Immunopathology Associations Flashcards
(337 cards)
1
Q
Attacks synovial joints
A
Rheumatoid Arthritis, often progresses to synovial joint destruction. Also targets tendon sheathes and bursae
2
Q
Autoimmune form of arthritis
A
Rheumatoid Arthritis
3
Q
Arthritis that peaks age 40, but can become symp in 40’s
A
Rheumatoid Arthritis
4
Q
Arthritis, more common in females than males
A
Rheumatoid Arthritis
5
Q
HLAB4 is a haplotype of this arthritis.
A
Rheumatoid Arthritis
6
Q
Type of arthritis that increase in prevalence with increase in latitute?
A
Rheumatoid Arthritis
7
Q
Histological Pathogenesis of Rheumatoid Arthritis.
A
- Synovial edema and sparse mononuclear infiltrate.
- Synovial aggregates of mononuclear cells, CD4+ THELPER Cells, Plasma cells, Dendritic cells, Macrophages
- Synovial hyperplasia with villous change
- Increased synovial vascularity
- Organising fibrin on synovial surface and neurtophils on synovial surface and in joint space.
- Osteoclast activation = osteoporosis, junta-articular erosions, sub-chondral cysts.
- Mass of boggy inflammed synovium PANNUS, can erode cartilage, bone and ligament.
- Joint destroyed. Loss of articular cartilage. Fibrous ankylosis or Unstable
8
Q
Mass of boggy inflammed synovium that can erode cartilage, known as what? Seen in What?
A
PANNUS
Rheumatoid Arthritis
9
Q
Signs and symptoms of PANNUS/Rheumatoid Arth?
A
(4 basic signs of inflammation)
- Calor
- Rubor (
- Tumour (swelling)
- Dolar (pain)
10
Q
Common site to observe synovial joint destruction
A
Metacarpal/interphalangeal joints
11
Q
HLA-DRB1
A
Rheumatoid Arthritis.
12
Q
TH17
A
Neutrophil recruitment – Rheumatoid Arthritis
13
Q
TH1
A
Interferon Gamma (y) – Rheumatoid Arthritis
14
Q
Cartilage Matric Metalloproteases
A
Rheumatoid Arthritis
15
Q
Immune Complexes
A
Rheumatoid Arthritis
16
Q
RANKL
A
Rheumatoid Arthritis
17
Q
TNF
A
Rheumatoid Arthritis
18
Q
Stiffness WORSE in the Morning
A
Rheumatoid Arthritis
19
Q
Pain on movement of joint
A
Rheumatoid Arthritis
20
Q
Small non-weight bearing joints (Hands and Feet, C-Spine)
A
Rheumatoid Arthritis
21
Q
Important test pre-intubation
A
Sign of RA on the Neck = X-Ray, Lateral and an AP. Shows narrowing, bony erosions etc.
22
Q
Treatment for Rheumatoid arthritis?
A
Total Joint Replacement
Joint Fusion.
23
Q
Arthritis usually sparing hips and rest of spine?
A
Rheumatoid Arthritis
24
Q
Symmetrical arthritis
A
Rheumatoid Arthritis
25
Z-deformities (thumb)
Sign of Joint Destruction in Rheumatoid Arthritis
26
Boutoniere deformities (V at interphalageal joint)
Sign of Joint Destruction in Rheumatoid Arthritis
27
Swan neck deformities
Sign of Joint Destruction in Rheumatoid Arthritis
28
Ulnar deviation (fingers towards little finger)
Sign of Joint Destruction in Rheumatoid Arthritis
29
Volar subluxation (enlargement at knuckles caused by tendon slip)
Sign of Joint Destruction in Rheumatoid Arthritis
30
Joint Effusions
Sign of Joint Destruction in Rheumatoid Arthritis
31
Juxta-articular osteopaenia
Sign of Joint Destruction in Rheumatoid Arthritis
32
Erosions
Sign of Joint Destruction in Rheumatoid Arthritis
33
Joint Space Narrowing
Sign of Joint Destruction in Rheumatoid Arthritis
34
Subluxations
Sign of Joint Destruction in Rheumatoid Arthritis
35
Secondary Amyloidosis
Protein Misfolding. Seen in...
| Rheumatoid Arthritis.
36
Serosistitis
Inflammation of the serosa. Seen in...
| Rheumatoid Arthritis
37
Caplans Syndrome
Rheumatoid arthritis (RA) and pneumoconiosis combination.
Manifests as intrapulmonary nodules, which appear homogenous and well-defined on chest X-Ray
38
Felty's Syndrome
Combination of heumatoid arthritis, splenomegaly and neutropenia.
