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ECEIM > Immunology > Flashcards

Immunology Flashcards

1
Q

What are the 2 main components of the immune system?

A
  1. Innate Immunity
  2. Adaptive Immunity
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2
Q

What are the innate immune system and name several effector cells?

A

Available for immediate defence with no prior exposure required!
Components: Physical and chemical barriers, Circulating cells, complement, cytokines, interferons, defensins

Cells: Neutrophils, eosinophils, mast cells, macrophages, dendritic cells

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3
Q

What components of complement lead to more inflammation?

A

Anaphylatoxins = C3a and C5a

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4
Q

What is the final outcome of complement activation?

A

Stimulates activation of terminal complement components (C5b-C9-membrane attack complex)

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5
Q

What is a TLR?

A

Toll-like receptor - recognizes intracellular and extracellular bacteria/virus
On neutrophils - Result in cytokine production = Inflammatory response

TLR2 - Bacterial lipopeptide
TLR4 - LPS

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6
Q

What is an NLR?

A

NOD-like receptor - recognizes intracellular bacteria/virus
On neutrophils - Result in cytokine production = Inflammatory response

NLRs = Bacterial lipopeptides

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7
Q

What are cytokines and chemokines?

A

Cytokine: Proteins that are made by affector cells to affect behavior of other cells
Chemokines: Cytokines that are important for chemotaxis

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8
Q

Name the 3 cytokines important for inflammation/fever.

A

IL-1
IL-6
TNFa

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9
Q

What are 2 major chemokines?

A

IL-8
CXCL1

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10
Q

What are the 3 major cell types of adaptive immunity?

A

Lymphocytes (B and T cell)
Antigen-presenting cells

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11
Q

What is humoral immunity?

A

B cells recognize antigen through surface-bound Ig> Once activated to become a plasma cell or long-lived memory cell = Secrete Ig, which bind pathogens in extracellular space - leading to their destruction through phagocytosis and complement binding

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12
Q

What is cell-mediated immunity?

A

T cells (via T cell receptors) recognize INTRACELLULAR antigens on cell surface of antigen-presenting cells (DO NOT bind free antigen, unlikely B cells)! Based on specialized cellular glycoproteins (gene cluster) = Major Histocompatibility Complex (MHC). Once activated, T cell differentiate into cytotoxic cells (CD8+) or helper cells (CD4+)

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13
Q

Cytotoxic T cells are CD___+.

A

CD8+

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14
Q

Helper T cells are CD___+.

A

CD4+

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15
Q

Name 3 antigen-presenting cells.

A

Macrophages, dendritic cells, B cells

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16
Q

What is the role of an antigen-presenting cell?

A

Along with MHC internalize, process, and present antigen+MHC on their cell surface to be recognized by T cells

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17
Q

Where do B cells and T cells “live” in the body?

A

B cells = BM
T cells = Thymus

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18
Q

What is clonal selection?

A

Single lymphocyte progenitor produces millions of cells with DIFFERENT and SPECIFIC antigen receptor on each cell - occurs through rearrangement of gene segments in variable region of antigen receptors EACH LYMPHOCYTE EXPRESSES ONLY 1 SPECIFIC RECEPTOR

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19
Q

What happens once a lymphocyte is activated?

A

Interaction of the receptor with a foreign antigen with sufficient binding = activates lymphocyte → Produces CLONES with the SAME SPECIFIC receptor. Clones are known as effector cells, capable of eliminating antigens

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20
Q

How do T cells differ from B cells in terms of differentiation?

A

T cells are MHC restricted!! T cells can recognize foreign antigen only in form of peptide bound to a self MHC molecule on APC.

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21
Q

What is positive selection?

A

T cells must be able to recognize the body’s own MHC molecules (since they are MHC restricted and can only recognize a foreign antigen when it is bound to a self MHC molecule on an APC)

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22
Q

What is negative selection?

