Random Immunopath Flashcards
Joint pain and inflammation Fever Rash (salmon-pink) Lymphadenopathy Organomegaly Serositis / Hepatitis
Patient 5yo and more likely female
Systemic Onset JIA or Stills Disease
Chondrocalcinosis
(Calcification of fibro and hyaline cartilage)
= Pseudogout
Atophy
Type 1 IgE mediated allergy (most common allergy) 10% population. - Asthma - Hay Fever - Eczema - Foods - Urticaria and angioedema - Anaphylaxis
Attacks synovial joints
Rheumatoid Arthritis, often progresses to synovial joint destruction. Also targets tendon sheathes and bursae
Anti-bodies to double stranded DNA?
Highly Specific for SLE
Stiffness WORSE in the Morning
Rheumatoid Arthritis
Treatment or hyperacute rejection?
Organ Removal
Issues in Organ Transplant besides rejection
Technical
Cold ischaemia time
Reperfusion injury
Functional status and co-morbidity of recipient
Rejection/Immunosuppression (Infection, Post-transplant-lymphoproliferative disease PTLD (EBV- mediated), Neoplasia - HPV SCC, HHV8 -Kaposi, Lymphoma)
Recurrence (viral, primary FSGS, mesangiocapillary GN, diabetic and IgA nephropathy)
Role of Activated Macrophages in transplant rejection (HVGD)?
Injure graft cells and vasculature.
25% of those with this go blind?
Giant Cell Arthritis
ABO
Most important blood type system (or blood group system) in human blood transfusion. The associated anti-A and anti-B antibodies are usually IgM antibodies, which are produced in the first years of life by sensitization to environmental substances, such as food, bacteria, and viruses.
Erosions
Sign of Joint Destruction in Rheumatoid Arthritis
Steroid Dosing
High (20-40mg p/day)
Medium
Low (250mg given every 24-48 hrs
Classification of Transplant Rejection?
Hyperacute
(Accelerated Acute)
Acute
Chronic
Arthropathy in sacro-iliac and apophysial (facet joints)
Ankylosing spondylitis
Ddx
HLA-B27+ Enteropathic Arthritis
Boutoniere deformities (V at interphalageal joint)
Sign of Joint Destruction in Rheumatoid Arthritis
Scl-70
A poor prognostic indicator for Scleroderma.
Artritis associated with
Abdo pain and melaena
Renal Disease (renal artery affected)
Rash
Polyarteritis Nodosa
Obliterative intimal fibrosis
Glomeruli
Coronary arteries
Vascular damage associated with Chronic Rejection
Tx in Giant Cell Arthritis affecting eye
Corticosteroids can reduce initial inflammation.
Autoimmune reaction resulting in rejection of graft?
Humeral Rejection Type II (Autoantibody) immune response.
Cystic Changes in Bone and Synovium
Osteoarthritis
Arthritis of elderly with heavy male predominance.
Gout
Antibody deficiencies
XLA CVID Hyper-IgM IgA Specific antibody deficiency Transient hypogammaglobulinaemia
Z-deformities (thumb)
Sign of Joint Destruction in Rheumatoid Arthritis
Inflammation & organ dysfunction due to Immune Complex deposition in the vasculature of affected organs
SLE
“Pencil in cup”
Erosive but central not peripheral
Arthritis found in 10-15% of IBD patients
Enteropathic Arthritis
X-linked (young men) Typically presents as a skin infection with +ve organisms (staph aureus, fungi, tc) with deep abscess formation
Chronic Granulomatous Disease
Type of rejection, common (10-30%) in Kidney transplants?
Acute Rejection
Fibrinoid necrosis of vessels and Cortical Infarction in transplant rejection?
Hyperacute Rejection
6wks affecting fewer than 4, mostly larger joints, ANA positive?
Oligoarthritis (Juvenile Idiopathic Arthritis Subtype)
Uurate overproduction due to:
Diet
Enzyme defects (known and unknown)
Decreased excretion
Primary Gout (90%)
Rheumatoid Nodules
Rheumatoid Arthritis
Polyconal Immunoglobulin
Treatment in humoral acute rejection.
On CD4 staining.
Also used = Polygonal Immunoglobulin and Anti-CD20
Non-complement fixing rejection
Accelerated Acute Rejection
Syndrome common in Turkey, Iran and Japan?
Behcet’s Syndrome
Subluxations
Sign of Joint Destruction in Rheumatoid Arthritis
Arthropathy associated with Haemachromatosis?
Pseudogout
Ability of a test to indicate a negative result in the absence
of disease.
Specificity
Joint Effusions
Sign of Joint Destruction in Rheumatoid Arthritis
Role of Cytotoxic T-cells in transplant rejection (HVGD)
Kill cells in the grafted tissue, causing parenchymal and, perhaps more importantly, endothelial cell death (resulting in thrombosis and graft ischemia).
Negatitive birefringment
Gout
Gouty Tophi
Chronic Arthritis Gout
Tests in Septic Arthritis?