39
Sicca's (Sjogrens) Syndrome
Chronic autoimmune disease in which the body's white blood cells destroy the exocrine glands, specifically the salivary and lacrimal glands, that produce saliva and tears, respectively.[2] The immune-mediated attack on the salivary and lacrimal glands leads to the development of xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes), which takes place in association with lymphocytic infiltration of the glands.
40
Vasculitis
Rheumatoid Arthritis
41
Pneumonitis
Rheumatoid Arthritis
42
Rheumatoid Nodules
Rheumatoid Arthritis
43
Serology of Rheumatoid Arthritis
1. Rheumatoid factor (80%)
non-specific
Antibodies (usually IgM) against IgG Fc portion
Marker for activity
2. APCA (anti-citrullinated peptide antibodies)
Specific for RA
44
Rheumatoid Factor
Seen in 80% of Rheumatoid Arthritis
non-specific
Antibodies (usually IgM) against IgG Fc portion
Marker for activity
45
Anti-Citrullinated Peptide Antibodies (ACPA) (AKA ACCP)
Rheumatoid Arthritis (Specific)
46
ACR/EULAR 2010 Criteria
```
Rheumatoid Arthritis
Points for:
Joint Involvement
Serology
Acute phase reactants
Duration of symptoms
```
47
Degenerative arthritis
Osteoarthritis
48
Arthritis affecting articular cartilage, with a periarticular bone response
Osteoarthritis
49
Mechanical degradation of joints
Osteoarthritis
50
Arthritis associated with old age?
Osteoarthritis
51
COL2A1 gene
Familial Osteoarthritis
52
WNT signalling, Prostaglandin pathways
Osteoarthritis
53
```
Local factors affecting loading and wear (point loading)
“Secondary Osteoarthritis”
Injury
Obesity
Instability
Hypermobility
Joint dysplasia
Neuropathy
```
Secondary Osteoarthritis
54
Chondrocyte Proliferation?
Osteoarthritis
55
Stages of osteoarthritis?
1. Chondrocyte Proliferation
2. Mediator Release
3. Cartilage Remodelling
4. Secondary Changes in Bone and Synovium
(Cystic Changes)
5. Loss of cartilage with subchondral bony change
56
Loss of cartilage with subchondral bony change
Osteoarthritis
57
Cystic Changes in Bone and Synovium
Osteoarthritis
58
Arthritis in PIP's, 1sr MCP and 1st MTP joints
Osteoarthritis
59
Arthritis in Lumbar and Cervical Spine
Osteoarthritis
60
Deep, achy pain
Worsens with use
Short-lived morning stiffness
Osteoarthritis
61
Crepitus
Osteoarthritis
62
Decreased range of movement
Osteoarthritis
63
Subchondral Sclerosis
Osteoarthritis
64
Subchondral Cysts
Osteoarthritis
65
The Secondary Osteoarthritis.
Metabolic – Gout &
Pseudogout (Chondrocalcinosis)
Infectious / Septic Arthrits
66
The Seronegative immune mediated joint disorders
Ankylosing spondylitis
Reactive arthritis/Reiter syndrome
Enteropathic arthritis
Psoriatic arthritis
67
Joint disorder common in 6wks
Juvenile Idiopathic Arthritis
68
6wks affecting fewer than 4, mostly larger joints, ANA positive?
Oligoarthritis (Juvenile Idiopathic Arthritis Subtype)
69
6wks affecting more than 4, mostly smaller joints, RF+ positive? With poorer prognosis
Polyarthritis (Juvenile Idiopathic Arthritis Subtype)
70
ANA
Oligoarthritis (Juvenile Idiopathic Arthritis Subtype)
71
RF+
Polyarthritis (Juvenile Idiopathic Arthritis Subtype)
Ddx
10% of Psoriatic Arthritis
Sjogrens (75%)
72
Stills Disease
Systemic Onset JIA
73
Joint pain in 5yo
```
Systemic Onset JIA. Also...
Fever
Rash (salmon-pink)
Lymphadenopathy
Organomegaly
Serositis / Hepatitis
```
74
```
Joint pain and inflammation
Fever
Rash (salmon-pink)
Lymphadenopathy
Organomegaly
Serositis / Hepatitis
```
Patient 5yo and more likely female
Systemic Onset JIA or Stills Disease
75
Seronegative destruction of articular cartilage and bony ankylosis
Ankylosing spondylitis.
| Usually affect sacro-iliac and apophysial joints
76
Arthropathy in sacro-iliac and apophysial (facet joints)
Ankylosing spondylitis
Ddx
HLA-B27+ Enteropathic Arthritis
77
Seronegative arthritis more common in males, average more common in mid-20's
Ankylosing spondylitis
78
Question mark spine
Ankylosing spondylitis
79
Schober's test (limited flexion (
Ankylosing spondylitis
80
Uveitis
Ankylosing spondylitis
81
Aortitis
Ankylosing spondylitis
82
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
83
```
Arthritis (sausage finger, bony spurs)
+
Nongonococcal urethritis/cervicitis (+/- circinate balanitis)
+
Conjunctivitis
```
Reactive Arthritis/Reiter Syndrome
Also,
+/- oral ulceration, heart block, aortic regurgition
50% is chronic and resembles Ankylosing Spondylitis.
