1
Q
What affect does UVB have on the immune system?
A
- Reduces Langerhans cell numbers and APC ability
- Reduces KC’s expression of IL-1 and IL-6
2
Q
What breeds commonly get nasal arteritis?
A
St. Bernards, Giant Schnauzers, Newfoundlands, Basset Hounds, Scottish Terriers
3
Q
What is the effect of the following on Langerhans cells? Atopy, glucocorticoids, FIV+, contact dermatitis?
A
- AD: increased number of LC in atopic lesions
- GCs: impairs LC antigen presentation
- FIV+: loss of LC binding to T-cells (CD-4+ can’t bind MHCII)
- Contact dermatitis: LCs capture haptens to present and sensitize T-cells to
4
Q
Where are Merkel cells found in the skin? What is their function? What is their origin?
A
- Basal layer and bulge (of human hair follicle)
- Sensory perception (receive stimuli as KCs are deformed and respond by secreting chemical neurotransmitters; slow-adapting mechanoreceptor)
- Suspect neuro-endocrine origin
5
Q
What is the most reliable marker for Merkel cells?
A
KRT20
(also 8, 10, 18)
6
Q
What is a PRR? What are 4 different types and give some examples.
A
- A protein on an immune cell that recognizes and binds to DAMPs or PAMPs. This is part of the innate immune system.
TYPES: - Soluble: collectins, complement
- Within vesicles: TLRs 3, 7, 8, 9
- Cytoplasmic: Rig-1, NOD-like
- Membrane bound: TLR 1, 2, 4, 5, 6, lectins, langerin, dectins, integrins
7
Q
How do TLRs trigger the innate and adaptive immune system?
A
Innate: All TLRs (except for 3) use an adaptor protein (MyD88) to activate transcription factors NF-kB (IL-1, IL6, TNF-a) AND IRF3 (type 1 interferons - virus inhibition).
Adaptive: DAMPs bind TLR4 which induce macrophages and dendritic cells to produce cytokines which stimulate lymphocytes.
8
Q
What triggers: TLR2, TLR3, TLR4, TLR5, TLR7?
A
TLR2: lipoproteins from bacteria, viruses, parasites
TLR3: dsRNA from viruses
TLR4: LPS from bacteria and viruses
TLR5: flagellin from bacteria
TLR7: ssRNA, guanosine from viruses and bacteria
9
Q
What do RIG-like receptors (RLR) do?
A
Intracellular sensor that detects dsRNA from viruses to activate synthesis of type 1 interferons and NF-kB (pro-inflammatory cytokines.
10
Q
What do NOD-like receptors (NRL) do?
A
An intracellular sensor that when Bound by PAMPs activates the NF-kB pathway.
11
Q
RLRs and NRLs can trigger caspase 1. What does this do?
A
Caspase 1 processes and releases pro-inflammatory cytokines such as IL-1b and IL-18.
12
Q
What is a C-type lectin receptor (CLR)?
A
A large family of proteins that bind carbohydrates in a calcium-dependent manner. Some are membrane bound and some are soluble.
Membrane bound:
Dectins (Malassezia), mannose receptor (bacteria, candida, leishmania), selectins, DC-SIGN, Langerin
Soluble:
Mannose-binding lectin (candida, crypto, bacteria, leishmania, viruses) - important in complement activation!
13
Q
What are cadherins vs. integrins vs. selectins?
A
Cadherins are calcium DEPENDENT cell adhesion molecules (CAM) that mediate cell-to-cell adhesion. Examples: desmogleins, desmocolin, E-cadherin.
Selectins are calcium DEPENDENT cell adhesion molecule (CAM) involved in initial stages of “adhesion cascade”. Examples: E-selectin, L-selectin, P-selectin.
Integrins are calcium INDEPENDENT cell adhesion molecules (CAM) that mediate attachment of cells to other cells and ECM. Examples: Integrin a6b4, LFA-1, VLA-1, Mac-1
14
Q
What are types of adhesion molecules?
A
Cell adhesion molecules (CAM): selectins, cadherins, integrins
Junctional adhesion molecules (JAMs): LFA and Mac binding
Intercellular adhesion molecules (ICAMs): ICAM, VCAM
Soluble cell adhesion molecules (sCAMs): Se-selectin, sP-selectin
Immunoglobulin-like adhesion molecules (MAdCAM)
15
Q
What are JAMs?