A

T cells must be able to recognize self-peptides bound to self MHC molecules and become self tolerant. Cells binding with high affinity are deleted = negative selection

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23
Q

What happens when a T cell fails positive and negative selection?

A

It undergoes apoptosis
Estimated that 98% of immature T cells die this way

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24
Q

Which lymphocyte is produced throughout life?

A

B cells

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25
Q

What are the major steps in lymphocyte migration to sites of inflammation?

A
  1. Teter and rolling: Based on P and E selectins on endothelial cells or L-selectin (LN). Rolling mediated by binding of integrins (WBCs) to VCAMS or ICAMS (on endothelial cells)
  2. Activation: Based on chemokines (IL-8)
  3. Arrest: Based on b integrins to ICAMs and MadCAMs
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26
Q

What portion of an antibody binds to the antigen?

A

Variable region (Fab) - varies extensively to match antigen variety

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27
Q

What portion of an antibody binds to the APC?

A

Constant region (Fc) - leads to recruitment of additional immune cells and destruction of the pathogen

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28
Q

What determines the antibody isotype and name the 5 types of antibodies?

A

Constant (Fc) region determines the isotype
IgM (pentamer), IgG, IgD, IgE, IgA (Dimer)

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29
Q

How is a B cell activated?

A

Antigen binding to transmembrane B Cell antigen receptor stimulates clonal expansion (lots of phosphorylations) and differentiation to an antibody-secreting plasma cell (short-lived) or memory cells (long-lived) occurs

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30
Q

What is a common leukocyte antigen?

A

CD45 (present on all WBCs) - Transmembrane surface glycoprotein

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31
Q

What is the main function of the MHC?

A

To process and present pathogenic peptides to 2 distinct classes of T cells

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32
Q

What is the difference btwn MCH I and MCH II molecules?

A

MHC I: a chain and b2 microglobulin - Does NOT cross the membrane = Expressed on majority of nucleated cells
MCH II: a and b chains - crosses the membrane = Mainly expressed in APCs and in thymus (self-recognition)

Great polymorphism is present in MCH molecules

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33
Q

What is the role of MCH Class I in antigen processing and presentation?

A

Presents peptides to CD8+ (cytotoxic, killer cells)
Pathogens that are found in cytosol (viruses, tumor antigen, some bacteria) = Cell death
Cytosolic pathgenic proteins are degraded by proteosomes and delivered to ER where MHC I molecule is ready , peptide binding occurs = MHC I: Peptide complex transported to surface where it is exposed to CD8+ T cells

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34
Q

What is the role of MCH Class II in antigen processing and presentation?

A

Present peptides to CD4+ (T helper 1 or 2). Th1 - Acitvate inflammatory cells to kill intravesicular pathogens, Th2 - activate B cells to secrete Ig to eliminate extracellular bacteria/toxin
Antigen exists or is transported to intracellular vesicle and degraded into peptides, which fuse with MCH II and move to cell surface and exposed to CD4+ cells.

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35
Q

What is the difference between Th1 and Th2?

A 
Th1 = Activate inflammatory cells to kill pathogen (intravesicular)
Th2 = Activate B cells to produce Ig (extracellular)
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36
Q

What are the components of the T cell receptor complex?

A

Resembles the Fab portion of Ig (contains constant and variable region in a and b chains
Associated with CD3 complex (intracellular signalling) and CD45 (on all WBCs)
Co-receptor: CD4 or CD8 (some carry both)

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37
Q

What is the superantigen?

A

Binds ACROSS the MCH:T cell receptor (without processing) = Activation leads to massive production of cytokines by CD4 cells that leads to SIRS!!!
Bacteria (Stap enterotoxins, and some viral proteins)

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38
Q

Discuss the activation of naïve T Cells to effector T cells.