84
Arthritis within weeks after shigella, salmonella, yersinia, campylobacter or chlamydia.
Reactive Arthritis/Reiter Syndrome
85
Arthritis of mostly men 20-40
Reactive Arthritis/Reiter Syndrome
Or
Ankylosing Spondylitis
```
Ddx
Possible Rheumatoid (early)
```
86
Less severe symptoms that reiter but nonetheless following infection?
Enteropathic Arthritis
87
Arthritis found in 10-15% of IBD patients
Enteropathic Arthritis
88
Asymmetrical arthritis of lower limb
Enteropathic Arthritis
89
Seronegative (in 90%) arthritis associated with psoriasis 20-40yo?
Psoriatic Arthritis (10% RF+)
90
HLA-CW6
Psoriatic Arthritis
91
Arthritis usually DIP, dactylitis, sausage finger/TOE 33%.
Also sometimes ankles, knees, hips, SI and facet joints
Asymetric, Histo resembling RA but not as destr.
Psoriatic Arthritis
92
“telescopic fingers” “whittling”
Arthritis mutilans due to osteolysis seen in 5% of Psoriatic Arthritis cases
93
“Pencil in cup”
Erosive but central not peripheral
94
Iritis and conjunctivitis
Psoriatic Arthritis
95
Hyperuricaemia
Gout (w/intraarticular sodium urate chrytals)
10% have hyperuricaemia, only 0.5% have gout
96
Intraarticular sodium urate chrystals
Gout (w/hyperuricaemia)
97
Arthritis of elderly with heavy male predominance.
Gout
98
Pathogenesis of Gout
Hyperuricemia
Urate precipitates in joints forming crystals
1. 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.
2. 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.
99
Podgara
Acute Arthritis Gout
100
Gouty Tophi
Chronic Arthritis Gout
101
Large cause of mortality in gout?
Gouty nephropathy (20% of gout mortality)
102
Uurate overproduction due to:
Diet
Enzyme defects (known and unknown)
Decreased excretion
Primary Gout (90%)
103
Overproduction of Urate
- Increased cell turnover
- Inborn errors of metabolism
Reduced excretion
-Chronic renal failure
Secondary Gout (10%)
104
Chrystal Arthritides
Pseudogout
105
Calcium pyrophosphate dihydrate deposition disease
Pseudogout
106
Acute pain and swelling in knee, wrist or shoulder
Pseudogout
107
Chondrocalcinosis
(Calcification of fibro and hyaline cartilage)
| = Pseudogout
108
Calcification of fibro and hyaline cartilage
Pseudogout
109
Low Phosphate
Pseudogout
110
Low Magnesium
Pseudogout
111
Increase PTH
Pseudogout
112
Arthropathy associated with Wilsons disease?
Pseudogout
113
Arthropathy associated with Haemachromatosis?
Pseudogout
114
Arthropathy associated with Alkaptonuria disease?
Pseudogout
115
Weakly positively birefringent rhomboid crystals on polarisation.
May be cloudy and associated with fever and ↑ peripheral WCC
Result from joint aspirate
| =Pseudogout
116
Treatment for Pseudogout
Supportive
117
Should be excluded first in Dx of pseudogout?
Septic Arthritis
118
Negatitive birefringment
Gout
119
Hot, Red, one joint?
Septic Arthritis
120
Routes to septic arthritis?
Direct inoculation through injury
Direct spread from adjacent infection
Haematogenous spread
121
Common causative organisms in Septic Arthritis?
Haemophilus influenzae predominates 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 with Salmonella at any age.
Gram negative bacilli (elderly),
122
Tests in Septic Arthritis?
Aspirate
Stain
Culture
123
HLA-B8
Sjogrens
124
HLA-DR3
Sjogrens
125
Sjograns w/o RA?
Primary Sjogrens
126
Salivary gland enlargement F>M
Sjogrens
127
Risk lymphoma 1.16 (MALTOMA)
Sjogrens
128
Investigations in Sjogrens?
Lip biopsy
129
Lip Biopsy in Sjogrens
Periductal and perivascular CD4+ TH cells, B cells, plasma cells , fibrosis
130
Anti-Ro
Sjogrens (90%) also RF (75%)
131
Schirmer Tear Test
Sjogrens
132
Syndrome common in Turkey, Iran and Japan?
