Immunology: 3 Flashcards

Question

Meachanism of spread of EHV1 in the body

Answer 1

EHV1 infection is rhinopneumo- nitis caused by a localized infection of the nasopharyngeal mucosa. In almost all cases, a cell-associated viremia alsooccurs in lymphocytes, but in most infected horses this does not result in disease. However, in some cases, viremia is associated with infection of endothelial cells, and in the pregnant mare vascular damage to the uterus and placenta may lead to abortion.Similarly, infection of the vascular endothelium in the central nervous system results in neurologic disease.

Answer 2

ability of different viral strains to infect different cell typesand cause syncytia (fusion of an infected cell with neighboring cells leading to formation of multinucleate enlarged cells) formation

Answer 3

Several nematode parasites infect the equine lung. These include migrating stages of Strongyloides westeri and Parascaris spp. en route to the small intestine. Migrating stages of aberrant parasites, such as Habronema sp., Draschia megas- toma, and Strongylus spp., which induce granulomatous foci in the lung parenchyma, and adults and larvae of the lungworm Dictyocalus arnfieldi, which inhabit the bronchi, also occur.

Answer 4

A number of helminth parasites, including Parascaris spp., stimulate intestinal smooth muscle hyperplasia.

Answer 5

a type 2 T-helper cell cytokine response consisting of interleukins (ILs) IL-4, IL-5, IL-9, and IL-13. IL-4 and IL-13 induction of the Stat6 pathway is cen-tral to most of the resulting responses. There is a consistent mastocytosis and eosinophil infiltration of the intestine.

Answer 6

Onchocerca cervicalis infections (microfilariae in the skin) vector: culicoides spp Focal, alopecic, depigmented, pruritic lesions are often seen in infected horses Lesion development is associated with immune-mediated killing of microfilariae in the skin. sensitive to macrocyclic lactone anthelmintics [adults can be found in the nuchal ligament - normally asymptomatic - cannot be killed by Ivermectins]

Answer 7

Strongyloides westeri: Mares remain infected with arrested third-stage larvae, which subsequent to foaling are transmitted to the foals in milk starting at 4 days postpartum.

Answer 8

The cell walls and membranes of bacteria contain various proteins and polysaccharides with characteristic, often repeating, molecular structures. These pathogen-associated molecular patterns (PAMPs) include **lipopolysaccharides (LPSs), peptidoglycans, lipoteichoic acid, and flagellins.** Other PAMPs include viral nucleic acids and unmethylated bacterial **cytosine-guanosine dinucleotides (CpG).** PAMPs are recognized by pattern recognition receptors found on cells of the immune system, particularly those cells involved in the initial encounter with invading microbes. These “sentinel cells” include **macrophages, dendritic cells, and mastcells,** _with macrophages being the most important for initiating the inflammatory response._ * **toll-like receptors (TLRs),** * **retinoic acid–inducible gene–1 (RIG-1)–like receptors, and n** * **ucleotide-binding oligomerization domain–like receptors.**

Answer 9

Injured cells release products collectively termed damage-associated molecular patterns (DAMPs) that bind TLRs on macrophages and other cells leading to the production of proinflammatory cytokines that augment the inflammatory process.

Answer 10

Resident macrophages that encounter the invader initiate the inflammatory response through the production of proinflammatory cytokines such as interleukin- 1 (IL-1), IL-6, and tumor necrosis factor–alpha (TNF-α)

Answer 11

Many of the effects of IL-1 are mediated through its capacity to increase the production of other cytokines, such as granulocyte colony-stimulating factor (G-CSF), TNF-α, IL-6, and platelet-derived growth factor (PDGF). IL-6 is responsible for the increased production of acute phase proteins by hepatocytes, including complement proteins, C-reactive protein, and serum amyloid A (SAA). Activates T cells, Chemotactic for neutrophils, Activates neutrophils Induces fever, Activates B cells, Enhances NK cell killing Fibroblast growth factor Stimulates collagen production Stimulates PGE synthesis Stimulates keratinocyte growth Stimulates bone resorption Activates osteoclasts Induces IL-6 production

