CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated) systems represent the only known adaptive immune mechanism in bacteria and archaea, providing sequence-specific defense against invading mobile genetic elements (MGEs). These systems enable the capture and heritable transmission of invader-derived sequences, allowing for targeted degradation upon future encounters. This dissertation focuses on the type III-A CRISPR-Cas system from Streptococcus thermophilus (Sth), a multifunctional immune complex distinguished by its ability to bind RNA and cleave both RNA and DNA, while also generating cyclic oligoadenylates that activate auxiliary effector proteins like the RNase Csm6. In Chapter 2, I investigated which nuclease activities are essential for type III-A immunity, with particular emphasis on the RNA cleavage activity of Csm6. This study revealed an unexpected and essential role for Csm6 in the targeted degradation of invader RNA, which challenges existing models of its cleavage specificity and contributions to CRISPR defense. Chapter 3 shifts focus from CRISPR function to CRISPR inhibition, identifying five novel anti-CRISPR (Acr) proteins encoded by Sth-infecting phages. These Acrs were localized within a variable genomic region, suggesting a phage-encoded hotspot for CRISPR evasion mechanisms. In Chapter 4, I dissected the mechanism of one of these newly identified inhibitors, AcrIIIA2, a type III-A specific Acr. Structural and biochemical analyses revealed that AcrIIIA2 binds the Sth type III-A complex in combination with host enolase, forming a scaffolded interaction that prevents target RNA binding and inhibits downstream nuclease activities. This work establishes AcrIIIA2 as the second known inhibitor of type III-A systems and the first to be mechanistically and structurally characterized. Together, these dissertation studies expand our understanding of type III-A CRISPR immunity, redefine the role of Csm6 in target RNA cleavage, and provide new insights into the evolutionary arms race between bacteria and MGEs through the discovery and characterization of novel Acr proteins.