Reply code `220` is used by the server as the first message when it agrees to interact with the client. Reply code `221` is sent by the server before closing the underlying transport connection. Reply code `250` is the standard positive reply that indicates the success of the previous command. Reply code `354` indicates that the client can start transmitting its email message. Reply code `421` is returned when there is a problem (e.g. lack of memory/disk resources) that prevents the server from accepting the transport connection.Reply codes `450` and `452` indicate that the destination mailbox is temporarily unavailable, for various reasons, while reply code `550` indicates that the mailbox does not exist or cannot be used for policy reasons.The `500` to `503` reply codes correspond to errors in the commands sent by the client. The `503` reply code would be sent by the server when the client sends commands in an incorrect order (e.g. the client tries to send an email before providing the destination address of the message).