Answer 12

During viral infections, **intracellular pattern recognition receptors (such as RIG-1) bind to viral PAMPs** and induce the **production of type I interferons (IFNs)**, including IFN-α and IFN-β. These are produced in virus-infected cells within hours and i**nhibit viral replication** through various mechanisms. In addition, **natural killer (NK) cells are capable of lysing virus infected cells via recognition of different types of receptors on the surface of infected cells**, as well as recognizing cells expressing fewer major histocompatibility complex molecules, the expression of which can be downregulated by viral infection. Finally, NK cells have surface Fc receptors that can bind the Fc portion of antibodies bound to the surface of infected cells and subsequently kill the infected cell through the process of antibodydependent cellular cytotoxicity

Answer 13

The complement system (part of innate response) consists of over 30 different plasma proteins that are produced primarily in the liver. This complex interacting series of proteases and their substrates results in the production of physiologically active intermediaries that can damage membranes, attract neutrophils and other cells, increase blood flow and vascular permeability, and opsonize bacteria and other particles for phagocytosis

Answer 14

**lectin pathway** is initiated when soluble carbohydrate-binding proteins bind to carbohydratestructures on microbial surfaces. Proteases associated with these carbohydrate binding lectins then initiate the cleavage of complement components and activate the pathway. The **classical pathway** involves the binding of C1q to antibodies already bound to the surface of a microbe. Bound C1q is proteolytic and cleaves other complement components activating the pathway. The activation of complement via the **alternate pathway** does not involve antibodies. Instead, certain microbial products stimulate the association of factor D, a proteolytic enzyme, with the complex of factor B and C3b leading to the formation of C3 convertase and its deposition on the microbial surface. All three pathways converge with the generation of C3 convertase and the cleavage of C3. Soluble C3a, producedby the cleavage of C3 by the C3 convertases, can bind to mast cells causing them to degranulate and is thus referred to as an anaphylatoxin, as is C4a. C3b serves as an opsonin for C3b receptor-bearing phagocytic cells. C3b is also required for the formation of the membrane attack complex by the terminal complement components, C5 through C9. In this process C5 is cleaved and C5a is generated, which, along with C3a, is a chemoattractive factor for neutrophils and monocytes. C5b forms a complex with C6, C7, and C8 on cell surfaces. This leads to the insertion and polymerization of C9 that forms a pore in the membrane leading to cell lysis.

Answer 15

Prostanoids are lipid mediators that regulate the inflammatory response.The prostanoids include the **prostaglandins (PGs), leukotrienes (LTs), and prostacyclin (PGI2)**, and they are the **product of cyclooxygenase cleavage of arachidonic acid** followed by endoperoxidation. The major sources of prostanoids in acute inflammation are the **phagocytes, endothelial cells, and platelets.**

Answer 16

Prostanoid production depends on the activity of the two isoforms of the cyclooxygenase(COX) enzymes within cells: * *COX-1,** which is present in most cells and its expression is generally constitutive, and * *COX-2,** for which expression is low or undetectable in most cells but its expression increases dramatically on stimulation, particularly in cells of the immune system.

Answer 17

PGE2 is considered proinflammatory because it promotes * **vasodilation by activating receptors on vascular smooth muscle** and * **increases vascular permeability indirectly by enhancing the release of histamine** and other mediators from tissue leukocytes such as mast cells. * **responsible for fever production**. However, as inflammation progresses, **PGE2 synthesis by macrophages is enhanced as a result of increased expression of COX-2** and PGE-synthase, and the resulting increased levels of PGE2 * **inhibit leukocyte activation,** * **inhibit mast cell degranulation**, and * **relax smooth muscle contractions** * In the lung, PGE2 promotes bronchodilation. Thus in these situations PGE2 may be considered antiinflammatory.

Answer 18

Chemokines are chemotactic cytokines. These are soluble proteins produced by host cells that **induce the directional migration and activation of leukocytes, as well as other somatic cell types**, and thus play major roles in the inflammatory response. The chemokine CXCL8 (previously known as IL-8) plays a central role in the migration of neutrophils, including equine neutrophils.