A
  1. Naïve T cells migrate to peripheral lymph organs where they are exposed to APCs (MP, dendritic cells, B cells) - Encounter of T cells with an antigen (on APC surface) = Primary immune response
  2. Recognition of MCH: Antigen complex
  3. CO-STIMULATORY SIGNAL delivered by same APC - binding of cell surface molecule B7 found on APC to CD 28 on T cell
  4. Activated T cells make IL-2 = Drives T cell growth and clonal proliferation = Armed effector cell that is capable of carrying out cytotoxic or helper functions WITHOUT co-stimulation
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39
Q

What 2 steps are required for T cell activation?

A
  1. Recognition of MCH: Antigen complex
  2. CO-STIMULATORY signal delivered by SAME APC (Binding of cell surface molecule B7 found on APC to CD 28 found on T cell)
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40
Q

Which cytokines result in Th1 vs Th2 T cell development?

A

IL-12 drives inflammatory or Th1 response (Cell-mediated immunity)

IL-4 drives a helper or Th2 response (humoral immunity)

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41
Q

What cytokines are seen with Th1 cells?

A

IFN gamma, TNF alpha and beta, IL-2

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42
Q

What is IFN gamma and TNF alpha?

A

Cytokines that are macrophage activators

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43
Q

What is IFN gamma?

A

Cytokine that blocks viral replication

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44
Q

What is TNF ß?

A

Cytokine that is cytotoxic

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45
Q

What is IL-2?

A

Cytokine that is needed for growth of Th1 cells

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46
Q

What are Th2 cytokines?

A

IL-4, 5, 6, 10, TGF ß

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47
Q

What is IL-4?

A 
Cytokine that is a growth factor for Th2 cells and B cells
Induced class switch from IgG to IgE
48
Q

What is IL-5?

A

Cytokines that induced IgA switch and activates eosinophils

49
Q

What is IL-6?

A

Proinflammatory cytokine-induced acute phase response

50
Q

What is IL-3?

A

Cytokine that is hematopoietic growth factor that activates mast cells

51
Q

Name 4 primary mechanisms of the humoral immune response.

A
  1. Neutralization: Binding to extracellular pathogens to inhibit toxic effects
  2. Opsonization - facilitation of uptake and destruction of pathogens by Ig binding to pathogen at Fab region and binding to the Fc receptor of phagocytic cell
  3. Complement Activation - Leads to enhanced opsonization and cell lysis
  4. Functions as APC with MCH II
52
Q

Which cell type plays a role in isotype switching of B cells?

A

Th2 cells

53
Q

What is a plasma cell?

A

B cells that has differentiated. Lacks surface Ig for bindings and contains low to zero MHC II = Plasma cells are no longer able to interact with antigen OR T cells
Ig secretion INDEPENDENT of these factors
Life span = 4 wks

54
Q

What is immunologic memory?

A

Ability of immune system to respond more rapidly and effectively to a pathogen that is has encountered before. Due to pre-existence of clonally expanded population of antigen-specific lymphocytes (controversial how memory is maintained)
Gives ability to vaccinate or immunize

55
Q

What is the primary antibody response?

A

IgM and then it changes to IgG +/- other subtypes

56
Q

Name 5 Fc receptor bearing cells.

A

Macrophages, PMN, nautral killer cells, eosinophils, mast cells = All secrete toxic mediators when Fc receptor engaged

57
Q

What are the most effective opsonins?

A

Antibodies and complement

58
Q

What are the 3 pathways of complement?

A
  1. Alternative Pathway (innate)
  2. Lectin Pathway (innate)
  3. Classical Pathway (adaptive)
59
Q

How are the innate complement pathways activated?

A

Recognizing PAMPs

60
Q

How is the adaptive/classical pathway of complement activated?

A

Antibodies that are bound to foreign antigen

61
Q

Which part of complement results in opsonization of microbes?

A

C3b

62
Q

Which part of complement results in inflammation?

A

C5a (chemoattractant)

63
Q

What are the 3 main steps of complement activation?

