Clinical immunology chapter 2: The Immune System of the Young Horse Flashcards

(40 cards)

1
Q

What is the paradox of neonatal vaccination?

A

The paradox involves the need for immediate protection early in life with long-term memory, challenges of the neonatal immune system, and concerns about maternal antibody interference.

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2
Q

How does the foetal immune system develop, particularly regarding lymphoid populations and immunoglobulin diversity?

A

Lymphoid populations start developing in the thymus around 80 days of gestation, and primary germinal centers in the spleen and mesenteric lymph nodes appear around day 200. B cell differentiation and Ig isotype switching become active around mid-gestation (around day 100). The foetal immune system shows a wide repertoire of Ig antigen specificity, rapidly increasing between day 100 gestation and birth.

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3
Q

How does passive transfer of immunity occur in foals, and what is the role of colostrum?

A

The epitheliochorial placenta prevents the transfer of maternal antibodies to the foetus in utero. Foals are born with non-protective amounts of endogenous serum IgM and IgG due to this barrier. Colostrum, containing innate immune proteins, cellular components, and antibodies, plays a crucial role in providing passive transfer of antibodies to the foal.

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4
Q

What are the components of colostrum that contribute to passive immunity in foals?

A

Colostrum contains complement components (C3), cytokines (TNF-alpha, IL-6), lysozyme, ferritin, antibodies, and cellular components such as maternal lymphocytes, neutrophils, macrophages, and epithelial cells.

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5
Q

How does the innate immune system of neonatal foals change over time, and what factors contribute to its activation?

A

Neonatal foals have intrinsic phagocytic and oxidative burst activities at birth. Phagocytes, particularly neutrophils, express higher levels of integrin molecule CD18 during their initial three weeks of life. Opsonization with colostrum-derived IgG is crucial for phagocytosis and bacterial killing.

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6
Q

When does endogenous immunoglobulin production begin in foals, and what is the significance of IgG4-7?

A

Endogenous immunoglobulin production begins during foetal life, with appreciable levels of serum IgM and IgG attained by 2–3 months of life. IgG4-7 is the most abundant IgG isotype in adult serum and colostrum, and its delayed production is reported in foals.

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7
Q

How does the adaptive immune system of foals develop, and when does endogenous immunoglobulin production start?

A

The adaptive immune system of foals is naïve at birth. Exposure to pathogens induces expansion of lymphocyte populations. Circulating B and T lymphocyte populations expand linearly over the first five months of life, plateauing at numbers greater than that of adult horses for a few months. Endogenous immunoglobulin production begins during foetal life.

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8
Q

What is the effect of passively transferred antibodies on endogenous immunoglobulin production in foals?

A

Some studies suggest that passively transferred antibodies may have a suppressive effect on the foal’s endogenous immunoglobulin production. However, foals are observed to generate antigen-specific immune responses in early life, even with circulating colostrum-derived antibodies.

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9
Q

How do foal peripheral blood mononuclear cells (PBMCs) demonstrate immunocompetence in the first month of life?

A

Foal PBMCs exhibit active cytokine production, including TNF-alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p35, IL-15, and IL-18. The proportion of IFN-gamma and IL-10 producing-cells increases over the first six weeks of life, with IFN-gamma expression reaching adult levels by three months old.

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10
Q

How do neonatal foals respond to experimental infection and vaccine challenges?

A

Experimental infection and vaccine challenges reveal the ability of young foals to generate antigen-specific humoral and cell-mediated immune responses. Foals are immunocompetent but may require a specific immunogenic context to generate the desired immune response.

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11
Q

Describe the immune development milestones during the foetal period, focusing on germinal centers and B cell differentiation.

A

Germinal centers in spleen and mesenteric lymph nodes develop around day 200 of gestation. Mid-gestation sees B cell differentiation, mature B cells, and Ig isotype switching in the liver, bone marrow, and spleen, with B cell transcripts expressed by day 100.

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12
Q

What are the components of colostrum that contribute to innate immunity, and how do they benefit foals?

A

Colostrum contains complement components (C3), cytokines (TNF-alpha, IL-6), lysozyme, ferritin, and antibodies. It provides essential immune proteins and cells, aiding in the passive transfer of antibodies, thereby enhancing the innate immunity of foals.

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13
Q

How does the neonatal innate immune system change regarding opsonization and chemotactic factors after colostrum ingestion?