Answer 19

Neutrophil adherence is a two-step process first involving * endothelial cell surface molecules known as **selectins**. endothelium exposed to _leukotrienes, platelet activating factor (PAF), IL-1, complement protein C5a, histamine, LPSs, TNF-α, or other mediators_ express **P-selectin**. =\> **P-selectin** mediates the process in which neutrophils initially interact with the endothelial surface in a process known as _“rolling”_ (after a few hours: E-selectin) _Endothelial selectins function by binding to carbohydrate ligands present on the leukocyte surface._ In the case of neutrophils, the ligand is **sialyl-LewisX.** * then **tight binding of integrins** on the neutrophil surface to intracellular adhesion molecules on the endothelial cell surface. Leukocyte integrins are proteins and include functional antigen–1 (LFA-1) and complement receptor type 3 (CR3) * then **migration**

Answer 20

Acitvated neutrophils will actively phagocytose microscopic invaders and attempt to destroy them using **reactive oxygen products generated via a nicotinamide adenine dinucleotide phosphate(NADPH)-oxidase–dependent respiratory burst**.

Answer 21

production of IFN-α or IFN-β by macrophages production of IFN-y by NK cells

Answer 22

Deactivation signals include **PGE2, cortisol, IL-10, and transforming growth factor–β (TGF-β).** Some of those chemotactic agents responsible for initiating the response (CXCL8, FMLP, C5a, LTB4, and PAF) also serve to downregulate its intensity by inducing the shedding of IL-1 receptors from neutrophils

Answer 23

* Antibodies are produced by B lymphocytes, **small lymphoid cells characterized by the cell surface expression of immunoglobulin** molecules. * B cells represent less than 15% of the circulating peripheral blood mononuclear cells but are p_resent in higher proportions in lymph nodes and the spleen._ * B cells are derived from the fetal liver and bone marrow of mammals, developed from a lymphoid stem cell derived from the pluripotent stem cell. * Under the influence of various cytokines produced by bone marrow stromal cells, the B-cell precursor undergoes its _3-day development into a mature B_ _cell_. * On stimulation with a specific antigen (f.e. by a macrophage presenting an antigen), B cells d_ifferentiate into **plasma cells** that produce enormous quantities of a specific_ _antibody **(=gamma globulines)** or **memory cells.**_

Answer 24

The T lymphocyte is also derived from the multipotent stem cell and lymphoid precursor in the bone marrow, though its subsequent development into the mature T cell occurs in the thymus.

Answer 25

**B cell surface bound immunoglobulin, also known as antibody.** An immunoglobulin molecule is composed of t_wo identical light chains_ and _two identical heavy chains_ that form a disulfide-linked Y-shaped molecule * The **light chain** can be divided into two domains, a conserved carboxy-terminal domain and a highly variable amino-terminal domain. * Analysis of heavy chains reveals a similar domain structure with the amino-terminal domain being highly variable and the presence of three constant domains. =\>The antigen-binding region of an immunoglobulin molecule is formed by the association of the amino ends of a light and a heavy chain, and the carboxyl end of the heavy chain determines the isotype of the molecule. Similar to most species, five different immunoglobulin isotypes (classes) have been identified in the horse: IgM, IgD, IgG, IgE, and IgA

Answer 26

Surface IgM is found on naive, activated, and memory B cells. Secreted IgM represents the **major antibody produced during a primary response.** IgM efficiently mediates agglutination, neutralization, opsonization, and complement activation.

Answer 27

IgD = Antigen receptor of naive B lymphocytes.

Answer 28

The _principal immunoglobulin found in plasma representing up to 80% of the total immunoglobulin concentration._ The major functions of IgG include opsonization and neutralization reactions. 7 subclasses * IgG1, IgG3, and IgG4/7 are effective in fixing complement, and * IgG1, IgG4/7, and IgG3/5 bind Fc receptors so they can function as opsonins and mediate antibody-dependent cellular cytotoxicity. * IgG6 and IgG5 may play an important role in exotoxin neutralization and immunity to parasites.

Answer 29

Most IgE is found associated with the surface of mast cells and basophils and only very small amounts are present in the plasma. The cross-linking of two IgE molecules with specific antigen results in the **degranulation of the mast cells and basophils.** Thus IgE is the primary antibody responsible for **type I hypersensitivity reactions** and **appears to play a central role in immunity to parasites.**

Answer 30

The **most abundant antibody in secretions** (tears, mucus, saliva, colostrum, etc.) _IgA antibodies can be neutralizing_ but do not fix complement efficiently nor do they have efficient opsonization activity.

