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기상청 제공

PRRS의 모든 지식

[PRRS의 모든 지식(6)] PRRS 바이러스에 의한 면역 반응 억제

한국히프라 Swine Technical Service 노현동 수의사(hyun.noh@hipra.com)

 

모두가 양돈 현장에서 PRRS를 여러 차례 겪어 봤지만, 아직도 PRRS 컨트롤에 대한 '정답'은 없습니다. 오랜 기간 양돈농가를 괴롭혀온 만큼 PRRS에 대한 오해와 편견이 많이 쌓여있는 현실입니다. 'PRRS의 모든 지식'(총 15화)을 통해 우리 농장에 맞는 PRRS 컨트롤의 '해답'을 발견할 수 있길 기대합니다. 본 기고글은 HIPRA 본사에서 출간한 'The book for PRRS Knowledge"' 내용을 번역·정리한 것입니다.

 

 

면역 반응에 대한 이해


PRRS 바이러스에 대한 면역 반응을 이해하려면 먼저 면역계가 어떻게 작동하는지 살펴봐야 합니다. 학술적인 관점에서는 면역 반응을 선천적 면역과 후천적 면역으로 구분하는 것이 일반적이지만, 이 두 가지 면역 반응은 독립적인 과정이 아닌 밀접한 관계를 가지고 연속적으로 일어나는 과정입니다. 선천적 면역과 후천적 면역의 차이점은 반응 시간, 특이도, 기억 능력으로 요약할 수 있습니다.


선천적 면역 반응은 감염 초기에 즉각적으로 일어납니다. 이 단계에서 세포들은 병원체의 분자학적으로 보존적인 패턴에 반응하여 활성화됩니다. 후천적 면역에는 사이토카인 생성, 세포 독성 작용, 항체 형성 등의 반응들이 해당되며 선천적 면역 반응에 이어 비교적 늦게 활성화됩니다. 이 단계에서는 항원을 가공하고 제시하는 과정(antigen processing and presenting)을 통해 면역 세포들이 항원에 특이적으로 작용할 수 있는 능력을 얻게 됩니다.


활성화된 B세포와 T세포의 일부는 살아남아 후천적 면역의 기억 세포 역할을 담당합니다. 동일한 항원에 다시 노출되는 경우, 남아있던 항원 특이적인 기억 세포들이 빠르게 작동하여 면역계가 이전보다 빠르고 효율적으로 항원에 반응하도록 도와줍니다.


아래 그림은 선천적 면역과 후천적 면역 작용을 요약한 것입니다. 선천적 면역 작용에는 염증 반응과 항원 제시 과정 등 중요한 면역 과정들이 포함됩니다. 항원 가공 및 제시 과정은 정확한 후천성 면역 발달에 필수적인 과정입니다.

 


 
선천적 면역 반응


선천적 면역 시스템은 포괄적인 방식으로 병원체를 인지하고 반응하며 면역 반응의 지속 기간이 길지 않습니다. 이러한 특징에서 알 수 있듯 선천적 면역 반응은 감염 및 외부 요인에 대한 빠르고 광범위한 방어력을 제공합니다. 자연 방벽에 의한 방어와 별개로, 선천적 면역 반응에는 체액성 면역(보체, 사이토카인 등)과 세포 매개성 면역 반응이 포함됩니다. 세포 매개성 반응은 호염구(basophil), 호산구(eosinophil), 호중구(neutrophil) 등 과립구와 대식세포(macrophage), 비만세포(mast cell), 수지상세포(dendritic cell), 자연세포독성세포(natural killer cell)의 작용으로 이루어집니다.

 


선천적 면역 반응을 감염에 대한 일차 저지선으로만 생각할 수 있지만, 이 과정은 후천적 면역이 발달하기 위해 필수적인 과정이기도 합니다. 후천적 면역 반응을 담당하는 T세포들은 스스로 항원을 인지할 수 없기 때문에, 선천적 면역 과정을 통한 항원 제시 과정이 필요합니다. 항원 제시 세포(Antigen presenting cell)에는 수지상세포, 대식세포 및 B세포들이 해당됩니다. 이 중 수지상세포는 가장 강력한 T세포 활성화 작용을 가지며 선천적 면역 반응과 후천적 면역 반응을 연결하는 다리 역할을 하는 것으로 알려져 있습니다. 
 
후천적 면역 반응


항원 제시 세포들의 표면의 동시 자극 분자들과 분비된 사이토카인들은 신호 역할을 하여 보조 T세포들을 후천적 면역 반응의 핵심적 역할을 수행하는 네 가지 주요 아형(Th1, Th2, Th17, Treg)들로 분화 및 활성화시킵니다.

 


● Th1 세포: IFN-γ를 주로 분비하여 바이러스에 감염된 세포를 죽이는 세포독성 림프구들을 활성화시킴으로써 바이러스 감염을 방어하는 한편, B세포의 항체 형성을 돕는 역할을 수행하기도 합니다. IFN-γ는 대식세포를 활성화시키는 기능도 있습니다.


● Th2 세포: B세포를 ‘항체 공장’ 역할을 하는 B 형질 세포(B plasma cells)로 분화시키는 사이토카인을 분비하여 항체 형성에 핵심적인 작용을 합니다.


● Th17 세포: 호중구와 대식세포를 집결시키고 활성화시켜 세균과 진균 등 외부 병원체들을 방어에 중요한 역할을 수행합니다. Th17 세포는 바이러스 감염 시에도 유도되는 것으로 알려져 있지만, 이들이 바이러스에 대해 어떤 방어 작용을 나타내는지는 아직까지 명확히 밝혀지지 않았습니다.


● Treg 세포 : 이름에서 알 수 있듯 면역 반응을 제어(regulate immune response)하는 세포입니다. 이들은 자가 항원에 대한 면역 반응(자가 면역)이나 병원체에 대한 과도한 면역 반응을 예방합니다.
   
PRRS 바이러스에 의한 면역 억제


오랜 시간 동안 이어진 과학계의 연구에도 불구하고, PRRS 바이러스의 면역에 대한 핵심적인 내용들은 아직도 명확하게 밝혀지지 않았습니다. 하지만 이 바이러스가 여러 가지 기전을 통해 돼지의 면역 반응을 회피할 수 있다는 것은 잘 알려져 있습니다. PRRS 바이러스는 선천적 면역 반응과 후천적 면역 반응의 다양한 단계들에 강하게 간섭하여 정상적인 면역 반응을 억제합니다.

 


 
이러한 면역 반응 간섭 작용은 돼지 체내에서 PRRS 바이러스의 증식 기간이 길어지게 하여 바이러스가 다른돼지로 전파될 가능성을 높입니다.

 

아래 그림에서는 항원 제시 과정과 보조 T세포의 분화 과정에서 PRRS 바이러스에 의해 면역이 억제되는 단계들을 보여주고 있습니다. 여러 단계들에 거쳐 면역 반응을 억제하는 PRRS 바이러스는 돼지의 다른 병원체들에 비해 체액성 면역 및 세포 매개성 면역 반응을 잘 일으키지 않습니다.
 


세포 매개성 면역 반응과 중화 항체의 역가는 감염된 PRRS 바이러스에 따라 다양하게 나타나며, 감염된 개체에 따라서도 큰 차이를 보일 수 있습니다. 또한 바이러스 중화항체에 대한 감수성 및 저항성도 각각의 바이러스에 따라 다르게 나타날 수 있습니다.

 

 


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