Behcet's Syndrome
133
HLA-B51
Behcet's Syndrome
134
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
135
Anti-La
Sjogrens (60-90%)
| SLE (10-15%)
136
MPO-ANCA
Anti-myeloperoxidase ANCA
```
=Microscopic PolyAngiitis
&
=Churg-Strauss Δ
- necrotising vasculitis
- asthma
- allergic rhinitis
- pulmonary infiltrates
- increased circulating eosinophils
- necrotizing granulomas (extrvascular)
```
137
- necrotising vasculitis
- asthma
- allergic rhinitis
- pulmonary infiltrates
- increased circulating eosinophils
- necrotizing granulomas (extrvascular)
Churg Strauss Syndrome
138
PR3-ANCA
```
Anti-proteinase-3 ANCA
= Wegener’s Granulomatosis
- Upper airways (necrotising granulomas)
- Necrotising granulomatous vasculitis (small-medium vessels)
- Necrotising glomerulonephritis
```
139
- Upper airways (necrotising granulomas)
- Necrotising granulomatous vasculitis (small-medium vessels)
- Necrotising glomerulonephritis
Wegners Granulomatosis
140
Autologous
Self Organ Donation (graft etc)
141
Syngeneic
Monozygotic (identical) siblings
142
Allogeneic
Living or Cadaveric (Another genetically different person donor)
143
Umbilical Cord Blood
Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders.
144
Xenograft
From animal e.g. Pig heart valves
145
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)
146
Rate of 5-10y graft survival?
(80%)
147
Rate of 10-20y graft survival?
(50%)
148
Definition of transplant rejection?
Aka HOST versus graft
“A process whereby the transplant recipient’s immune system recognizes the graft as foreign and attacks it with potential adverse effects on its viability and function”
149
Rejection Antigens?
MHC (Minor HC antigens account for GVHD in Human Leucocyte Antigen - identical Bone Marrow Transplant)
ABO
Others
150
MHC
Major Histocompatability Complex
Mediated Graft Versus Host disease in HLV identical BMT
Seen in Hyperacute rejection (MHC1)
151
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.
152
No HLA, but ABO compatibility required?
Cardiac and Liver transplant
153
HLA and ABO compatibility min requirement?
Pancreas Transplant
154
```
Extensively matched
ABO (ABO mismatched are possible)
+
HLA (mostly DR)
+
X-matched for preformed antibodies
```
Kidney Transplant
155
ABO Compatibility Essential
| HLA as possible
Bone Marrow Transplant
156
T-Cell Mediated Rejection?
Cellular Rejection (as opposed to humeral)
```
Cytotoxic T-Cells
+
Cytokine Sectreting CD4+ T-Cells
+
Activated Microphages.
```
157
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).
158
Role of Cytokine Secreting CD4+ T-Cells in transplant rejection (HVGD)?
Trigger DTH (delayed type hypersensitivity), with increased vascular permeability and local accumulation of mononuclear cells (lymphocytes and macrophages).
159
Role of Activated Macrophages in transplant rejection (HVGD)?
Injure graft cells and vasculature.
160
DTH
Trigger DTH (delayed type hypersensitivity), with increased vascular permeability and local accumulation of mononuclear cells (lymphocytes and macrophages).
161
Autoimmune reaction resulting in rejection of graft?
```
Humeral Rejection
Type II (Autoantibody) immune response.
```
162
Classification of Transplant Rejection?
Hyperacute
(Accelerated Acute)
Acute
Chronic
163
Cyanotic, mottled and flacid graft on removal of vascular clamps in Operating Room?
Hyperacute Rejection
164
Rejection involving complement fixing
Hyperacute Rejection
165
Graft rejection in less
Hyperacute Rejection
166
Treatment or hyperacute rejection?
Organ Removal
167
Rejection involving preformed antibodies? Name the antibody types?
MHC 1 or ABO, mothers, previous transfusions and transplants)
168
Fibrinoid necrosis of vessels and Cortical Infarction in transplant rejection?
Hyperacute Rejection
169
Process which has reduced the incidence of hyperacute transplant rejection?
Cross Matching
170
Monitoring of query “Hyperacute rejection'?
U/S Doppler ofr BF or Duplex
171
Transplant rejection over 1-5 days
Accelerated Acute Rejection
172
Non-complement fixing rejection
Accelerated Acute Rejection
173
FcR-bearing cells (T-Cells – primarily Cytotoxic)
Accelerated Acute Rejection
174
Rejection, can be humeral or cell mediated, but is more commonly cell mediated?
Accelerated Acute Rejection
175
Rejection that often relapses?
Accelerated Acute Rejection
176
Treatment for Accelerated Acute Rejection?