Answer 31

T lymphocytes can be differentiated from B lymphocytes in that they _do not express surface immunoglobulins_ but instead express the **T-cell receptor (TCR)** (involved in antigen-specific recognition). T cells also express another surface molecule called CD3. (The designation CD stands for cluster of differentiation) 2 types of TCRs: * T cells are **mostly αβ T cells** * fewer than 5% of all T cells expressing the **γδ receptor.** T cells **only recognize processed antigen bound by antigen-presenting molecules** **_(MHC I+II)_** on the surface of antigen-presenting cells (APCs).

Answer 32

The five proteins of the CD3 complex are involved in signal transduction following TCR binding to antigen. (phosphorialted in response to TCR stimulation)

Answer 33

Mature T lymphocytes can be further divided into two distinct populations on the basis of their expression of either the **CD4 or CD8 molecule**. * cells expressing CD8 are typically **cytotoxic effector cells** (cytotoxic T lymphocytes [CTLs]), **_react to MHC I_** * cells expressing CD4 are typically **helper cells** that produce cytokines that enhance antibody and cell-mediated immune responses. **_react to MHC II_** Whereas the T lymphocytes in the periphery express either CD4 or CD8, **cortical thymocytes (immature T cells in the thymus)** **express both antigens**. During maturation in the thymus, these cells convert to either CD4+ or CD8+ cells or they are eliminated.

Answer 34

T cells only recognize processed antigen bound by antigenpresenting molecules on the surface of antigen-presenting cells (APCs). **These antigen-presenting molecules are glycoproteins encoded by genes within a large gene cluster called the major histocompatibility complex (MHC)** **MHC = group of genes that encode proteins on the cell surface that have an important role in immune response: their main role = antigen presentation** *Determines whether transplanted tissue is histocompatible or not.*

Answer 35

* **intracellular antigens** are processed via the endogenouspathway and are associated with **MHC I molecules** that present them to CD8+ **cytotoxic T cells**, * **extracellular antigens** are processed via the exogenous pathway and are associated with **MHC II molecules** that present them to **CD4+ helper** T cells * endocytosed antigens, such as that phagocytosed by a macrophage, are degraded into peptide fragments within a phagolysosome compartment. Processed peptides then bind with the MHC II molecule. The MHC II molecule is then transported and expressed on the cell surface for subsequent presentation to the **helper T cell.** The immune system contains a distinct group of professional antigen-presenting cells called **dendritic cells**

Answer 36

The protein _tyrosine kinase associated with the cytoplasmic tail of CD4_ (or CD8) phosphorylates the cytoplasmic regions of the **CD3 proteins** (associated with the TCR) in regions known as immunoreceptor tyrosine–based activation motifs (ITAM). A series of subsequent phosphorylation events ultimately leads to the **release of stored Ca from the endoplasmic reticulum**. The increase in intracellular Ca levels and the**activation of protein kinase C**leads to the**phosphorylation of various transcriptional factors that regulate the expression of the genes for various cytokines and/or their receptors.**

Answer 37

activated T-cells

Answer 38

**Naive T lymphocytes** take the most common route, which involves entry into the lymph node by extravasation from the high endothelial venule (HEV) and return to the peripheral circulation via the efferent lymphatic. This allows rapid repeated circulation of naive lymphocytes through lymph nodes where there is the greatest chance of exposure to their specific antigens. naive lymphocyte expresses _L-selectin to bind to endothelium_ -\> lost when activated **Memory lymphocytes** leave the bloodstream in peripheral vascular beds, particularly in inflamed tissues, and return to lymph nodes via afferent lymphatics. This leads to the exposure of primed memory lymphocytes to the most likely early sites of antigenic encounter and allows for an early response to recall antigens.

Answer 39

mucosal-associated lymphoid tissue (fe Payer patches and pharyngeal tonsils) ## Footnote MALT consists of lymphoid follicles containing IgA-committed B cells, surrounded by interfollicular T-cell areas with APCs and HEVs, with an overlying follicle-associated epithelium (FAE).

Answer 40

* Available studies indicate that innate immunity is intact in foals and leads to functional neutrophil responses similar to those in adults but that **adequate levels of immunoglobulins and complement with opsonizing activity are critical** (colostrum needed) * epitheliochorial placentation in horses, transfer of maternal antibodies does not occur in utero, and foals are born essentially agammaglobulinemic. * also, helper **T-cytokine expression/production and T-cell responses are quantitatively lower** than those of adult horses.