A

Before colostrum ingestion, foal serum has fewer chemotactic and opsonic factors. After colostrum ingestion, opsonic capacity significantly increases, reaching levels comparable to adults by 3–4 weeks of life. The age-dependent increase in complement levels is observed, and administration of adult plasma enhances opsonic ability.

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14
Q

When does the bronchus-associated lymphoid tissue (BALT) develop in foals, and how does it contribute to immune development?

A

Foals lack organized lymphoid tissue in the lungs at birth, but BALT is observed by 12 weeks old. The expansion of lymphocyte populations in bronchoalveolar lavage fluid occurs gradually in the first three months, contributing to respiratory immune defense.

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15
Q

What is the significance of IgG4-7 in foals, and when is it expressed in response to Rhodococcus equi challenge?

A

IgG4-7 is the most abundant IgG isotype in adult serum and colostrum. Foals express IgG4-7 at earlier time points, with mRNA expression in neonatal spleen and peripheral blood. Serum IgG4-7 is produced in foals younger than one month when challenged with Rhodococcus equi.

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16
Q

How does the foetal immune system respond to antigen exposure, and what is the role of antigen-specific lymphocyte populations?

A

Antigen exposure induces a massive expansion of antigen-specific lymphocyte populations in early life. This leads to a 2–3 times increase in circulating lymphocytes, an increase in secondary lymphoid tissue mass, and the establishment of primed cells, contributing to immune memory.

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17
Q

Explain the temporal dynamics of circulating B and T lymphocyte populations in neonatal foals and their correlation with exposure to environmental antigens.

A

Circulating B and T lymphocyte populations in foals expand linearly over the first five months of life, plateauing at numbers greater than adult horses for a few months. The expansion correlates with exposure to environmental antigens, leading to lymphocyte activation and proliferation.

18
Q

How does the thymus, spleen, and systemic lymph nodes contribute to the immune system in foals, and what structures develop postnatally?

A

Thymus, spleen, and some systemic lymph nodes develop their structure during foetal life. Bronchus-associated lymphoid tissue (BALT) appears postnatally by 12 weeks old. Expansion of lymphocyte populations in bronchoalveolar lavage fluid occurs gradually in the first three months.

19
Q

What is the role of IgE in neonatal foals, and when does endogenous IgE production become robust?

A

Most IgE bound to neonatal basophils is of maternal origin. Endogenous production of IgE appears delayed until six months old, with robust serum IgE levels by 9–11 months, despite the decay of colostrum-derived IgE by four months.

20
Q

How do foals demonstrate immunocompetence in response to experimental infection and vaccine challenges, and is the memory response characterized?

A

Foals show the ability to generate antigen-specific humoral and cell-mediated immune responses to experimental infection and vaccine challenges. While foals are immunocompetent, the memory response has not been fully characterized yet, and further research is needed to understand the nuances.

21
Q

Describe the time frame for colostrum preparation and its significance in providing immunoglobulins to the equine neonate.

A

Colostrum preparation begins a couple of weeks pre-foaling and is active in the first 12 hours post-foaling. This timeframe is critical for efficient absorption of immunoglobulins, with absorption peaking around eight hours post-foaling and lasting, with limitations, up to 24 hours.

22
Q

What are the primary immunoglobulin isotypes found in equine colostrum, and how do they contribute to humoral protection?

A

Equine colostrum is rich primarily in IgG4/7, with small amounts of other IgG isotypes, IgM, IgA, and IgE. Colostrum-derived IgG, particularly IgG4/7, is essential for humoral protection, providing vital neutralization and opsonization properties.

23
Q

Explain the concept of Failure of Passive Transfer (FPT) in foals and its consequences.

A

FPT occurs if the foal doesn’t suckle adequate colostrum or if it can’t efficiently absorb immunoglobulins. Foals with FPT remain hypogammaglobulinemic, leading to susceptibility to infections. It is defined by a serum IgG concentration less than 800 mg/dL by 24 hours old, with partial FPT between 400 and 800 mg/dL.

24
Q

What factors contribute to the occurrence of Failure of Passive Transfer (FPT) in foals, and what is the estimated incidence?

A

FPT may result from inadequate suckling, inefficient absorption, or colostrum lacking sufficient immunoglobulins. The estimated incidence of FPT is between 10–18% of foals, with factors such as older dams, specific gravity less than 1.06, and environmental conditions influencing prevalence.