Immosuppression, but only partially effective.
| Transplant removal often required.
177
Rejection between 6-90 days?
Acute Rejection
178
Type of rejection, common (10-30%) in Kidney transplants?
Acute Rejection
179
Anti-CD20
Treatment used in humoral acute rejection.
On CD4 staining.
Also seen = Polyconal Immunoglobulin, Plasmapharesis
180
Plamaphaesis
Treatment in humoral acute rejection. On CD4 staining. Also used = Plasmapharesis and Anti-CD20
181
Polyconal Immunoglobulin
Treatment in humoral acute rejection.
On CD4 staining.
Also used = Polygonal Immunoglobulin and Anti-CD20
182
ATG (Anti-Thymocyte Globulin)
Anti-thymocyte globulin is used in the treatment of vascular acute rejection. Along with ALG.
183
ALG (Anti-lymphocyte globulin)
ALG is used as a treatment for vascular acute transplant rejection. Along with ATG
184
Treatment for acute transplant rejection?
```
Cellular
Steroids
Vascular
ATG, ALG
Humoral
C4 staining
Polyconal immunoglobulin, plasmapharesis, antiCD20
```
185
Rejection characterised by loss of function w/o fever?
Acute Rejection.
186
Pathogenesis an Tx targets of Acute Rejection?
Endothelium is main target of pathology
CD4+ and CD8+ infiltrate (glomerular and tubular damage and endothelitis)
Necrosis
Heart: Lymphocyte infiltrate and myocyte damage
Vascular response may be subacute proliferation and fibrosis
Responds to aggressive immunosuppression (particularly anti-T cell strategies)
Progression to chronic rejection common
187
Rejection marked by an interstitial mononuclear cell infiltrate with associated edema and parenchymal injury,
Cellular Acute Rejection
188
Rejection marked by necrotizing vasculitis with thrombosis (when less acute mimics arterioscleotic thickening)
Humeral Acute Rejection (Antibody medicated)
189
Rejection over months/years
Chronic Rejection
190
Obliterative intimal fibrosis
Glomeruli
Coronary arteries
Vascular damage associated with Chronic Rejection
191
```
Interstitial fibrosis
Tubular atrophy
Vanishing bile duct syndrome
Bronchiolitis obliterans
Gross scarring and shrinkage
```
Chronic Rejection
192
Relatively refractory with progressive loss of graft function
Chronic Rejection
193
Why are chronic rejections the most common?
Immunosuppresents so good it drags rejection out
194
Suspected mechanism behind chronic rejection?
Recipient cells present MHC from the recipient organs
195
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).
196
Indirect cellular rejection
Usually chronic rejection
197
Methods for improving graft survival?
1. Better Matching
| 2. Immunosuppression
198
Better HLA matching improves Graft survival?
Yes but....
As drugs for immunosuppression have improved, HLA matching is not even attempted in some situations, such as heart, lung, and liver transplantation; in these cases, the recipient often needs a transplant urgently.
199
Cyclosporine (FK506)
Immunosuppressant
200
Anti lymphocyte Globulins
Immunosuppressant
201
Monoclonal Antibodies (e.g. Monoclonal Anti-CD3)
Immunosuppressant
202
Squamous cell carinoma a side effect of which type of drug?
Immunosuppressants
203
Kaposi sarcoma a s/e of what drugs? Where else seen?
Immunosuppressants/HIV progression to AID's
204
Lymphomas as s/e?
Immunosuppressants
205
Presensitisation?
Now Countered by cross-matching
Irradiated to leucocyte deplete
Questionable increase in tolerance
206
Tx for Aplasia/neoplasias/Herediatary immunodeficineies or metablic abnormalities?
Bone Marrow Transplantation
207
Mortality in BMT patients?
20-40%
208
BMT graft sources
Allogenic (Match sibling or unrelated doner)
| Autologous
209
BMT graft types
Bone Marrow
Peripheral Stem Cells (mat. T-cells)
Cord Stem Cells
210
Graft manipulation for BMT
1. T-Cell Depletion (less GVHD, Less successful engraftment, Less graft v tumour)
2. Stem Cell (CD34+) Enrichment
211
Sequence for BMT Transplantation
1. Matchining (fully matched sibling can be used whole)
2. Viral Status (esp. CMV)
3. Conditioning of Recipient (eliminate residual immune system. Note: not required in Sever Combined Immune Deficiency (SCID).
4. Immunosuppression
5. Growth factor support.
6. Supportive blood products (CMV-)
212
Low Risk CMV group in BMT
CMV- Recipient, CMV- Donor
213
High Risk CMV group in BMT
CMV+ Recipient
| w/wo CMV+ Donor
214
Lenght of post BMT neutropenia?