A
Junctional adhesion molecules are cell surface proteins that are primarily located at tight junctions between epithelial and endothelial cells. They function as barrier regulation and immune cell migration.
Examples: JAM-2, JAM-3, PECAM-1 (opens up adhesion junctions for cell migration)
16
Q
What is ICAM-1?
A
Stabilizes cell-cell adhesion between endothelial and lymphocytes facilitating leukocyte transmembrane migration.
17
Q
What is VCAM-1?
A
Endothelial associated AFTER cytokine stimulation (IL-1, TNF-a, IL-4) stabilizing cell-cell adhesion and facilitating leukocyte transmembrane migration. Plays a role in melanoma metastasis.
18
Q
What is MadCAM-1?
A
Similar to ICAM and VCAM but on mucosal surfaces. Plays a role in IBD.
19
Q
What are P-type vs. S-type vs. C-type vs. L-type lectins?
A
Proteins that bind to carbohydrates.
- C-type are calcium dependent and involved in immunity and adhesion
- S-type (galectins) and function in the cytoplasm and ECM
- P-type frequently act as transport shuttles enzymes (mannose-6-phosphate receptors)
- L-type: acute phase proteins, binding of LPS to trigger classical complement
20
Q
What is mannose-binding lectin (MBL)?
A
Present at high levels in the blood that bind oligosaccharides (mannose, glucose, galactose) on yeast, bacteria, parasites and viruses.
When this binds, it triggers enzymes to cleave C4 and C2 followed by cleaving of C3 and initiating the complement cascade to target the pathogen for destruction.
21
Q
What are general functions of soluble PRRs?
A
- First line recognition of DAMPs
- Opsonization
- Complement activation (C1q for classical, MBL or filocolins for lectin)
- Neutralization (block microbial entry)
- Bridge to cellular immunity and adaptive immunity
Examples: complement, collectins, ficolins, pentraxins, LBP
22
Q
Describe the alternative, lectin, and classical complement pathways.
A
C3 is in the blood, tissues, neutrophils at all times present until it is triggered by one of the pathways.
- Classical: C1q encounters an antibody bound by invading microorganism (can’t be activated until antibodies are formed)
- Alternative: triggered when microbe cell wall meets a complement protein in the blood
- Lectin: triggered when a soluble PRR (ex. MBL, ficolin) binds microbial carbohydrates
23
Q
What are the steps in complement?
A
Initiation:
- Classical
- Alternative
- Lectin pathways
Amplification:
- Via C3 convertase enzyme
Terminal pathway:
- MAC aka TCC
- C2a: increased vascular permeability
- C3a: anaphylatoxin (microbial killing)
- C3b: opsonization
- C5a: anaphylatoxin, neutrophil chemotaxis and activation, increased vascular permeability, T cell development
- C5b: leukocyte chemotaxis & MAC
24
Q
What is an inflammasome? How does this cause disease in humans?
A
Triggered by PAMP/DAMP binding NOD-like receptors. An inflammasome is a large, intracellular, multi-protein complex which activates caspase 1 and caspase 11 leading to pro-inflammatory cytokines (IL-1, IL-18) and triggered cell death (pyroptosis).
In humans, inherited defects in the inflammasome are linked to uncontrolled inflammation.
25
What are components of the skin that function as a barrier? Start outwards and work inwards.
- Microbiome
- Keratinocytes: act as APCs, protective lipids, PRRs able to recognize PAMPs/DAMPs that release cytokines, chemokines, growth factors, AMPs
- Langerhans cells
- Resident T cells in the basal layer with LCs (balance of CD4/CD8, memory T cells, Treg)
- B cells
- Mast cells, apocrine glands, sebaceous glands (AMPs and lipids)
- Dermal dendritic cells
26
What are the steps involved in diapedesis? Discuss selectins, ICAM-1/VCAM-1, PECAM-1, JAMs.
1. Rolling
- P-selectin: platelets (a-granules) and endothelial cells (Weibel-Palade bodies), and incited by thrombin and histamine
- E-selectin: endothelial cells synthesize cytokines (TNF-a), mediating of rolling of neutrophils and monocytes
- L-selectin: on leukocytes (neutrophils, monocytes), mediates rolling on activated endothelium
2. Firm adhesion: only happens after damaged endothelium releases chemokines which bind leukocyte and increase their affinity for integrins.