A
  1. Complement must be activated (PAMP or antibody:antigen)
  2. C3b must be generated
  3. Terminal complement complex assembled through amplification pathway
64
Q

What is an example of a complement deficiency that is seen in horses?

A

Inherited forms of complement dysfunction or deficiency have not been reported in the horse. However, the foal is born with low serum complement activity, and colostrum is not a significant source of complement.

Therefore, foals are transiently deficient in serum opsonic capacity and rely on their own production of complement after birth. In sepsis, complement C3 components are rapidly consumed, which delays the physiological age-dependent increase observed in healthy foals.

65
Q

What is the shock organ of the horse?

Symptoms?

And Major mediators?

A

to complete…

66
Q

What is a type I hypersensitivity?

A

Immediate Hypersensitivity
Results from IgE attached to mast cell (preclude earlier from Th2 response) is cross-linked by antigen = Degranulation of mast cell = Acute inflammation (anaphylaxis)

67
Q

What is the major blood group system in horses?

A

AaCa

68
Q

Is cross-matching essential in horses?

A

yes, because the horse have a variety of blood groups and antibodies.

69
Q

What is Type II hypersensitivity?

A

Cytotoxic Hypersensitivity
Antibody-mediated = Antibodies and complement destroy normal cells
IMHA, incompatible blood transfusion

70
Q

What is Type III hypersensitivity?

A

Immune Complex Formation
Soluble antigens and antibodies combine to form immune complexes that can bind with complement and get stuck in “filter” areas (capillaries, joints, kidneys) = Activates neutrophils = Inflammation/tissue destruction

Glomerulonephritis and Polyarthritis

71
Q

What is Type IV hypersensitivity?

A

Delayed hypersenstivity
3 types: Th1 cells (activated MPs), Th2 cells (activated eosinophils, IgE), Cytotoxic T cells activation

Allergic contact dermatitis (Stevens-Johnson syndrome)

72
Q

What is the purpose of Coomb’s test?

A

To detect antibodies and complement on RBCs

73
Q

What does the regent for the Coomb’s contain?

A

Anti-IgG, anti-IgM, and anti-C3 (species specific)

74
Q

What is the prozone effect?

A

Relative excess of antiglobulin in relation to antigen (Ig or C3 on RBCs) at lower antisera dilutions resulting in decreased cross-linking of RBCs causing failure to agglutinate at low antisera dilutions

75
Q

What helps to increase the sensitivity of Coomb’s test?

A

Use of monovalent reagents, increased dilutions of antiglobulin to avoid a prozone effect, and testing at 4C

76
Q

What is the MOA of glucocorticoids?

A
  • Bind to cytosolic glucocorticoid receptor (GR), translocate to nucleus and binds to specific DNA sequence (glucocorticoid responsive elements) - enhance and inhibit transcription of genes
  • Anti-inflammatory: Stabilization of cell membranes of granulocytes, mast cells, and monocytes-MP, inhibition of phospholipase A2 (prevent release of arachidonic acid metabolites - COX and LOX pathways)
  • Prevent release of cytokines IL-1 and IL-6 = proinflammatory
  • Effects on complement and RAPID downregulation of Fc receptor expression on MP (reducing phagocytosis of opsonized RBCs and plts), esp with IM dz
77
Q

What is the MOA of azathioprine?

A
  • Cytotoxic synthetic imidazole derivative of 6-mercaptopurine (6MP) - thiopurines that interfere with purine synthesis = BAD nucleotides = NO DNA or RNA made, mitosis and cell metabolism is disrupted
  • “Lead-in “time of 11 days prior to clinical effects, can have lag period for up to 3-5 weeks
  • Cell-Mediated Immunity - Reduction in lymphocytes and T cell-dependent antibody production
  • Synergistic effects with steroids, allows for rapid taper of steroids (“steroid-sparing effect”)
78
Q

What are the 4 major side effects of azathioprine?