Should lift be 21 days
215
Time to NK cells post BMT?
1 month
216
Time to T-Cells post BMT?
Depends on T-Cell
1-24 for most.
Some never return.
Depends too on immunosuppression
217
Time to B-Cells post BMT?
Slow production for 1st 3months
If rapid in 1st 3mts then suspect autologous reconstitution or lymphoproliferative disease.
Plateaus out at between 6-9 months
218
IgM, IgG, IgA normalisation post BMT?
6-24 months
219
Vaccination post BMT?
Follow guidelines
| No BMT.
220
Immunocompetent donor T-cells recognize a mismatch with recipient HLA and initiate an immune response against an immunologically vulnerable host
Graft Versus Host Disease (GVHD)
221
Rate of GVHD in BMT?
30-50%
222
Transplants associated with GVHD?
BMT (30-50%)
Blood Transfusion
Solid Organs, commonly LIVER (immune organ CD4+8 cells, transplanted a lot) (others =occasionally)
223
Minor histocompatibility antigens
Non-MHC encoded polymorphisms
Cytokine polymorphisms
Mechanism of GVHD which avoid “Matching”
Occasionally seen in autologous transplants die t re-emergence of autoreactive t-cells
224
Rejection in
Acute GVHD
225
Maculopapular rash +
| Hepatosplenomegaly
Acute GVHD
226
Treatment for Acute GVHD?
Aggressive and early
| Steroids + Anti-T-Cell agents + Anti-TNFalpha
227
Types of Chronic GVHD?
Progressive (worst Px)
Interrupted
De novo (best Px)
228
Similar in appearance to systemic scleosis and Sjogrens?
Chronic GVHD
229
Tightening of skin around the mouth
Portal system of the liver
White out lung disease (acute vascular information)
GI fibrosis and dysmotilty
Chronic GVHD
230
Granulomatous arteritis of the aorta and larger vessels with a predilection for the extracranial branches of the carotids
Giant Cell Arthritis
231
Older person
| Unilateral Headache, facial pain and scalp tenderness.
Giant Cell Arthritis
232
Arteritis far more common in the elderly (>50) and affect F>M, 2:1?
Giant Cell Arthritis
233
Commonest primary systemic vasculitis
Giant Cell Arthritis
234
ESR adjusted for age and CRP if this condition is suspected.
Giant Cell Arthritis
235
25% of those with this go blind?
Giant Cell Arthritis
236
Tx in Giant Cell Arthritis affecting eye
Corticosteroids can reduce initial inflammation.
237
Skip Lesions
| Often associated with polymyalgia rheumatica
Giant Cell Arthritis
238
```
Bilateral neck, shoulder and low back
pain and stiffness.
Worse in the morning
Malaise, tiredness, weight loss, depression and fever.
Elevated ESR and CRP.
```
Polymyalgia Rheumatica
239
Tx for Polymyalgia rheumatica?
Responsive to steroids
240
HLA-DRB1*04
Polymyalgia Rheumatica
241
HLA-DRB1*01
Polymyalgia Rheumatica
242
Arthritis with temporal relationship to outbreaks of...
Parainfluenza
Parvovirus B19
Mycoplasma
Chlamydia
Polymyalgia Rheumatica
243
Association between GCA and polymyalgia rheumatica?
50% of patients with Giant Cell Arteritis have symptoms of PMR and up to 20% of PMR patients have biopsy findings of GCA
244
Pulseless Syndrome
Takayasu Arteritis
245
Patient in upper limbs may have a weak or absent pulse
Takayasu Arteritis
246
Granulomatous thickening of the aortic arch, which primarily affects the brachial artery yeilding a pulsless upper limb
Takayasu Arteritis
247
Arthritis affecting young adults?
Polyarteritis Nodosa
248
Artritis affecting mostly small and medium arteries?
Polyarteritis Nodosa
249
Artritis associated with
Abdo pain and melaena
Renal Disease (renal artery affected)
Rash
Polyarteritis Nodosa
250
Virus associated with Polyartritis Nodosa?
Hepatitis B
251
Necrotising Vasculitis?
Polyartrirs Nodosa
252
Histological signs of Polyartritis Nodosa?
Fibrinoid Necrosis
| Multiple Thrombosis
253
Erythema of hands and fee (cutaneous) and of eyes and mouth (muco) t, e in children?
Query Kawasaki disease.
254
Artritis affecting large, small and medium arteries in children?
Kawakaski
255
Sex affected more by kawasaki?
Male
256
Lymph and Cardiac Signs of Kawasaki Disease?
Lymph = Cervical Lymphadenopathy
| Coronary Arteries = Aneurysm and MI
257
Anti-endothelial and smooth muscle antibodies
Kawakaski
258
Young men
Buerger’s Disease(Thromboangitis Obliteran)
259
Small Vesses Vasculitis?