- ICAM-1: on endothelium binds leukocyte integrin (LFA-1; neutrophils and monocytes, more acute)
- VCAM-1: on endothelium binds lymphocyte integrin (VLA-4; monocytes, eosinophils, more chronic)
3. Transmigration: most mobile is neutrophil which will arrive first via Leukotriene B4
- PECAM-1: guides leukocytes through intercellular junctions
- JAMS: support migration
- Integrins and enzymes degrade basement membrane to allow for cells to enter tissues
27
A dendritic cell (DC) is activated when a PAMP or DAMP binds its TLR. Differentiation of cDCs depends upon the antigen, dose, and location.
Binding of TLR9 (viral nucleic acids) is more likely to result in which dDC population?
Binding of TLR2 (proteoglycans), histamine, or substance P is more likely to result in which cDC population?
- TLR9: IL-12 -> DC1 (presents antigens to CD8+ T cells)
- TLR2: IL-25, IL-33, TLSLP -> DC2 (presents antigens to CD4+ T cells) -> Th2 and Th17 responses
28
What prevents a T-cell from recognizing and responding to antigens in it's environment?
T-cell receptors can only recognize antigen peptides attached to MHC molecules.
29
What signals are required for T-cell differentiation?
- TCR binding antigen on MHC
- Tightly bound for a long time
- Co-stimulatory factors
30
Which cDCs would release which cytokines, and what T-cell differentiation would it lead to?
- IL-12
- IL-4
- IL-23
- cDC1: IL-12 -> Th1
- cDC2: IL-4 -> Th2
- cDC2: IL-23 -> Th17
31
What must be activated first before T-cells can differentiate?
Naiive CD4+ T cell activation must be done first (they direct everyone else on what to do).
32
When an APC presents an antigen to a T-cell via MHC-TCR interaction, what three pathways can be incited?
- NF-kB -> TNF-a, IL-2, IL-6 -> Th1
- NFAT -> TNF-a, IL-2, INF-y
- MAPK -> T-cell proliferation
33
Helper T cells activate B cells to do what?
B-cell division, somatic mutation (introduce random mutations), affinity maturation (selective process to find the mutations that lead to an increased strength of antibody binding) leading to either plasma cell or memory B cells
B-cells also function as APCs
34
CD8+ T-cells can kill cells by what mechanisms?
1. Perforin granzyme: lethal hit of granules containing perforins, granzymes, granulysin, TNF-b, caspase 9 (especially viruses)
2. Fas-Fas Ligand: Fas binds, death signaling complex, caspase 8 and caspase 10 start, caspase 3 finishes leading to apoptosis
35
What cytokine can activate macrophages? What do activated macrophages then do?
- INF-y
- Increased phagocytosis, secrete proteases, interferons, vasoactive molecules, complement components, respiratory burst, NO
36
What is the advantage of memory cells?
They can respond more rapidly when they re-encounter antigens in the future
37
What is central vs. peripheral tolerance?
Central: immature self-reactive lymphocytes die or alter their specificity
Peripheral: mature lymphocytes that recognize self-antigens escape into circulation or secondary lymphoid organs and either die or alter their specificity under the regulation by Treg
38
What is positive vs; negative T-cell selection? What happens to a T-cell that has high, intermediate, or low affinity?
Positive: only T-cells that recognize MHC's survive
Negative: T-cells that bind too tightly are deleted or edited
- High affinity: deleted or edited
- Intermediate affinity: Treg cells
- Low affinity: conventional T-cells
39
What is anergy? How is this implicated in chronic infections and cancer?
Native T-cells exposed to an antigen without co-stimulation resulting in hypo-responsive T-cells.
The binding of the TCR without co-stimulatory molecules leads to inhibition of NF-kB pathway which can last for weeks. This prevents attack of healthy tissues but may lead to the immune system not responding adequately leading to cancer or chronic infections.
A balance is needed!
40
What is adaptive tolerance vs. quiescence vs. ignorance vs. T-cell exhaustion?
- Adaptive: prolonged antigen stimulation leads to maintained anergy (inhibiting cell proliferation and cytokine production)
- Quiescence: T-cells are inactive
- Ignorance: T-cells aren't able to recognize an antigen because it hasn't been properly presented or is lacking the proper receptor
- T-cell exhaustion: T-cells have experienced prolonged TCR with co-stimulation (chronic antigen stimulation) leading to poor function
41
How do doses of antigens affect tolerance? How does this relate to allergy immunotherapy?