Answer 41

When foals are vaccinated with antigens against which they have no passively transferred antibody, normal antibody responses have been documented from _at least 3 months of age_. In colostrum-fed foals, **serum IgG concentration falls to its lowest level at 1 to 2 months of age** _as a result of catabolism of maternally transferred immunoglobulin_, subsequently _rising toward adult levels as a result of endogenous immunoglobulin production_. *Some maternal antibodies stay up to several months making an early vaccination ineffective!*

Answer 42

The half-life for maternal IgG in foals is estimated at **20 to 30 days.**

Answer 43

**antibody-mediated hypersensitivity diseases (types I, II, and III) are immediate** in onset _if preformed antibody exists in circulation or tissues_, with some variation in time course dependent on the antibody isotype involved. **Cell-mediated hypersensitivity diseases (type IV) are delayed**, _even in sensitized individuals_, **for 1 to 3 days**, while effector cells are recruited to the site of antigen exposure

Answer 44

mediated by **IgE antibody** specific for allergens, which are extrinsic antigens normally not recognized by the healthy immune system. IgE is predominantly found in tissues, where it is **bound to mast cells through the high-affinity IgE receptor, which is called FcεRI (basophils and eosinophils also have those receptors when activated)** _TH2 response (too much compared to Th1)_ _f.e. penicillin allergy in humans_

Answer 45

Some individuals are _predisposed to IgE-mediated hyperactivity to a wide variety of environmental allergens_, and this condition is termed atopy. Affected individuals have high levels of IgE in the blood and increased eosinophil populations.

Answer 46

Histamine causes an increase in local blood flow and capillary permeability

Answer 47

**Mast cell degranulation** causes an immediate allergic reaction within seconds, but there is also a sustained late-phase response that develops over up to 8 to 12 hours due to **recruitment of TH2 lymphocytes -\> eosinophils, and basophils. (**activation of the latter causes them to exprime FcERI)

Answer 48

This form of hypersensitivity disease occurs when the **causal antigen is associated with cells or tissue components** of the body, and there is an **IgG antibody response to this antigen**. _Phagocytes, or other cells expressing Fcγ receptors_, mediate destruction of the affected tissue, or removal from the circulation by the reticuloendothelial system in the case of antibody- positive erythrocytes or platelets. f.e. Blood transfusion reactions, neonatal isoerythrolysis, immunemediated hemolytic anemia and thrombocytopenia are examples of drug-associated type II hypersensitivities.

Answer 49

Type II hypersensitivity: In the case of the horse, penicillin is an established cause of **hemolytic anemia.** Diagnosis can be accomplished using a **Coombs test.** _Penicillin binds to the erythrocyte surface and is targeted by antipenicillin antibodies of the IgG isotype._ Interestingly, quite large numbers of horses have antipenicillin antibodies of the IgM isotype, but this does not lead to disease.

Answer 50

In type III hypersensitivity the antigen is soluble and present in the circulation. _Disease results from formation of antibodyantigen aggregates or immune complexes_ . Although immune complexes are generated in all antibody responses, they are generally harmless. Large complexes fix complement and are removed from circulation by the reticuloendothelial system. However, **small complexes can form at antigen excess**, **and these can deposit in blood vessel walls and tissues where they ligate Fc receptors on leukocytes**, causing an inflammatory response, increased vascular permeability, and tissue injury. f.e. glomerulonephritis in equine infect anemia, Purpura hemorrhagica following Streptococcus equi infection

Answer 51

**Cell-mediated** type IV hypersensitivities cause _delayed hypersensitivity reactions_. A variety of cutaneous hypersensitivity reactions are seen, such as the contact hypersensitivity seen after absorption of haptens such as pentadecacatechol in poison ivy (Efeu) or the local TH1 response seen in the diagnostic tuberculin reaction. When type IV hypersensitivity results in a _TH2 response the principal outcomes are eosinophil activation and recruitment such as in chronic asthma in humans._

Answer 52

= incomplete antigen can elicit an immune response only when attached to a large carrier such as a protein f.e. Penicilline causing hemolytic anemia

Answer 53

IgE production in horses does not occur before 9 to 11 months of age and does not reach adult levels before 18 months.