A
  • Myelosupression
  • Acute pancreatitis
  • Hepatopathy
  • Gastrointestinal Distress
79
Q

What immunosuppressant is there a documented breed variation?

A

to complete… Azathioprine:

  • Converted in liver (and other tissues) to 6MP
  • Thiopurine methyltansferase (TPMT) - enzyme in metabolism of 6MP
  • Measure it in RBCs
  • Variable in TPMT levels correlated with clinical outcomes in humans (high level = reduced efficacy; low level = risk of bone marrow toxicity
  • Document breed variations (Low levels in Giant Schnauzers, thus watch for toxicity, and high levels in Alaskan malamutes)
80
Q

What is the MOA of cyclophosphamide?

A
  • Cytotoxic alkylating agent, cross-links DNA, thus preventing separation
  • Suppresses CMI and humoral immunity
81
Q

Name 2 side effects of cyclophosphamide?

A
  • Hemorrhagic cystitis
  • Myelosupression
82
Q

What is the MOA of cyclosporine?

A

VERY POTENT T CELL INHIBITOR *Blocks transcription of genes required for T cell activation - IL-2 production is blocked *

Binds to cyclophilin (high concentration in cytoplasm of T cells) to form complex that prevents activation of calcineurin (that normally occurs when T cell receptor engages an antigen and triggers influx of Ca into cell)

Normally calcineurin acts as nuclear factor to induce cytokine gene transcription

Reduced IL-2 production = reduced clonal proliferation of T cells, and thus B cells

83
Q

Name possible side effects of cyclosporine?

A

Gastrointestinal signs (transient)

SERIOUS opportunistic infections

Emergence of neoplasia

Gingival hyperplasia

84
Q

What is the MOA of human IV Ig?

A

Competitively inhibits the binding of K9 IgG to monocytes by saturation of Fc receptors = prevents phagocytosis of antibody-coated RBCs and platelets

Use in IMHA and IMTP

85
Q

What is the MOA of danazol?

A
  • Synthetic Androgen
  • Downregulates MP Fc receptor expression
  • Reduced antibody binding to RBCs
  • Stabilizes RBCs membranes
86
Q

What is the MOA of vincristine for IMTP?

A
  • Low doses to increase platelet counts by stimulating megakaryocytes and impairs phagocytosis of opsonized platelets by impairing microtubule assembly MP
  • Unknown effect on platelet function
87
Q

What is the MOA of leflunomide?

A
  • Isoxazole immunomodulating drug
  • Primary metabolite - REVERSIBLY inhibits dihydro-orotate dehydrognease (RATE LIMITING ENZYME in de novo pyrimidine synthesis)
  • High concentrations = Inhibits cytokine and growth factor receptor-associated tyrosine kinase activity
  • T and B cell proliferation inhibited
88
Q

What are the potential side effects of leflunomide?

A
  • Hepatotoxicity
  • Myelotoxicity
89
Q

What is the MOA of mycophenolate?

A
  • Metabolized in plasma and liver to MYCOPHENOLIC ACID (MPA)
  • Reversible inhibitor of inosine monophospahte dehydrogenase (IMPDH) - KEY ENZYME in purine biosynthesis
  • Essential for lymphocyte proliferation (T and B cells proliferation, differentiation of Tc Cells and antibody production)
90
Q

Which immunosuppressive drug interferes with pyrimidine synthesis?

A

Leflunomide

91
Q

Which immunosuppressive drug interferes with purine synthesis?

A

Azathioprine

Mycophenolate

92
Q

How quickly can mycophenolate work?

A

Parenteral form - RAPID inhibition of IMPDH and thus immunosuppression - 2-4 hours after dosing (FAST!!)

93
Q

What is the MOA of lipsome-encapsulated clodronate?

