease
Treatment of chronic granulomatous disease
Interferon gamma therapy
IL-12 and INF-gamma deficiency leads to what?
Inability to form granulomas. Susceptible to mycobacteria and salmonella.
Deficiency in early classical pathway (C1/2/4) leads to what?
Increased susceptibility to infection and increased load of self-antigens (SLE)
Factor B/I/P deficiency leads to?
Recurrent infections with encapsulated bacteria
MBL deficiency leads to?
Only causes problems if there is a concurrent cause of immune impairment
Any defect in complement pathway leading to problem with MAC causes?
Increased infections with encapsulated bacteria:
Neisseria meningitidis
Strep. pneumoniae
Haemophilus influenzae
Mutation of gamma chain of IL-2 receptor
X-linked SCID (v. low T cells, normal B cells)
DiGeorge CATCH-22
Cardiac abnormalities Abnormal facies Thymic aplasia (low T cells and IgG/IgA) Cleft palate Hypocalcaemia / hypoparathyroidism 22q11 microdeletion
Absent MHC class II –> profound deficiency of CD4+ T cells and IgG/IgA
Bare lymphocyte syndrome
Immune deficiency associated with sclerosing cholangitis
Bare lymphocyte syndrome
Btk gene mutation. No circulating immunoglobulin after 3 months.
Bruton’s X-linked hypogammaglobulinaemia
Mutation in CD40 ligand gene causes T cell defect and IgM only
HyperIgM syndrome
Low IgG, IgA and IgE due to mutation of MHC III (aberrant class switching)
Common variable immune deficiency, presents in adulthood
Low IgM, raised IgA and IgE
Wiskott-Aldrich Syndrome