25
How is the clinical consequence of FPT manifested in foals, and what age-related challenges are associated with marginal transfer of immunoglobulins?
Foals with FPT often present with pulmonary or gastrointestinal infections or sepsis within the first month. Foals with marginal transfer may experience recurrent fevers and pneumonia until endogenous serum IgG concentration reaches protective levels (500–800 mg/dL).
26
Describe septicemia in foals, its potential routes of infection, and factors predisposing foals to sepsis.
Septicemia in foals is a life-threatening systemic condition that can arise from various routes, including respiratory, oral, and umbilical routes, as well as intrauterine placentitis. Factors like FPT may predispose foals to sepsis, but even foals with adequate passive transfer can be affected.
27
How do septic foals typically respond in terms of neutrophilia and cytokine expression, and what are the microbial causes associated with sepsis?
Septic foals respond with neutrophilia and a left shift, and cytokine expression varies, with decreased TNF-alpha, TGF-beta, and IL-4. Gram-negative bacteria like Actinobacillus equuli and Escherichia coli are implicated in the majority of septic foal cases.
28
What are the treatment approaches for septic foals, and why are opsonins crucial in managing bacterial infections?
Treatment includes intravenous plasma transfusion, broad-spectrum antibiotics, fluid therapy, and anti-inflammatory therapies. Opsonins are essential for phagocytosis and bacterial killing and are highly consumed during bacterial infection and sepsis.
29
Discuss the characteristics of Rhodococcus equi infection in foals, emphasizing the role of virulence-associated protein A (VapA) and immune responses.
Rhodococcus equi is a common cause of pneumonia in foals. VapA, a plasmid-encoded protein, enables survival in host cells. Foals typically get infected early in life, showing increased cytokine expression upon stimulation. Passive transfer or plasma transfusion is crucial for protection.
30
What challenges are associated with R. equi vaccination in foals, and how does vaccination against Equine Herpesvirus (EHV-1 and EHV-4) present unique difficulties?
Challenges include early exposure, maternal antibody interference, and concerns about the neonatal immune system. EHV-1 and EHV-4 vaccination in foals is challenging due to exposure from dams and their role as reservoirs. Different vaccine formulations and administration strategies are being explored to enhance protection.
31
Describe the paradox of neonatal vaccination, focusing on the need for immediate protection, limitations of the neonatal immune system, and concerns about maternal antibody interference.
The paradox lies in balancing immediate protection with long-term memory, potential limitations of the neonatal immune system, and concerns about maternal antibody interference. Vaccination decisions, especially against influenza, must consider the decay of colostrum-derived antibodies and vaccine-induced immunity.
32
How is vaccination against Lawsonia intracellularis approached in foals, and what are the age-dependent differences observed in response to intra-muscular vaccination with a model antigen?
Intra-rectal vaccination against Lawsonia intracellularis induces a robust immune response. Intra-muscular vaccination with a model antigen shows age-dependent differences in the quantity and quality of IgG subtypes in response.
33
What are the key considerations and challenges in live-attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccination in equine neonates?
BCG, related to R. equi, induces measurable antibody responses in neonates. Limited information exists on IFN-gamma, IL-4, and IL-10 production, with potential age-dependent differences. Ongoing research is essential to define effective administration strategies and correlates of protection.
34
What is the current state of research in neonatal vaccinology for foals, and why is ongoing research crucial?
Ongoing research focuses on refining optimal vaccine formulations and assessing protection in foals. Continuous efforts are essential to address challenges, optimize vaccination protocols, and enhance protection against various pathogens in foals.
35
Summarize the challenges and vulnerabilities associated with Rhodococcus equi infection in foals despite functional innate defenses and specific immune responses.
Young foals remain susceptible due to early exposure, environmental abundance of R. equi, and the pathogen's virulence. Prevention on endemic farms requires improved administration protocols for hyperimmune plasma.
36
How do cytokine responses of septic foals compare to that of healthy foals?
decreased gene expression of TNF-alpha, TGF-beta, and IL-4 increased expression of TLR4 comparable levels of IFN-gamma, IL-beta, IL-6, IL-8, and IL-10
37
At what age is nasal mucosal IgA detectable in foals?
1 month old
38
Deficiency in which Ig type at birth leaves foals susceptible to R. equi infection?
IgA
39
What is the half life of IgG?
30 days
40