A
  • Bisphosphate (management of hypercalcemia associated with Vit B intoxication)
  • Preferentially phagocytosed by MP and dendritic cells - APOPTOSIS
  • Induced killing in splenic MP and dendritic cells
  • Inhibits clearance of opsonized RBCs in normal dogs
  • ROLE: Treat antibody-mediated cytopenias where MP are key
  • Stops RBC and platelet destruction while gaining time for slower-acting agents
94
Q

What is the mode of inheritance and signalment of horses with severe combined immunodeficiency (SCID)?

A
  • Autosomal recessive.
  • Arabian foals 1-3mo.
  • Reported in one Caspian foal.
95
Q

Describe the pathophysiology of SCID.

A
  • Frameshift mutation in the gene encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs).
  • Affected foals lack functional B and T lymphocytes and thus cannot mount an adaptive IR against microorganisms.
  • All other innate defence mechanisms are present e.g. complement, NK cells, neutrophils and macrophages.
  • CSx develop at 1-3mo as maternal ABs wane and inc exposure to pathogens –> generalised infection.
96
Q

Describe the clinical signs and prognosis of SCID.

A

URT infections and pneumonia are most common presenting complaints, with diarrhoea less commonly obs.

Adenoviral pneumonia seen in approx 2/3 of SCID foals.

Pneumocystis carinii, Rhodococcus equi, Streptococcus sp. and Cryptosporidium sp. also commonly isolated.

Foals may initially respond to AB tx and supportive care but succumb to overwhelming infection by 2-5mo.

97
Q

How is SCID diagnosed in foals?

A

Compatible history and clinical signs.

Severe lymphopenia

98
Q

What are the characteristic features and signalment of horses with combined variable immunodeficiency (CVID)?

A
  • Characterised by late-onset recurrent bacterial infections, hypo- or agammaglobulinemia, progressive B cell lymphopenia or depletion, and poor response to vacc.
  • The majority of equine cases present in adulthood.
  • Many different breeds and both sexes have been affected.
  • No regional geographical distribution.
99
Q

Describe the most common presenting clinical signs and prognosis in horses with CVID.

A
  • Recurrent fever and pneumonia most common.
  • Infections of nervous system, GIT, gingiva, sinuses, liver and skin have also been reported.
  • Some horses have been managed for 1–5y on continuous or intermittent antimicrobial and immunoglobulin therapies.
  • Majority are euthanised.
100
Q

How is CVID diagnosed in horses?

A

Compatible history and clinical signs.

Intermittent or persistent lymphopenia

101
Q

What is the proposed pathogenesis of CVID?

A

Horses with CVID demonstrate impaired B cell production in the bone marrow.
Expression of essential B cell genes, including transcription factors and cell receptor genes, was measured using real-time RT-PCR.
Results of this study suggest that B cell dev is impaired at the transition between pre-pro-B cells and pro-B cells.
The mechanism of B cell depletion and the initial trigger for loss are still under investigation.

102
Q

What is the mode of inheritance and signalment of horses with foal immunodeficiency syndrome (a.k.a. FIS, Fell Pony Syndrome)?

A
  • Autosomal recessive trait.
  • Estimated to affect 10% of Fell and 1% of Dales foals
103
Q

Describe the pathophysiology of FIS.

A

low PAX5 gene expression in the bone marrow was detected. This gene is essential for B cell commitment and development, as well as B cell survival in peripheral tissues.

To summarize, FIS-affected foals appear to be born with erythroid precursors and B cells in the bone marrow, suggesting productive fetal hematopoiesis. Postnatal development of progressive anemia and B cell lymphopenia coincides with erythroid and myeloid dysplasia and severe erythroid hypoplasia in the bone marrow, and is associated with decreased expression of at least one gene responsible for B cell development.

Recently, a genetic mutation was identified in foals affected with FIS.17 The sodium/myoinositol cotransporter gene (SLC5A3) demonstrates a single nucleotide polymorphism that results in an amino acid substitution, which likely alters the function of SLC5A3.