Microscopic Polyangitis
Wegner’s Granulomatosis
Churg-Straus
Henoch-Schonlein Purpura
260
P-ANCA, purpura, lungs, kidneys, cvs, git, necrotizing glomerular nephritis, exogenous antigens from drugs , blood and infections.
Microscopic Polyangitis
261
Triad:
Renal Disease
Chronic Sinusitis
Pneumonitis
ANCA+
Wegner’s Granulomatosis (Tx = Rapid Immunosup)
262
Typically affects vessels of respiratory tract, strongly associated with asthma, eosinophilia and pulmonary infiltrates. May also have GI Sx (e.g. colitis, bleeding) +/- cardiac +/- peripheral neuropathy Sx’s.
P-ANCA+ and IgE
Churg-Straus Syndrome (Tx = Glucocortiocids +Support)
263
Small vessel IgA & immune complex mediated vasculits often following upper-RTI in young children
Giveaway is lesions on the buttocks and legs
Henoch-Schonlein Purpura
264
Ability of a test to indicate a negative result in the absence
of disease.
Specificity
265
Ability of a test to indicate a positive result in the presence
of disease.
Sensitivity
266
Immune complex mediated disease affecting any organ with diverse manifestations and variable prognosis?
Systemic Lupus Erythematous
267
SLE affects who?
Females x9 more
20-30's
60% Concordance in Twins.
268
Varients of SLE limited only to the skin?
Discoid lupus erythematosus
| Subacute cutaneous lupus
269
Butterfly rash
Systemic Lupus Erythematous
270
Arthralgia and arthritis with skin and haematological abnormalities?
Systemic Lupus Erythematous
271
Haematological features of SLE?
Immune thrombocytopaenia
Haemolytic anaemia
Autoimmune neutropaenia
272
```
Anti-nuclear antibody (ANA)
Anti-dsDNA antibody
ENA antibodies
Anti-RBC antibody
Anti-cardiolipin & lupus anticoagulant
```
All auto-antibodies of Systemic Lupus Erythematous
273
Inflammation & organ dysfunction due to Immune Complex deposition in the vasculature of affected organs
SLE
274
Dx for SLE?
Clinical Hx & examination
Urinalysis & urine microscopy
Assess function of potentially involved organs.
Autoantibodies (Indirect immunofluoresence)
DIFF= Skin /Renal
275
Detection of Anti-Nuclear Antibodies?
Indirect Immunofluoresence
276
ANA patterns
Homogenous
Speckled
Centromere
Nucleolar
277
ANA reactivity clarification?
ELISA, RIA and Immunoblotting
278
Anti-bodies to double stranded DNA?
Highly Specific for SLE
279
Anti-Sm (30%)
Anti-Ro (30%)
Anti-La
30% specific (except La) each for SLE
| All are anti-ENA (extractable nuclear antigen).
280
ELISA meaning?
Enzyme Linked ImmunoSorbant Assay
281
Jo-1
30% of Polymyosistitis
282
RNP
100% Mixed Connective Tissue Disease
283
Scl-70
A poor prognostic indicator for Scleroderma.
284
Most common glomerular disease?
IgA nephropathy.
285
IgA immune complexes deposited in mesangium.
IgA nephropathy.
286
Anti-GBM antibody
Goodpastures
287
Anti-CCP
Rheumatoid Arthritis
288
DR4 and DR1
Rheumatoid Arthritis
289
Citrulline
Rheumatoid Arthritis
290
Principle Antibodies in Rheumatoid Arthritis
```
Anti CCP (Specific 97%, sensitive 88%)
RF (Specific 65%, Sensitive 50-90%)
```
291
Anti-PR3+
Granulomatosis with Polyangitis (GPA)
292
Treatment for Granulomatosis with Polyangitis?
Cyclophosphamide
293
Anti-ACHr (receptor)
Myasthenia Gravis
294
Anti-MUSK (muscle specific tyrosine kinase)
Found in some anti-AchR negative MG
295
IgA EMA
```
Coeliac (90-100% sensitive and specific)
Dermatitis herpetiformis (50-70% sensitive, 90-100 specific)
```
False negative – gluten free diet
296
Commonest malignant disorder of plasma cells
Multiple Myeloma
297
Age of onset in Multiple Myeloma?
After age 50 yrs
298
>20% Abnormal looking BM plasma cells
Multiple Myeloma
299
Paraprotein in blood and/or urine
Multiple Myeloma
300
Bone destruction with osteoporosis or lytic lesions
Often seen in Multiple Myeloma
301
Test for paraproteins?
Electrophoresis
302
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
303
X-Chromosome (males) defect in B-Cell Maturation. Presents in early childhood.