Low doses - induce tolerance
Moderate doses - antibody production
High doses - Immune paralysis (tolerance)
AIT uses low doses of antigens to try to shift the immune system towards tolerance.
42
What are mechanisms of peripheral tolerance?
- Anergy
- T-reg: suppress auto-reactive cells
- Deletion: T-cells begin to express Fas with each antigenic stimulation, making them more sensitive to apoptosis with repeated or prolonged antigenic stimulation (deleting possible self-reactive T-cells)
- Immune privilege: some tissues actively suppress inflammation at all times
43
How could a deletion of Foxp3 lead to allergies?
Deletion or mutation leads to the absence of hypo-functioning T-regs. This can lead to systemic immune disease or infection (diabetes, allergies, IBD).
44
What happens if B cells are repeatedly exposed to antigenic stimulation and they all transform into plasma cells?
This leaves no memory B-cells left to respond to antigens which results in tolerance (peripheral B cell tolerance).
45
How long does tolerance last for?
As long as the antigen is present.
46
What are two ways in which immune-mediated disease is induced? Which one is more common?
1. Normal immune response to abnormal antigen
- Previously hidden auto-antigens are exposed to non-tolerant T-cells
- Antibody binds antigen, it can contort the shape of the antibody and expose new epitopes on the Fc region
2. Abnormal immune response to normal antigen (more common)
- Needs to be a sustained failure of tolerance
- CD95 destroys self-reactive lymphocytes in the thymus. If CD95 has a defect it permits abnormal T-cells to survive
- Normal immune response to a foreign antigen can subsequently spread to self-antigens
47
What risk factors may increase susceptibility to auto-immune disease?
1. Genetics: key determinants for disease susceptibility
- Defects in MHC. Breeding has lost MHC polymorphisms: Boxers (DRB1*04 gene) respond to an unusually narrow range of antigens, reducing their resistance to infectious agents and making them more susceptible to immune disease.
2. Spaying and neutering increases risks of diseases
- hypothyroidism, Addison's, IMHA, IMTP
3. Intestinal microbiota:
- Breakdown in mucosal GI barriers results in excessive leakage of bacteria.
- Dysbiosis may affect development of autoimmune disease
48
Describe a type 2 hypersensitivity reaction using pemphigus foliaceous as an example.
1. Loss of immune tolerance (triggered by genetic predisposition, drugs, UV light, chronic infection?) resulting in autoantibodies against desmosomal proteins
2. B-cells produce IgG(4) autoantibodies against desmosomal cadherins. IgG binds desmocolin-1 (dogs). Once ab - ag binds, this changes the shape of the IgG exposing Fc domains which complement proteins can recognize.
3. C1 complex binds the exposed Fc portion of the ab-ag IgG leading to the complement cascade -> C3a and C5a -> recruiting neutrophils and macrophages, degranulating mast cells and formation of subcorneal pustule. Protease activation (plasmin, KLK) may amplify the lesion.
49
What cytokines, chemokines are up-regulated in lesional PF skin? What cells are involved?
- IL-6, IL-8, IL-18, TNF-a
- GM-CSF, MCP-1
- NK cells, Th1, Th2, Th17, Th22, neutrophils and dendritic cells
50
When can you start a taper of glucocorticoids during the induction phase when treating for pemphigus foliaceous? How do you taper?
- When no new lesions are forming for a minimum of 2 weeks AND 80% of the original lesion have healed.
- Taper by 25% every 2-4 weeks until finding lowest effective dose.
51
What dog breeds and what cat breeds may be predisposed to PF?
- Akita, Chow Chow, Bearded Collies, Newfoundlands, Dobermans, Spitz, and Dachshunds
- DSH, Siamese, Ragdoll?
52
Compare and contrast pemphigus foliaceous, pemphigus vulgaris, and paraneoplastic pemphigus.
- All IgG auto-immune skin disease
- PF and PV often are idiopathic, PNP has underlying neoplasia (thymoma, thymic lymphoma, splenic sarcoma)
- PF is the most common auto-immune skin disease, PV is rare, PNP extremely rare
- Different targets: Dsc-1 (dogs) in PF vs. Dsg-3 in PV, resulting in skin disease (PF) and mucosal, MCJ, skin involvement vs. multiple different targets in PV.