Although the mechanism has not been elucidated and a causal relationship between the SLC5A3 mutation and FIS has not been established, dysfunction of this protein may lead to erythropoiesis failure and myeloid hypoplasia. It is possible that other genomic mutations may be responsible for the FIS phenotype, and further investigation is ongoing.

104
Q

Describe the clinical signs and prognosis of FIS.

A

Foals with FIS are generally normal at birth.

Dev CSx that may include weakness, inappetence, poor growth, nasal discharge, diarrhoea and pale MMs at 2-6wk.

Invariably fatal by 3mo.

105
Q

How is FIS diagnosed?

A

CBC: severe, progressive anaemia, lymphopenia and neutrophilia.

WBC phenotyping: B cell lymphopenia.

Expect dec serum Ig, but hypoglobulinemia is not a consistent finding given presence of maternal colostral Ab.

Necropsy: small numbers of erythroid precursors in the bone marrow, a small thymus, lack of secondary lymphoid follicles or germinal centers, and peripheral ganglionopathy.

106
Q

Describe the characteristic feature and aetiology of selective IgM deficiency in horses.

A

Characterised by absent or decreased serum IgM levels with normal or elevated levels of other Ig classes.

Unknown if primary or secondary in foals.

Genetic basis suspected but not proven.

In people can be secondary to neoplasia, immunologic diseases and gluten-sensitive enteropathies.

107
Q

Describe the three presentations of selective IgM deficiency that have been reported in horses.

A
  1. Foals w severe infectious pneumonia, arthritis or enteritis –> death prior to 10mo.
  2. Foals w history of repeated infections that respond to antimicrobials but recur when tx is stopped; survive 1-2yr.
  3. Horses 2-5yo at time of dx; not recurrent infection; 50% have lymphosarcoma.

Most freq reported in QHs and Arabians.

108
Q

Describe clinicopathologic findings in horses with selective IgM deficiency.

A

IgM levels more than two standard deviations below the age-specific mean (repeat test to prove persistently low).

CBC/MBA may reflect infection or inflammation depending on underlying infectious process and organ systems involved.

109
Q

Describe the pathophysiology of selective IgM deficiency in horses.

A

Unknown whether IgM is low because of decreased production, hypercatabolism or loss.

In one horse with lymphosarcoma, suppressor activity was identified in the neoplastic cells.

Lymphoid tissue is grossly and histologically normal.

110
Q

Outline the treatment and prognosis of selective IgM deficiency in horses.

A

Unfavourable long-term prognosis, however rare cases recover.

Most horses succumb to infection despite appropriate antimicrobial therapy.

Plasma may be beneficial, but low IgM concentration in commercial plasma and short half-life.

111
Q

Define Purpura Haemorrhagica.

A

It is a noncontagious, immune-mediated vasculitis of horses that is characterised by subcutaneous oedema of the head, ventral abdomen, and limbs and by petechial haemorrhages of the MMs.

112
Q

Describe the aetiology of purpura haemorrhagica.

A

PH most often occurs as a rare complication of Strep equi infection (1-17% of cases, CSx appear 1-2wk post apparent recovery) but can also develop after infection with other bacterial and viral organisms, particularly those that cause formation of purulent or necrotic foci.

Also reported after vaccine or drug admin and idiopathically.

Prerequisites for the dev of PH: a large amount of antigenic material and an exaggerated immune response.

113
Q

Describe the pathophysiology of purpura haemorrhagica.

