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The skin and its appendages make up the:

  1. Circulatory system

  2. Integumentary system

  3. Digestive system

  4. Nervous system

The correct answer is: Integumentary system

The skin and its appendages, such as hair, nails, and glands, make up the integumentary system. This system is responsible for protecting the body from external threats, regulating body temperature, and excreting waste products. The circulatory system, digestive system, and nervous system do not include the skin as a major component and are responsible for different functions within the body.