- Subcorneal (PF) vs. suprabasal (PV) vs. PNP has histo consistent with PV but also EM
- AKs (PF) vs. tombstoning (PV)
- Often systemic illness (PF) vs. frequent pain of the oral cavity (PV 93% have oral lesions)
- PV may have a more guarded prognosis than PF. PNP has poor prognosis.
53
Where is dsg 1 vs. dsg 3 expressed?
Dsg 1 - upper layers of the epidermis
Dsg 3 - basal layer, higher concentrations in the mucosa
54
What are 3 mechanisms of acantholysis in pemphigus vulgaris?
1. Steric hindrance: reduces mechanical adhesion between keratinocytes due to reducing trans-adhesive interactions between cells via dsg3
2. Signal-transduction: PV autoantibodies transduce intracellular signals that initiate pathways (MAPK, caspase 3) which disassemble desmosomes.
3. Desmoglein depletion: PV IgG induces endocytosis of Dsg3 into endosomes, once desmosome is depleted of Dsg3 it can weaken cell adhesion
55
A biopsy reveals suprabasal acantholysis, tombstoning, and a significant hyperplastic epidermis. What is your top differential?
Pemphigus vegetans
56
What is Neumann-type vs. Hallopeau-type, and which is a better prognosis?
- Neumann-type: large erosions -> more severe plaques
- Hallopeau-type: small pustules -> milder plaques (thought to have better prognosis)
57
Paraneoplastic pemphigus has polyclonal targets, but which two are targeted most consistently?
Envoplakin and periplakin
58
What is the neoplasia that most frequently causes paraneoplastic pemphigus in people?
Non-hodgkin's lymphoma
59
Answer the following regarding bullous diseases:
1. Which affects the mucosa more than others?
2. Which affects haired skin more than others?
3. Which 3 are most common?
4. Which has round lesions with scarring?
5. Which is more common in young, male, Great Danes?
6. Which is rich in eosinophils vs. neutrophilic rowing?
7. Which is vancomycin a trigger in people?
8. Which has been seen in pigs and macaques?
9. Which has colchicine been recommended due to anti-neutrophilic properties?
10. Which do most feel sick?
11. What is seen on histo?
1. MMP
2. BP
3. MMP, BP, EBA
4. MMP
5. EBA
6. BP vs. EBA
7. LIgA
8. BP
9. EBA
10. EBA
11. subepidermal vesicles with scant inflammation.
60
What are the targets for MMP?
a. BPAG1e
b. Collagen XVII
c. Laminin 332
d. Collagen 7
MMP = 3 targets (all except the deepest)
a. BPAG1e
b. Collagen 17 = MAIN
c. Laminin 332
Most have complete remission with frequent flares
61
What are the targets for BP?
a. BPAG1e
b. Collagen XVII
c. Laminin 332
d. Collagen 7
BP = 2 targets
a. BPAG1e
b. Collagen XVII = MAIN
Most have been able to discontinue medications after disease is in remission.
62
What are the targets for Mixed AISBD?
a. BPAG1e
b. Collagen XVII
c. Laminin 332
d. Collagen 7
Mixed AISBD = 2 targets (this one is bad, so the two deepest targets)
c. Laminin 332
d. Collagen 7
63
What are the targets for EBA?
a. BPAG1e
b. Collagen XVII
c. Laminin 332
d. Collagen 7
EBA = 1 target, BAD!
d. Collagen 7
Most can be managed with immunosuppressants
64
What are the targets for bSLE?
a. BPAG1e
b. Collagen XVII
c. Laminin 332
d. Collagen 7
bSLE = 1 target, BAD!
d. Collagen 7
One case was euthanized
65
What are the targets for JEBA?
a. BPAG1e
b. Collagen XVII
c. Laminin 332
d. Collagen 7
JEBA = 1 target (junctional)
c. Laminin 332
Standard therapies, often can be stopped without relapses
66
What are the targets for Linear IgA dermatosis?
a. BPAG1e
b. Collagen XVII
c. Laminin 332
d. Collagen 7
Linear IgA dermatosis = 1 target
b. Collagen XVII, in particular LAD-1 antigen
67
What are the targets for Pemphigus gestationis?
a. BPAG1e
b. Collagen XVII
c. Laminin 332
d. Collagen 7
PG = 1 target
b. Collagen XVII
Resolved after OVH
68
Which three AISBDs show up on the dermal side of the salt split?