A
  • Strangles –> Ab prod –> bind to circ M-like protein to form limited quantities of large Ag-Ab complexes. Because of their size, these complexes are easily removed by the reticuloendothelial system and do not cause problems.
  • When quantity of Ag greatly exceeds that of circulating Ab much smaller immune complexes form → not removed by the RES → travel through the general circ and are deposited in endothelial BMs of capillaries and other small blood vessels of the skin.
  • Ag-Ab complexes activate complement → as neut penetrate the vessel walls and phagocytose the complexes, they release lysosomal enzymes and radical O2 species into their immediate environment → compromise the integrity of the vessel walls and allow proteins, fluid, electrolytes and erythrocytes to leak into the ECF.
  • Classified as Type III hypersensitivity reaction (Ag/Ab prod); somewhat unusual in that IgA appears to be the primary Ig involved vs IgG in most Type III reactions.
  • Although the capillaries, arterioles, and venules of the skin are most commonly affected in PH, Ag-Ab complexes can also settle in a variety of organs (e.g., the lungs, kidneys, and liver), the GIT or skeletal muscle and can cause vascular inflammation and haemorrhage.
114
Q

What is the classic histopathologic lesion in the skin of horses with purpura haemorrhagica?

A

Characteristic histo finding is necrotising leukocytoclastic vasculitis distinguished by fragmented neutrophils and nuclear debris surrounding small blood vessels.

Oedematous blood vessel walls, dermal and SC haemorrhage, inflammation, and thrombi may be visible.

115
Q

Describe the clinical presentation of horses with purpura haemorrhagica.

A

Commonly affects young adult horses (has occurred in yearling and geriatrics). No breed or sex predilection.

Affected horses most often initially present with depression and anorexia followed by urticaria and swelling around the nares → quickly progresses to severe SC oedema of the head, ventral abdomen and limbs.

Oedema is pitting, nonpruritic, sharply demarcated, warm or cool and can cause significant discomfort.

Dyspnoea can occur: URT/LRT swelling or pul oedema.

Dysphagia is another complication.

Oedema on the limbs can –> skin necrosis, lameness.

Petechial or ecchymotic haemorrhages of the mucosal, nasal, and conjunctival membranes are common.

Epistaxis is less commonly reported.

Tachycardia occurs frequently.

Many horses demonstrate concurrent signs of strangles, such as lymphadenopathy, draining abscesses, coughing, and nasal discharge. Pyrexia may or may not be present.

Signs of specific organ disease can occur if the immune complexes are deposited in sites other than skin:

  • Haematuria associated with glomerulonephritis.
  • Severe colic, dxa from ulcerative necrosis of GI mucosa.
  • Lameness due to polyarthralgia, synovitis, or joint infect.
  • Immune-med myopathies, incl a particularly severe and usually fatal form called infarctive purpura haemorrhagica → muscle swelling, stiffness, or colic and, at necropsy, were found to have widespread muscle infarctions as well as multifocal sites of pulmonary haemorrhage.
  • Thrombophlebitis, cellulitis, and pneumonia are further complications of purpura haemorrhagica.
116
Q

Describe treatment of purpura haemorrhagica.

A

Removal of the antigenic stimulus (if identified): drainage of abscesses, exploration of wounds, flushing GPs; penicillin reccom due to Strep or gram –ve if warranted.

Suppressing the immune response by using glucocorticoids e.g. 10d dex, 2-3wk pred.

NSAIDs may be beneficial b/c of their ability to alter leukocyte chemotaxis and prevent leukocyte adhesion to the damaged endothelium, which may avert further damage to vessel walls.

Supportive care: IVFT, nutritional support, plasma, hydrotherapy, bandaging, light exercise, InO2, trach.

117
Q

Describe the prognosis for horses with purpura haemorrhagica.

A

Early recognition and tx improve the Px for survival.

Px for recovery is fair to good and generally depends on whether the horse sustains additional internal organ injury from the circulating antigen-antibody complexes.

Poor Px indicators incl fever, respiratory distress, pleural effusion or pulmonary oedema, and sudden onset of dxa.

Most common reasons for euth or death incl dev of secondary complications eg. renal disease, colic, rhabdomyolysis, and laminitis.

Typical PM findings in these animals are significant haemorrhage and infarcts in the GIT and the kidneys.

ECEIM (16 decks)

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