Answer 54

**Systemic anaphylaxis is a severe immediate type I hypersensitivity reaction mediated by IgE.** reported after administration of a wide range of compounds, including serum, vaccines, vitamin E–selenium preparations, thiamine, iron dextrans, and antibiotics, including penicillin. Target organs in experimental equine anaphylaxis are the lung and the intestine. **Cardinal signs:** Sudden dyspnea; hypotension, as evidenced by poor peripheral pulse character; rapid onset of urticaria; collapse

Answer 55

Hypotension: **Epinephrine** IM (0.01–0.02 mg/kg, equivalent to 4.5–9 mL of 1:1000 dilution of epinephrine for a 450-kg horse) if dyspnea and hypotension not severe --\> otherwise IV, side effects: tachyarrythmia, excitement, myocardial ischemia **Glucocorticoid therapy** during the acute phase will aid in preventing the late-phase reaction. ideally rapid-acting glucocorticoid: *prednisolone sodium succinate* (0.25–10.0 mg/kg intravenously), but *dexamethasone* may also be used (0.2–0.5 mg/kg intravenously).

Answer 56

mixed; incompletely understood, although accompanied by an increase in IgE

Answer 57

* type I * In some breeds a genetic predisposition based on an MHC II linkage has been demonstrated.

Answer 58

**jaundice foal agglutination** **test** * making 1-mL serial dilutions of the mare’s colostrum in saline (1:2–1:128), * adding 1 drop of the foal’s anticoagulated (EDTA) whole blood to each tube and mixing, centrifuging at medium speed (300–500 × g) for 2 to 3 minutes, * observing for agglutination of the red blood cell pellet by inverting the tubes. =\> If strong agglutination occurs at or above the 1:16 dilution (≥1:64 for mule foals), the foal should not be allowed to nurse the mare _during the first 36 hours._ -\> in affected foals: confirmation using a variation of the Coombs test

Answer 59

Equine recurrent uveitis (ERU), also known as moon blindness or periodic ophthalmia is a **type IV hypersensitivity reaction** =\> development of posterior and anterior synechiae, cataracts, lens opacities, secondary glaucoma, and blindness. Eyes of affected horses _contain IgG antibodies and autoreactive T cells specific for retinal antigen_s. potentially associated with the presence of **Leptospira**: _molecular mimicry between the Leptospira antigens and equine intraocular proteins =\> autoimmune reaction!_

Answer 60

Purpura hemorrhagica is an uncommon **acute type III hypersensitivity** (immune complex) disease in horses characterized by edema of the head and limbs; leukocytoclastic vasculitis; petechial hemorrhages in mucosae, musculature, and viscera; and sometimes glomerulonephritis. often associated with **infection with** **Strep equi** and **Corynebacterium pseudotuberculosis**

Answer 61

= tolerance break, f.e. * break in central tolerance occurs when self reactive B or T cells are not negatively selected during the maturation process in the bone marrow and thymus and are released into the circulation, * peripheral tolerance mechanisms exist to control autoreactivity. One of these peripheral tolerance mechanisms is the downregulation of self reactive T cells by **Tregs**. B cells have a higher probability of developing self reactivity than T cells. Thus many autoimmune diseases with known mechanisms involve autoantibodies. * Autoreactive lymphocytes may respond to self antigens due to _molecular mimicry_, f.e. Leptospira x ERU, thrombocytopenia x EIA

Answer 62

transfer of passive immunity, which is defined as a s**erum IgG concentration greater than 800 mg/dL**. Serum IgG concentrations less than 400 mg/dL and between 400 and 800 mg/dL have defined complete and partial FTPI

Answer 63

radial immunodiffusion (RID) assay

Answer 64

* *Severe combined immunodeficiency (SCID)** is a lethal primary immunodeficiency affecting Arabian foals, **characterized by failure to produce functional B and T lymphocytes** and resulting in the **complete lack of adaptive immune responses. ** vast majority of affected foals are Arabians, in which the condition is inherited as an **autosomal recessive trait** and results from a _lack of DNA protein kinase (DNA-PK) activity_ --\> V(D)J recombination does not occur =\> _developing T cells and B cells do not produce functional TCRs and BCRs_ and thus fail the positive selection process in the primary lymphoid organs.