Where would these same three show up on PAS staining?
- EBA, mixed, bSLE
- Epidermal (mixed not listed)
69
Which three AISBDs CONSISTENTLY show up on the epidermal side of the salt split?
Where would these same three show up on PAS staining?
- BP, PG, LAD
- Dermal
70
Which two AISBDs could show up on either or both sides of the salt split?
JEBA, MMP
71
Describe a type 3 hypersensitivity using lupoid diseases as an example.
- UVB causes apoptosis of skin cells, release of nuclear antigens
- Clearance of apoptotic debris is inefficient (defective macrophages, leaving exposure to DNA) leading to creation of auto-antigens
- Antibody-Antigen (DNA) complexes (IgG, IgM possibly C3) bind on TLR (4, 7, 9??) of dendritic cells leading to secretion of type 1 interferons
- Basal cells become targets for cytotoxic T cells leading to interface dermatitis (apoptotic keratinocytes at basal cell, thickened BMZ, pigmentary incontinence)
=> deposition of immune complexes in the basement membrane, neutrophil and macrophage infiltration, release of proteases and basal cell apoptosis
72
Compare and contrast VCLE vs. ECLE vs. MCLE vs. DLE including targets, predisposed, clinical picture, and histopathology?
1. Targets:
- VCLE -> Ro/SSA or La/SSB antigens
- Others unknown or BMZ components
2. Predisposed:
- VCLE: shelties, collies, UV!
- ECLE: Young GSP, Vizsla
- MCLE: GSD, females
- DLE: GSD, collies. UV!
3. Clinical:
- VCLE: ulcers skin + MCJ + pinna +/- oral
- ECLE: scale, scarring, possible pruritus
- MCLE: painful ulcers at MCJ (anus, genital, lips). Lesions don't heal with scarring
- DLE: ulcer at nasal planum, lesions heal w/scarring
4. Histo: all have interface
- VCLE: interface + epidermal vesiculation
- ECLE: interface + loss of sebaceous glands
73
Which lupoid diseases may be related to UV exposure?
VCLE, DLE
74
What chromosome SNP is implicated in ECLE? Mode of inheritance?
SNP on CFA 18 chromosome
autosomal recessive
75
Which lupoid disease is associated with arthralgia?
ECLE
76
Which lupoid disease is associated with azoospermia?
ECLE
77
Which breeds have been reported to have generalized DLE?
Chinese Crested and others
78
What has been reported as a possible progression of DLE?
SCC
79
What anti-malaria therapy has been used to treat DLE in humans?
Hydroxychloroquine
80
A Greyhound presents with purpura and necrosis of the skin affecting the groin. The lesions are well-demarcated, deep, and slow to heal. What laboratory test should you run? What could be the cause of this?
Cutaneous and renal glomerular vasculopathy. Some develop acute renal failure. Thought to be from verotoxin from E. coli in contaminated beef products.
81
What are type 1, 2, and 3 of cryoglobulinemia?
T1: monoclonal (lymphoproliferative disorder)
T2: monoclonal + polyclonal (autoimmune)
T3: polyclonal (infections)
82
Which breeds are are sterile nodular panniculitis seen in more commonly?
Dachshunds, miniature poodles, collies
83
A biopsy with special stains, tissue cultures, and urine blastomycosis antigen test have been performed confirming sterile nodular panniculitis. What's your next step?
Blood work, abdominal ultrasound, etc. Often underlying diseases can cause this. Possibly pancreatic disease (pancreatitis, neoplasia) or other internal medicine disease.
84
Which dog breed is seen frequently in SLO?
Gordon Setter
85
Describe a type 4 hypersensitivity reaction using erythema multiforme as an example.
Sensitization phase
- A trigger (infection, drug, vaccine, neoplasia) occurs. Keratinocytes express foreign or altered self-antigens from drug metabolites, viral peptides, neoplastic agents of damaged self-proteins.
- Langerhans cells travel to the lymph node and present the self-antigen to CD4+ and CD8+ T-cells. T-cells activate, proliferate, and differentiate into memory T-cells.
Elicitation phase:
- CD4+ Th1 cells recognize the self-antigens on keratinocytes and secrete INF-y which amplifies the response.