Aspirate
Stain
Culture
Paraprotein in blood and/or urine
Multiple Myeloma
Rejection characterised by loss of function w/o fever?
Acute Rejection.
Lip Biopsy in Sjogrens
Periductal and perivascular CD4+ TH cells, B cells, plasma cells , fibrosis
Arthritis usually sparing hips and rest of spine?
Rheumatoid Arthritis
HLA and ABO compatibility min requirement?
Pancreas Transplant
Butterfly rash
Systemic Lupus Erythematous
Patient in upper limbs may have a weak or absent pulse
Takayasu Arteritis
Absence of T cells (
Severe Combined Immunodeficiency (SCID)
Rejection marked by necrotizing vasculitis with thrombosis (when less acute mimics arterioscleotic thickening)
Humeral Acute Rejection (Antibody medicated)
Tx for Polymyalgia rheumatica?
Responsive to steroids
CD11a, 11b, 11c and CD18
Adhesion molecules (Neutrophil Function Disorder)
Histological signs of Polyartritis Nodosa?
Fibrinoid Necrosis
Multiple Thrombosis
ABO Compatibility Essential
HLA as possible
Bone Marrow Transplant
Indications for Glucocorticoids
Significant Acute Inflammation
Types of Chronic GVHD?
Progressive (worst Px)
Interrupted
De novo (best Px)
Rejection Antigens?
MHC (Minor HC antigens account for GVHD in Human Leucocyte Antigen - identical Bone Marrow Transplant)
ABO
Others
Small Vesses Vasculitis?
Microscopic Polyangitis
Wegner’s Granulomatosis
Churg-Straus
Henoch-Schonlein Purpura
Investigation for Anaphylaxis?
Mast cell tryptase Demonstration of mast cell degranulation Elevated levels seen from 1-12 hrs after rxn 90% specific Sensitivity less good
Usually IgE-mediated
Food allergy
Other stimuli not excluded
ELISA meaning?
Enzyme Linked ImmunoSorbant Assay
Chondrocyte Proliferation?
Osteoarthritis
Arthritis affecting articular cartilage, with a periarticular bone response
Osteoarthritis
HLAB4 is a haplotype of this arthritis.
Rheumatoid Arthritis
Anti-nuclear antibody (ANA) Anti-dsDNA antibody ENA antibodies Anti-RBC antibody Anti-cardiolipin & lupus anticoagulant
All auto-antibodies of Systemic Lupus Erythematous
DR4 and DR1
Rheumatoid Arthritis
ANA patterns
Homogenous
Speckled
Centromere
Nucleolar
Autoimmune form of arthritis
Rheumatoid Arthritis
Ulnar deviation (fingers towards little finger)
Sign of Joint Destruction in Rheumatoid Arthritis
Detection of Anti-Nuclear Antibodies?
Indirect Immunofluoresence
Aldosterone
Main Natural Glucocorticoid
Recurrent infections – RTIs (lungs & ears chronic OM)
Meningitis and septic arthritis
Agammaglobinaemia.
T-Cell Mediated Rejection?
Cellular Rejection (as opposed to humeral)
Cytotoxic T-Cells \+ Cytokine Sectreting CD4+ T-Cells \+ Activated Microphages.
Vasculitis
Rheumatoid Arthritis
MPO-ANCA
Anti-myeloperoxidase ANCA
=Microscopic PolyAngiitis & =Churg-Strauss Δ - necrotising vasculitis - asthma - allergic rhinitis - pulmonary infiltrates - increased circulating eosinophils - necrotizing granulomas (extrvascular)
No HLA, but ABO compatibility required?
Cardiac and Liver transplant
Process which has reduced the incidence of hyperacute transplant rejection?
Cross Matching
Type 2 Allergy
Autoantibody
RNP
100% Mixed Connective Tissue Disease
Monitoring of query “Hyperacute rejection’?
U/S Doppler ofr BF or Duplex
Squamous cell carinoma a side effect of which type of drug?
Immunosuppressants
Type of arthritis that increase in prevalence with increase in latitute?
Rheumatoid Arthritis
SLE affects who?
Females x9 more
20-30’s
60% Concordance in Twins.
Low Risk CMV group in BMT
CMV- Recipient, CMV- Donor
Sequence for BMT Transplantation
- Matchining (fully matched sibling can be used whole)
- Viral Status (esp. CMV)
- Conditioning of Recipient (eliminate residual immune system. Note: not required in Sever Combined Immune Deficiency (SCID).
- Immunosuppression
- Growth factor support.
- Supportive blood products (CMV-)
Difference between direct and indirect cellular rejection?
Own (indirect) versus donor (direct) antigen presenting cells (APC’s) which are presenting the MHC (always from donor).
Caplans Syndrome
Rheumatoid arthritis (RA) and pneumoconiosis combination.