XLA/Brutons Tyrosine Kinase Defect/X-linked agammaglobulinaemia
304
btk
Brutons Tyrosine Kinase
Vital in maturation of Pro-BCell to Pre-Bcell
Defect = agammaglobulinaemia = IgA, IgG and IgM def
305
Recurrent infections – RTIs (lungs & ears chronic OM)
| Meningitis and septic arthritis
Agammaglobinaemia.
306
Complications and Tx of X-linked Agammaglobinaemia?
IVIg and antibiotics
Complications...
Bronchiectasis
Chronic Sinus Damage
307
Antibody deficiencies
```
XLA
CVID
Hyper-IgM
IgA
Specific antibody deficiency
Transient hypogammaglobulinaemia
```
308
Infections soon after birth
- Recurrent bacterial
- Persistent Viral
- Opportunistic
- Persistent Thrush
Severe Combined Immunodeficiency (SCID)
309
Absence of T cells (
Severe Combined Immunodeficiency (SCID)
310
Treatment of SCID?
Isolation in +pressure
Antibiotics
Bone Marrow Transplant, possibly gene therapy.
311
X-linked (young men) Typically presents as a skin infection with +ve organisms (staph aureus, fungi, tc) with deep abscess formation
Chronic Granulomatous Disease
312
NADPH oxidase (Phox)
Chronic Granulomatous Disease
313
Treatment for chronic granulomatous disease?
Prophylaxis (co-trimoxasole, itraconasole)
| BMT
314
CD11a, 11b, 11c and CD18
Adhesion molecules (Neutrophil Function Disorder)
315
Failure in inactivation of complement and kinin systems
Angioedema (deep tissue swelling)
Any part of body
Airway & gut (recurrent abdominal pain)
No urticaria or itch (tingling described)
Late childhood or teenage years
Hereditary Angioedema.
316
Treatment for hereditary angioedema
Treatment
C1-Inh replacement (acute attacks)
Modified androgens (danazol or stanazol)
Bradykinin receptor anatagonists
317
Atophy
```
Type 1 IgE mediated allergy (most common allergy)
10% population.
- Asthma
- Hay Fever
- Eczema
- Foods
- Urticaria and angioedema
- Anaphylaxis
```
318
Type 2 Allergy
Autoantibody
319
Type 4
Patch Test (Angry Back Syndrome)
320
Important consideration in IgE allergies
Sensitisation does not mean necessarily mean clinical allergy!
Negative result does not exclude allergy
Patient may need a challenge test
Negative SPT does not exclude allergy
321
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
322
Gold Standard in Allergen Dx
Allergen Challange
323
Tx for Allergens
Avoid allergen – if possible
```
Anti-histamines
Self injectable adrenaline
Steroids – onset of action 6hrs
Individualised plan
life threatening reaction?
Chance of re-exposure?
```
Desensitisation – venoms, pollens
324
Indications for Glucocorticoids
Significant Acute Inflammation
325
Cortisol
Main Natural Glucocorticoid
326
Aldosterone
Main Natural Glucocorticoid
327
Prednisone and Cortisone
Biologically inactive synthetic
11 keto group requires activation to the 11-hydroxy group before having effect on cytosolic receptor.
Activated forms = Prednislone, Cortisol.
328
Long Acting Glucocorticoid?
Dexmethasone
329
Short Activng Glucocorticoid?
Prednisolone
Hydrocortisone
Methylprednisolone
Tramcinolone.
330
Steroid Dosing
High (20-40mg p/day)
Medium
Low (250mg given every 24-48 hrs
331
MEDICATION TO AVOID IN STEROIDS?
NSAIDS
332
Graft Rejection Pathophysiology
APC-TCR = CD4 proliferation, release of IL2 and recruitment of Cytotoxic CD8+Tcells
333
Agents used in Transplant Immunosuppression
Glucocorticoids
Calcineurin Inhibitors (Cyclosporine, Tacrolimus)
Antiproliferative/antimetabolic agents
Monclonal Antibody Therapies (cell specific)
334
Calcineurin Inhibitors
Cyclosporine, Tacrolimus (100x more potent).
Intracell signalling pathways to block IL2.
Mainstay of organ transplant.
S/E's Nephrotoxicity, Neurotixcity.
335
Sirolimus
TOR (Target of Rapamycin) inhibition.
| Thereby blocking IL2
336
Cell Cycle Inhibitors
Mycophenolate Mofetil
Inhibits Inosine, needed for nucleotide synthesis
Used in SLE
Azathioprine
Metabolised to 6MP in the liver.
337
Anti-IL2-Receptor Antibodies.
Daclizumab and Basiliximab
| Prophylaxis against organ rejection.