- CD8+ T-cells recognize antigen-bearing keratinocytes and induce apoptosis (perforin-granzyme, Fas-Fas, TNF-a mediated) -> interface dermatitis with satellite cell necrosis.
86
What is erythema multiforme usually associated with in people? In pets?
Humans: herpesvirus.
Pets: idiopathic > drugs (TMS, penicillin, cephalosporins), infections, neoplasia.
87
What is the theory of the immune reaction in erythema multiforme?
Viral particles in the keratinocytes attract Th2 cells increasing INF-y leading to cytotoxicity and apoptosis of keratinocytes.
88
How can EM, SJS, and TEN be differentiated clinically?
EM has target-like papules, plaques, erosions (less than 10% body surface affected). Usually idiopathic.
SJS has vesicles, erosions, mucosal ulceration (less than 10% body surface affected). Painful. Usually drug involvement.
TEN has extensive necrosis (over 30% body surface effected). Severely painful and life-threatening. Usually drug involvement (TMS, cephalosporins, penicillins, flea dip).
89
Compare and contrast alopecia areata vs. psesudopelade.
- AA more common in dogs, PP more common in cats??
- Cause: AA - stress may contribute, PP - genetics may contribute
- Histopathology: AA - lymphocytic bulbitis, PP - lymphocytic inflammation mid-isthmus (near the bulge where there are stem cells)
- Clinical: AA - often affects face, PP - often affects face then spreads from there
- Diagnosis: AA may show a ! on trichography
- Therapy: AA - GC, CsA, PP - no therapies known to work but may try GC, CsA, chlorambucil
- Prognosis: AA - hair may regrow a different color, PP - permanent scarring alopecia
90
A golden retriever puppy has swelling of the face, lymph nodes, lethargy, SQ nodules, lameness. He is put on a high dose of steroids and the clinical signs resolve. What is the prognosis?
Juvenille cellulitis, heritability suspected. Often in young but it can be in older dogs. Relapses are uncommon.
91
What is the suspected etiology of granuloma pyogranuloma syndrome?
It may be related to an immune resonse against persistent endogenous or exogenous antigens, such as Leishmania sp., and/or mycobacterium, causing a granulomatous inflammatory reaction.
92
Compare and contrast Well's syndrome vs. Sweet's syndrome.
- W: eosinophils vs. S: neutrophils
- W: urticarial-like vs. S: painful nodules
- W: mild lethargy vs. S: fever, lethargy, anorexia
- W: GI disease / metronidazole or hypersensitivity vs. S: arthritis / carprofen or systemic infection / neoplasia
- W: pruritus mild or absent vs. S: pruritus absent
- W + S: withdraw inciting medication + GCs
93
Compare and contrast VKH-like syndrome and vitiligo.
- Both type 4 hypersensitivity
- VKH: CD4+ Th17 and CD8+ vs. V: CD8+
- VKH: Auto-immune T-cells attack melanocytes in multiple organs (eye, skin, meninges, inner ear) VS. V: autoimmune destruction of epidermal melanocytes
- VKH: Akitas, Samoyeds, Husky, rare in cats vs. V: Doberman, Boxer, Belgian Tervuren, cats, horses (Appaloosa), cattle
- VKH: Depigmentation, inflammation, uveitis vs. V: slowly progressive depigmentation
- VKH: rapid vs. V: slow
- VKH: prednisone vs. V: none needed
- VKH: genetic basis in Akitas (DQA100201) vs. V: acquired, multi-factorial but hereditary component possible
- VKH: uveitis starts first, then progresses to the skin, often the face
94
What stain will highlight amyloidosis?
Congo red
95
What virus is plasma cell pododermatitis been reported to be associated with in 63% of the cases? What other laboratory abnormality might be noted?
FIV+
Hyperglobulinemia
96
What complications could result from a cat with plasma cell pododermatitis?
Immune mediated glomerulonephritis and/or amyloidosis could be fatal
97
What is considered a histiocyte?
Dendritic cells (interstitial including dermal)
Langerhans cells
Macrophages
98
Which histiocytes have CD1a+?
All histiocytes
99
What cytokine do Langerhans cells need from keratinocytes for differentiation? What do they differentiate from?
- TGF-b1
- Dermal CD14+ precursor cells
100
Which cell is identified by the following: E-cadherin, Thy-1/CD90, CD11d?