Manifests as intrapulmonary nodules, which appear homogenous and well-defined on chest X-Ray
ALG (Anti-lymphocyte globulin)
ALG is used as a treatment for vascular acute transplant rejection. Along with ATG
- Upper airways (necrotising granulomas)
- Necrotising granulomatous vasculitis (small-medium vessels)
- Necrotising glomerulonephritis
Wegners Granulomatosis
Genital ulcers
Eye: Uveitis (anterior or posterior) Retinal vasculitis
Skin: Erythema nodosum, Pseudofolliculitis, Papulopustular lesions
Pathergy
Minor skin injury precipitates pustules in a couple of days
±Constitutional symptoms
Behcet’s Syndrome
Chrystal Arthritides
Pseudogout
ATG (Anti-Thymocyte Globulin)
Anti-thymocyte globulin is used in the treatment of vascular acute rejection. Along with ALG.
Podgara
Acute Arthritis Gout
Test for paraproteins?
Electrophoresis
Risk lymphoma 1.16 (MALTOMA)
Sjogrens
Asymmetrical arthritis of lower limb
Enteropathic Arthritis
Xenograft
From animal e.g. Pig heart valves
Pain on movement of joint
Rheumatoid Arthritis
HLA-B27
95% w/Ankylosing spondylitis are HLA-B27+
8% of Caucasian population = HLA-B27+
80% w/Reactive Arth/Reiters are HLA-B27+
Enteropathic Arthritis w/sacroiliitis or spondylitis
Psoriatic Arthritis
The Secondary Osteoarthritis.
Metabolic – Gout &
Pseudogout (Chondrocalcinosis)
Infectious / Septic Arthrits
Rejection in
Acute GVHD
HLA-B8
Sjogrens
Treatment for chronic granulomatous disease?
Prophylaxis (co-trimoxasole, itraconasole)
BMT
Transplant rejection over 1-5 days
Accelerated Acute Rejection
Tightening of skin around the mouth
Portal system of the liver
White out lung disease (acute vascular information)
GI fibrosis and dysmotilty
Chronic GVHD
Anti lymphocyte Globulins
Immunosuppressant
Arthritis within weeks after shigella, salmonella, yersinia, campylobacter or chlamydia.
Reactive Arthritis/Reiter Syndrome
Common causative organisms in Septic Arthritis?
Haemophilus influenzaepredominates in children under age 2 years,
Staph. Aureus:older children and adults,
Gonococcus: young adulthood. mainly in sexually active women
Individuals with sickle cell disease are prone to infection withSalmonellaat any age.
Gram negative bacilli (elderly),
Kaposi sarcoma a s/e of what drugs? Where else seen?
Immunosuppressants/HIV progression to AID’s
Degenerative arthritis
Osteoarthritis
Mortality in BMT patients?
20-40%
Umbilical Cord Blood
Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders.
Dx of Multiple Myeloma
Monoclonal expansion of paraprotein secreting plasma cells in bone marrow
IgG 60% of cases
IgA 20% of cases
Light chains alone 15-20% of cases
> 20% Abnormal looking BM plasma cells
Multiple Myeloma
COL2A1 gene
Familial Osteoarthritis
Local factors affecting loading and wear (point loading) “Secondary Osteoarthritis” Injury Obesity Instability Hypermobility Joint dysplasia Neuropathy
Secondary Osteoarthritis
Large cause of mortality in gout?
Gouty nephropathy (20% of gout mortality)
IgA immune complexes deposited in mesangium.
IgA nephropathy.
Pathogenesis of Gout
Hyperuricemia
Urate precipitates in joints forming crystals
- Activation of complement and kinen system
Neutrophil chemotaxis
Release LTB4, prostaglandins and free radicals causes tissue inflamm.
Neutrophils phagocytose crystals, causing lysis of neutrophils .
Release of lysosomal enzymes leads to tissue inflaCammation. - Phagocytosis by macrophages
Leads to release of IL-1Beta and other cytokines in joint (resulting in further neutrophil chemotaxis)
Release of proteases leads to tissue inflammation.
“telescopic fingers” “whittling”
Arthritis mutilans due to osteolysis seen in 5% of Psoriatic Arthritis cases
FcR-bearing cells (T-Cells – primarily Cytotoxic)
Accelerated Acute Rejection
BMT graft sources
Allogenic (Match sibling or unrelated doner)
Autologous
PR3-ANCA
Anti-proteinase-3 ANCA = Wegener’s Granulomatosis - Upper airways (necrotising granulomas) - Necrotising granulomatous vasculitis (small-medium vessels) - Necrotising glomerulonephritis
Seronegative destruction of articular cartilage and bony ankylosis
Ankylosing spondylitis.
Usually affect sacro-iliac and apophysial joints
Anti-GBM antibody
Goodpastures
Suspected mechanism behind chronic rejection?
Recipient cells present MHC from the recipient organs
Lenght of post BMT neutropenia?
Should lift be 21 days
Should be excluded first in Dx of pseudogout?
Septic Arthritis
Iritis and conjunctivitis
Psoriatic Arthritis
RF+
Polyarthritis (Juvenile Idiopathic Arthritis Subtype)
Ddx
10% of Psoriatic Arthritis
Sjogrens (75%)
HLA-DR3
Sjogrens