Ticks and tick borne-diseases (TBD) are major challenges to cattle production among smallholder farmers in the semiarid areas of South Africa. Nguni cattle have been reported to be resistant to ticks and TBD, however, the mechanisms responsible for the trait are not fully understood. The broad objective of this study was to determine the mechanisms of resistance to ticks in Nguni cattle reared in the semiarid areas of South Africa. Tick infestation levels, body condition scores (BCS), packed cell volumes (PCV) and the molecular prevalence of A. marginale were determined in Nguni (n = 70) and local crossbred (n = 79) cattle reared in the semiarid areas of South Africa. Relationships among skin thickness, hair length, coat score and tick counts were assessed in seven to nine month old Nguni (n = 12) and Bonsmara (n = 12) heifers. As a follow up, cutaneous hypersensitivity responses to unfed larval extracts (ULE) of the ticks Rhipicephalus decoloratus and Rhipicephalus microplus were examined in heifers to determine host immunity to the ticks. Tick counts and inflammatory cell infiltrates in skin biopsies from feeding sites of adult R. microplus ticks in nine-month-old Nguni and Bonsmara heifers were also evaluated. The molecular prevalence of A. marginale was similar in the Nguni (47.7 %) and local crossbred (52.3 %) cattle. Nguni cattle suffered less severe losses from and were more vi resilient to A. marginale infection than local crossbreds. Nguni heifers had lower coat scores, hair length and tick counts than the Bonsmara heifers. The relationship between tick counts and coat score was positive and linear in the Nguni (y = 1.90x – 0.40) and quadratic in Bonsmara (y = -7.98x2 + 12.74x - 3.12) heifers. Bonsmara cattle showed a more intense immediate reaction and no delayed hypersensitivity reaction to ULE of Rhipicephalus ticks. Nguni heifers presented a less intense immediate reaction and a delayed hypersensitivity reaction at 72 h post inoculation with ULE of Rhipicephalus ticks. Reactions to R. decoloratus ULE produced a more intense skin response at all time intervals in both breeds than that of R. microplus. Parasitized sites in Nguni heifers had higher (P < 0.05) counts of basophils, mast and mononuclear cells than those in the Bonsmara heifers. Conversely, parasitized sites in Bonsmara heifers had higher (P < 0.05) neutrophil and eosinophil counts than those in the Nguni heifers. Tick count was negatively correlated (P < 0.05) with basophil and mast cell counts. There was a positive correlation between eosinophil counts and tick counts in both breeds, and between tick counts and mononuclear cell counts in the Bonsmara breed. It was concluded that smooth and short coats, delayed type hypersensitivity and cutaneous basophil and mast cell infiltrations are responsible for increased tick resistance in the indigenous Nguni cattle breed of South Africa. / Ph.D. University of KwaZulu-Natal, Pietermaritzburg 2013.