E-cadherin: epidermal langerhans cells
Thy-1/CD90: Dermal interstitial dendritic cells
CD11d: Blood monocytes
101
What histiocytes are CD11c+?
Dendritic cells: interstitial DC and Langerhans cells
102
What is CD34+ the precursor to?
Macrophages
103
Which cells are positive to the following? CD80/86, CD4, CD3, CD18?
CD80/86: APCs including histiocytes
CD4: reactive histiocytes!!
CD3: T-cells
CD18: macrophage, monocyte, granulocyte
104
Defective interaction of what may contribute to reactive histiocytoses?
Interaction of dendritic cells and T-cells
105
Biopsy reveals a 'top heavy' lesion. What IHC can you use to differentiate two top differentials?
CD3 (T cells) and CD18 (histiocytes) to differentiate CTCL from a histiocytoma.
106
You see a Shar Pei with hundreds of cutaneous nodules that come back consistent with histiocytomas. What's the prognosis?
50% of dogs with canine cutaneous langerhans cell histiocytosis were euthanized due to complications involved in management of extensively ulcerated lesions and delay in regression (some may persist for 10 months)
107
What cells are implicated in histiocytoma, histiocytic sarcoma, and reactive histiocytosis?
Histiocytoma: langerhans cell (E-cadherin+)
Histiocytic sarcoma: dendritic cell (CD11c+) or macrophage (CD11d+)
Reactive histiocytosis: dendritic cell (CD11c+, but also CD4+ because it's reactive)
108
What is the difference in histopathology pattern between histiocytoma and reactive histiocytosis?
Histiocytoma: 'top heavy' = LCs
Reactive histiocytosis: 'bottom heavy' = dendritic cells
109
Which disease is associated with mutations in tumor suppressor genes CDKN2A, RB1, and PTEN?
Bernese Mountain dogs with histiocytic sarcoma
110
Which disease often starts with a problem affecting a joint in flat coated retrievers?
Histiocytic sarcoma
111
How can you differentiate a histiocytic sarcoma from reactive histiocytosis?
Both will be CD11c+ but only reactive histiocytosis will have Thy1/CD90 and CD4.
If histiocytic sarcoma is hematopoetic origin (macrophage), it will be CD11d+.
Histiocytic sarcoma is aggressive & metastatic (spleen, lung, skin, brain, LN, BM, synovial fluids). They are sick and it is a poor prognosis.
112
Compare and contrast feline progressive histiocytosis (FPH) and feline pulmonary langerhans cell histiocytosis (FPL).
- FPH: dendritic cell vs. FPL: langerhans cell (E-cadherin+)
- FPH: a more indolent version of histiocytic sarcoma (dendritic cells) which is slowly progresses (may wax and wane but do not go away, some cats get expansive, metastatic disease) vs. FPL: in aged cats that can lead to respiratory failure. This is a reactive disorder which may resolve with cessation of exposure to smoke.
113
Which markers need fresh vs. formalin tissue for evaluation of histiocytic disease? CD1a, CD90, CD4, CD11c, CD18, MHCII, E-cadherin.
CD1a, CD4, CD11c: fresh tissue only
CD90, CD18, MHCII, E-cadherin: formalin okay
114
What is CD207a marker for?
Langerin
115
Which cell is capable of mediating regression of a histiocytoma?
CD8+ T-cells
116
Compare and contrast reactive cutaneous histiocytosis (CH) with systemic histiocytosis (SH).
- Histopathology and markers will be the same. Both will have 'bottom heavy' topography.
- SH may have variable clinical signs depending on the severity and extent of disease but may include anorexia, weight loss, stertorous respiration and marked chemosis.
- CH + SH may have skin nodules distributed over the entire body including the scrotum, nasal apex, nasal planum, eyelids.
- Both may have disease that waxes and wanes
LT ACVD
flashcards
Decks in class (16)
# Cards
-
Genodermatosis88
-
Large Animal96
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Nail terminology22
-
Structure / Function130
-
Cytokines48
-
Infectious disease220
-
Parasitology112
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Exotics144
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Immune function116
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Internal Medicine + Oncology224
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Nutrition, environmental, trauma113
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Pharmacology235
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Dermatohistopathology72
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Otology134
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Atopy166
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Psychoneurodermatology60