Answer 65

* _persistent marked lymphopenia_ (usually less than 500/μL) and the _absence of serum IgM by RID_. If presuckle serum is unavailable for testing, serum IgM cannot be used as a diagnostic aid until the foal is older than 3 weeks. * definitive diagnosis: evaluation if homozygous for the defective SCID gene. (PCR amplification of a specific region of the DNA-PKcs gene) testing with whole blood, pulled hair, or cheek swabs * **post mortem:** hypoplasia of the spleen, thymus, and lymph nodes with the absence of any normal lymphoid architecture (life expectancy max 5 months, first signs of infection around 1-3 months of life)

Answer 66

* congenital syndrome caused by a SLA5A3 mutation leading to anemia, immunodeficiency (profound B-cell lymphopenia), and peripheral ganglionopathy * affected until very recently up to _10% of Fell and 1% of Dales foals_, respectively * diagnosis via PCR based DNA test

Answer 67

Common Variable Immunodeficiency is rare but should be suspected in adult horses with recurrent infections as described previously, hypogammaglobulinemia, B-cell lymphopenia, and failure to respond appropriately to vaccination. =\> B-cell depletion and inadequate antibody production caused by failure of B lymphocyte maturation in the bone marrow

Answer 68

**serum IgM concentrations persistently less than** 2 standard deviations below that of agematched controls (less than 15 mg/dL at 4–8 months; less than 25 mg/dL at greater than 8 months) **coupled with normal concentrations of IgG** (≥1000 mg/dL) and **a normal lymphocyte count.** **=\> exact gene unknown**

Answer 69

Although yet to be identified in foals, the **neonatal Fc receptor** (FcRn) transports maternal IgG from the intestinal lumen through enterocytes and into the systemic circulation in mice

Answer 70

less than 3000 mg/dL can be estimated by **specific gravity** or quantitated by **RID**

Answer 71

Lymphoma is often associated with IgM deficiency

Answer 72

Affected foals have _profound lymphopenia and generally die_, despite therapy. The immunodeficiency is thought to be due to _viral-induced lymphoid damage_, because necropsy reveals marked necrosis of lymphoid tissue in the thymus, spleen, and lymph nodes.

Answer 73

after crossing the cell membrane they _bind to cytoplasmic glucocorticoid receptors_. Once activated, glucocorticoid receptors are _transported to the nucleus where they bind to DNA and interact with other transcription factors_, resulting in the regulation of as many as 20% of the genes expressed in leukocytes: **↓ expression of cytokines, ↓ Phospholipase A2, cyclooxygenase type 2 =\>↓ Protaglandins, leukotrienes, ↓ Adhesion molecules (=\> lowering migration of leucocytes)** **reduces the numbers of B and T lymphocytes in the peripheral blood** of horses important for allergic reactions: **suppress TH1 responses while sparing TH2 responses**

Answer 74

= fungal derivative, major immunosuppressive agent for allograft survival. **selectively inhibits proliferation, cytotoxicity, and lymphokine production of T cells by binding to intracellular proteins known as immunophilins and interfering with signaling pathways that are important for clonal expansion of lymphocytes.** CAVE toxic to the kidneys and other organs. f.e. used for local treatment of keratitis and uveitis

Answer 75

**azathioprine** and **cyclophosphamide**, interfere with DNA synthesis and act primarily on dividing cells. This activity is useful for treatment of cancer and for suppression of dividing lymphocytes. f. e. Cyclophosphamide + prednisolone as chemotherapeutic protocol to achieve remission of thoracic lymphoma in a horse. f. e. used to treat immune-mediated hemolytic anemia or thrombocytopenia with success in some cases

Answer 76

**Interferon-α**. antiviral and immunostimulant properties, and oral administration of interferon-α has been shown to reduce inflammatory airway disease in racehorses. **Granulocyte Colony-Stimulating Factor**. G-CSF treatment in neonatal foals results in a sustained, dose-dependent increase in neutrophil count and a left shift, by increasing neutrophil production in the bone marrow and shortening the time to release into the circulation while the half-life remains unchanged at 8 hours.

Answer 77

**Granulocytes:** Neutrophils, Eosinophils, Basophils =\> 4-5hrs in blood, 4-5 days in the tissue (with serious infection - couple of hours), Phagen; **Monocytes:** 10-12 hours in blood =\> tissue macrophages, in tissue for months **Lymphocytes:** life span of months or years, stay in lymph and blood system

Answer 78

stimulation of the granulocytic and monocytic progenitor cells in the bone marrow --\> takes 3-4 days for newly formed granulocytes and monocytes to leave the marow area